Pigmentation Disorders

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

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 has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

The Diagnosis: Chemical Leukoderma

A clinical diagnosis of chemical leukoderma was made. In our patient, the observed linear hypopigmentation likely resulted from the prior treatment for De Quervain tenosynovitis in which an intralesional corticosteroid entered the lymphatic channel causing a linear distribution of chemical leukoderma. The hypopigmentation self-resolved at 6-month follow-up, and the patient was counseled to continue steroid injections if indicated.

Chemical leukoderma is an acquired depigmenting dermatosis that displays vitiligolike patterning. Detailed personal and family history in addition to complete physical examination are crucial given the inability to distinguish chemical leukoderma from vitiligo on histopathology. A set of clinical criteria proposed by Ghosh and Mukhopadhyay¹ includes the presence of acquired depigmented macules and patches resembling vitiligo, history of repeat exposure to certain chemical substances, hypopigmentation at the site of exposure, and/ or confettilike white macules. Three of these 4 clinical findings must be present to establish a diagnosis of chemical leukoderma. The extent of disease involvement may be graded as follows: Stage I is defined as leukoderma only at the site of contact to the offending agent. Stage II involvement is characterized by local spread beyond the exposure site via the lymphatic system. Stages IIIA and IIIB leukoderma entail hematogenous spread distant to the site of chemical exposure. Although stage IIIA leukoderma is limited to cutaneous involvement, stage IIIB findings are marked by systemic organ involvement. Stage IV disease is defined by the distant spread of hypopigmented macules and patches that continues following 1 year of strict avoidance of the causative agent.¹

The pathogenesis behind chemical leukoderma is not completely understood. Studies have suggested that individuals with certain genetic susceptibilities are predisposed to developing the condition after being exposed to chemicals with melanocytotoxic properties.^2,3 It has been proposed that the chemicals accelerate pre-existing cellular stress cascades within melanocytes to levels higher than what healthy cells can tolerate. Genetic factors can increase an individual’s total melanocytic stress or establish a lower cellular threshold for stress than what the immune system can manage.⁴ These influences culminate in an inflammatory response that results in melanocytic destruction and subsequent cutaneous hypopigmentation.

The most well-known offending chemical agents are phenol and catechol derivatives, such as hydroquinone, which is used in topical bleaching agents to treat diseases of hyperpigmentation, including melasma.² Potent topical or intralesional corticosteroids also may precipitate chemical leukoderma, most notably in individuals with darker skin tones. Hypomelanosis induced by intralesional steroids frequently occurs weeks to months after administration and commonly is observed in a stellate or linear pattern with an irregular outline.⁵ Other offending chemical agents include sulfhydryls, mercurials, arsenic, benzoyl peroxide, azelaic acid, imiquimod, chloroquine, and tyrosine kinase inhibitors.^2,5

Segmental vitiligo is characterized by unilateral hypopigmentation in a linear or blocklike distribution that does not cross the midline. However, onset of segmental vitiligo classically occurs prior to 30 years of age and frequently is related with early leukotrichia.⁶ Additionally, the hypomelanosis associated with segmental vitiligo more often presents as broad bands or patches that occasionally have a blaschkoid distribution and most commonly appear on the face.⁵ Lichen striatus is a lichenoid dermatosis that presents as asymptomatic pink or hypopigmented papules that follow the Blaschko lines, often favoring the extremities. Postinflammatory hypopigmentation also may occur as an associated sequela of resolved lichen striatus. Although the disease onset of lichen striatus may occur in adulthood, it typically appears in childhood and is triggered by factors such as trauma, hypersensitivity reactions, viral infections, and medications. Physical injuries such as trauma following surgical procedures also can lead to hypomelanosis; however, our patient denied any relevant surgical history. Progressive macular hypomelanosis is a skin condition presenting as ill-defined, nummular, hypopigmented macules or patches that commonly affects women with darker skin tones with an ethnic background from a tropical location or residing in a tropical environment.⁵ Lesions frequently appear on the trunk and rarely progress to the proximal extremities, making it an unlikely diagnosis for our patient.

In most cases of chemical leukoderma, spontaneous repigmentation often occurs within 12 months after the elimination of the offending substance; however, hypopigmented lesions may persist or continue to develop at sites distant from the initial site despite discontinuing the causative agent.1 Therapies for vitiligo, such as topical corticosteroids, topical immunosuppressants, narrowband UVB phototherapy, and psoralen plus UVA photochemotherapy, may be utilized for chemical leukoderma that does not self-resolve.

The Diagnosis: Chemical Leukoderma

A clinical diagnosis of chemical leukoderma was made. In our patient, the observed linear hypopigmentation likely resulted from the prior treatment for De Quervain tenosynovitis in which an intralesional corticosteroid entered the lymphatic channel causing a linear distribution of chemical leukoderma. The hypopigmentation self-resolved at 6-month follow-up, and the patient was counseled to continue steroid injections if indicated.

Chemical leukoderma is an acquired depigmenting dermatosis that displays vitiligolike patterning. Detailed personal and family history in addition to complete physical examination are crucial given the inability to distinguish chemical leukoderma from vitiligo on histopathology. A set of clinical criteria proposed by Ghosh and Mukhopadhyay¹ includes the presence of acquired depigmented macules and patches resembling vitiligo, history of repeat exposure to certain chemical substances, hypopigmentation at the site of exposure, and/ or confettilike white macules. Three of these 4 clinical findings must be present to establish a diagnosis of chemical leukoderma. The extent of disease involvement may be graded as follows: Stage I is defined as leukoderma only at the site of contact to the offending agent. Stage II involvement is characterized by local spread beyond the exposure site via the lymphatic system. Stages IIIA and IIIB leukoderma entail hematogenous spread distant to the site of chemical exposure. Although stage IIIA leukoderma is limited to cutaneous involvement, stage IIIB findings are marked by systemic organ involvement. Stage IV disease is defined by the distant spread of hypopigmented macules and patches that continues following 1 year of strict avoidance of the causative agent.¹

The pathogenesis behind chemical leukoderma is not completely understood. Studies have suggested that individuals with certain genetic susceptibilities are predisposed to developing the condition after being exposed to chemicals with melanocytotoxic properties.^2,3 It has been proposed that the chemicals accelerate pre-existing cellular stress cascades within melanocytes to levels higher than what healthy cells can tolerate. Genetic factors can increase an individual’s total melanocytic stress or establish a lower cellular threshold for stress than what the immune system can manage.⁴ These influences culminate in an inflammatory response that results in melanocytic destruction and subsequent cutaneous hypopigmentation.

The most well-known offending chemical agents are phenol and catechol derivatives, such as hydroquinone, which is used in topical bleaching agents to treat diseases of hyperpigmentation, including melasma.² Potent topical or intralesional corticosteroids also may precipitate chemical leukoderma, most notably in individuals with darker skin tones. Hypomelanosis induced by intralesional steroids frequently occurs weeks to months after administration and commonly is observed in a stellate or linear pattern with an irregular outline.⁵ Other offending chemical agents include sulfhydryls, mercurials, arsenic, benzoyl peroxide, azelaic acid, imiquimod, chloroquine, and tyrosine kinase inhibitors.^2,5

Segmental vitiligo is characterized by unilateral hypopigmentation in a linear or blocklike distribution that does not cross the midline. However, onset of segmental vitiligo classically occurs prior to 30 years of age and frequently is related with early leukotrichia.⁶ Additionally, the hypomelanosis associated with segmental vitiligo more often presents as broad bands or patches that occasionally have a blaschkoid distribution and most commonly appear on the face.⁵ Lichen striatus is a lichenoid dermatosis that presents as asymptomatic pink or hypopigmented papules that follow the Blaschko lines, often favoring the extremities. Postinflammatory hypopigmentation also may occur as an associated sequela of resolved lichen striatus. Although the disease onset of lichen striatus may occur in adulthood, it typically appears in childhood and is triggered by factors such as trauma, hypersensitivity reactions, viral infections, and medications. Physical injuries such as trauma following surgical procedures also can lead to hypomelanosis; however, our patient denied any relevant surgical history. Progressive macular hypomelanosis is a skin condition presenting as ill-defined, nummular, hypopigmented macules or patches that commonly affects women with darker skin tones with an ethnic background from a tropical location or residing in a tropical environment.⁵ Lesions frequently appear on the trunk and rarely progress to the proximal extremities, making it an unlikely diagnosis for our patient.

In most cases of chemical leukoderma, spontaneous repigmentation often occurs within 12 months after the elimination of the offending substance; however, hypopigmented lesions may persist or continue to develop at sites distant from the initial site despite discontinuing the causative agent.1 Therapies for vitiligo, such as topical corticosteroids, topical immunosuppressants, narrowband UVB phototherapy, and psoralen plus UVA photochemotherapy, may be utilized for chemical leukoderma that does not self-resolve.

The Diagnosis: Chemical Leukoderma

A clinical diagnosis of chemical leukoderma was made. In our patient, the observed linear hypopigmentation likely resulted from the prior treatment for De Quervain tenosynovitis in which an intralesional corticosteroid entered the lymphatic channel causing a linear distribution of chemical leukoderma. The hypopigmentation self-resolved at 6-month follow-up, and the patient was counseled to continue steroid injections if indicated.

Chemical leukoderma is an acquired depigmenting dermatosis that displays vitiligolike patterning. Detailed personal and family history in addition to complete physical examination are crucial given the inability to distinguish chemical leukoderma from vitiligo on histopathology. A set of clinical criteria proposed by Ghosh and Mukhopadhyay¹ includes the presence of acquired depigmented macules and patches resembling vitiligo, history of repeat exposure to certain chemical substances, hypopigmentation at the site of exposure, and/ or confettilike white macules. Three of these 4 clinical findings must be present to establish a diagnosis of chemical leukoderma. The extent of disease involvement may be graded as follows: Stage I is defined as leukoderma only at the site of contact to the offending agent. Stage II involvement is characterized by local spread beyond the exposure site via the lymphatic system. Stages IIIA and IIIB leukoderma entail hematogenous spread distant to the site of chemical exposure. Although stage IIIA leukoderma is limited to cutaneous involvement, stage IIIB findings are marked by systemic organ involvement. Stage IV disease is defined by the distant spread of hypopigmented macules and patches that continues following 1 year of strict avoidance of the causative agent.¹

The pathogenesis behind chemical leukoderma is not completely understood. Studies have suggested that individuals with certain genetic susceptibilities are predisposed to developing the condition after being exposed to chemicals with melanocytotoxic properties.^2,3 It has been proposed that the chemicals accelerate pre-existing cellular stress cascades within melanocytes to levels higher than what healthy cells can tolerate. Genetic factors can increase an individual’s total melanocytic stress or establish a lower cellular threshold for stress than what the immune system can manage.⁴ These influences culminate in an inflammatory response that results in melanocytic destruction and subsequent cutaneous hypopigmentation.

The most well-known offending chemical agents are phenol and catechol derivatives, such as hydroquinone, which is used in topical bleaching agents to treat diseases of hyperpigmentation, including melasma.² Potent topical or intralesional corticosteroids also may precipitate chemical leukoderma, most notably in individuals with darker skin tones. Hypomelanosis induced by intralesional steroids frequently occurs weeks to months after administration and commonly is observed in a stellate or linear pattern with an irregular outline.⁵ Other offending chemical agents include sulfhydryls, mercurials, arsenic, benzoyl peroxide, azelaic acid, imiquimod, chloroquine, and tyrosine kinase inhibitors.^2,5

Segmental vitiligo is characterized by unilateral hypopigmentation in a linear or blocklike distribution that does not cross the midline. However, onset of segmental vitiligo classically occurs prior to 30 years of age and frequently is related with early leukotrichia.⁶ Additionally, the hypomelanosis associated with segmental vitiligo more often presents as broad bands or patches that occasionally have a blaschkoid distribution and most commonly appear on the face.⁵ Lichen striatus is a lichenoid dermatosis that presents as asymptomatic pink or hypopigmented papules that follow the Blaschko lines, often favoring the extremities. Postinflammatory hypopigmentation also may occur as an associated sequela of resolved lichen striatus. Although the disease onset of lichen striatus may occur in adulthood, it typically appears in childhood and is triggered by factors such as trauma, hypersensitivity reactions, viral infections, and medications. Physical injuries such as trauma following surgical procedures also can lead to hypomelanosis; however, our patient denied any relevant surgical history. Progressive macular hypomelanosis is a skin condition presenting as ill-defined, nummular, hypopigmented macules or patches that commonly affects women with darker skin tones with an ethnic background from a tropical location or residing in a tropical environment.⁵ Lesions frequently appear on the trunk and rarely progress to the proximal extremities, making it an unlikely diagnosis for our patient.

In most cases of chemical leukoderma, spontaneous repigmentation often occurs within 12 months after the elimination of the offending substance; however, hypopigmented lesions may persist or continue to develop at sites distant from the initial site despite discontinuing the causative agent.1 Therapies for vitiligo, such as topical corticosteroids, topical immunosuppressants, narrowband UVB phototherapy, and psoralen plus UVA photochemotherapy, may be utilized for chemical leukoderma that does not self-resolve.

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

People who use skin-lightening products that contain hydroquinone may be at an increased risk for skin cancers, an analysis of records from a large research database suggests.

In the study, hydroquinone use was associated with an approximately threefold increase for skin cancer risk, coauthor Brittany Miles, a fourth-year medical student at the University of Texas Medical Branch at Galveston’s John Sealy School of Medicine, told this news organization. “The magnitude of the risk was surprising. Increased risk should be disclosed to patients considering hydroquinone treatment.”

courtesy John Sealy School of Medicine

The results of the study were presented in a poster at the annual meeting of the Society for Investigative Dermatology.

Hydroquinone (multiple brand names), a tyrosinase inhibitor used worldwide for skin lightening because of its inhibition of melanin production, was once considered “generally safe and effective” by the Food and Drug Administration, the authors wrote.

The compound’s use in over-the-counter products in the United States has been restricted based on suspicion of carcinogenicity, but few human studies have been conducted. In April, the FDA issued warning letters to 12 companies that sold hydroquinone in concentrations not generally recognized as safe and effective, because of other concerns including rashes, facial swelling, and ochronosis (skin discoloration).

Ms. Miles and her coauthor, Michael Wilkerson, MD, professor and chair of the department of dermatology at UTMB, analyzed data from TriNetX, the medical research database of anonymized medical record information from 61 million patients in 57 large health care organizations, almost all of them in the United States.

LAGUNA DESIGN/Science Photo Library/Getty Images

The researchers created two cohorts of patients aged 15 years and older with no prior diagnosis of skin cancer: one group had been treated with hydroquinone (medication code 5509 in the TriNetX system), and the other had not been exposed to the drug. Using ICD-10 codes for melanoma, nonmelanoma skin cancer, and all skin cancers, they investigated which groups of people were likely to develop these cancers.

They found that hydroquinone exposure was linked with a significant increase in melanoma (relative risk, 3.0; 95% confidence interval, 1.704-5.281; P < .0001), nonmelanoma skin cancers (RR, 3.6; 95%; CI, 2.815-4.561; P < .0001), and all reported skin cancers combined (relative risk, 3.4; 95% CI, 2.731-4.268; P < .0001)

While “the source of the data and the number of patients in the study are significant strengths,” Ms. Miles said, “the inability to determine how long and how consistently the patients used hydroquinone is likely the biggest weakness.”
 

Skin lightening is big business and more research is needed

“The U.S. market for skin-lightening agents was approximately 330 million dollars in 2021, and 330,000 prescriptions containing hydroquinone were dispensed in 2019,” Ms. Miles said.

Valencia D. Thomas, MD, professor in the department of dermatology of the University of Texas MD Anderson Cancer Center, Houston, said in an email that over-the-counter skin-lightening products containing low-concentration hydroquinone are in widespread use and are commonly used in populations of color.

“Hydroquinone preparations in higher concentrations are unfortunately also available in the United States,” added Dr. Thomas, who was not involved in the study and referred to the FDA warning letter issued in April.

Only one hydroquinone-containing medication – Tri-Luma at 4% concentration, used to treat melasma – is currently FDA-approved, she said.

The data in the study do not show an increased risk for skin cancer with hydroquinone exposure, but do show “an increased risk of cancer in the TriNetX medication code 5509 hydroquinone exposure group, which does not prove causation,” Dr. Thomas commented.

“Because ‘hydroquinone exposure’ is not defined, it is unclear how TriNetX identified the hydroquinone exposure cohort,” she noted. “Does ‘exposure’ count prescriptions written and potentially not used, the use of hydroquinone products of high concentration not approved by the FDA, or the use of over-the-counter hydroquinone products?

“The strength of this study is its size,” Dr. Thomas acknowledged. “This study is a wonderful starting point to further investigate the ‘hydroquinone exposure’ cohort to determine if hydroquinone is a driver of cancer, or if hydroquinone is itself a confounder.”

These results highlight the need to examine the social determinants of health that may explain increased risk for cancer, including race, geography, and poverty, she added.

“Given the global consumption of hydroquinone, multinational collaboration investigating hydroquinone and cancer data will likely be needed to provide insight into this continuing question,” Dr. Thomas advised.

Christiane Querfeld, MD, PhD, associate professor of dermatology and dermatopathology at City of Hope in Duarte, Calif., agreed that the occurrence of skin cancer following use of hydroquinone is largely understudied.

Courtesy City of Hope

“The findings have a huge impact on how we counsel and monitor future patients,” Dr. Querfeld, who also was not involved in the study, said in an email. “There may be a trade-off at the start of treatment: Get rid of melasma but develop a skin cancer or melanoma with potentially severe outcomes.

“It remains to be seen if there is a higher incidence of skin cancer following use of hydroquinone or other voluntary bleaching and depigmentation remedies in ethnic groups such as African American or Hispanic patient populations, who have historically been at low risk of developing skin cancer,” she added. “It also remains to be seen if increased risk is due to direct effects or to indirect effects on already-photodamaged skin.

“These data are critical, and I am sure this will open further investigations to study effects in more detail,” Dr. Querfeld said.

The study authors, Dr. Thomas, and Dr. Querfeld reported no relevant financial relationships. The study did not receive external funding.

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

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

PORTLAND, ORE. – For those who hesitate to prescribe Janus kinase inhibitors for patients with moderate to severe atopic dermatitis (AD) because of the boxed warnings on currently approved agents, it’s time to reconsider, according to Andrew Blauvelt, MD, MBA.

“In dermatology, you need to know about JAK inhibitors, and you need to know how to use them,” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the annual meeting of the Pacific Dermatologic Association. “Making the choice, ‘I’m not going to use those drugs because of safety concerns,’ may be okay in 2022, but we are going to be getting a lot more indications for these drugs. So instead of avoiding JAK inhibitors, I would say try to learn [about] them, understand them, and get your messaging out on safety.”

It’s difficult to imagine a clinician-researcher who has more experience with the use of biologics and JAK inhibitors in AD than Dr. Blauvelt, who has been the international investigator on several important trials of treatments that include dupilumab, tralokinumab, abrocitinib, and upadacitinib for AD such as CHRONOS, ECZTEND, JADE REGIMEN, and HEADS UP. At the meeting, he discussed his clinical approach to selecting systemic agents for AD and shared prescribing tips. He began by noting that the approval of dupilumab for moderate to severe AD in 2017 ushered in a new era of treating the disease systemically.

“When it was approved, experts went right to dupilumab if they could, and avoided the use of cyclosporine or methotrexate,” said Dr. Blauvelt, who is also an elected member of the American Society for Clinical Investigation and the International Eczema Council. “I still think that dupilumab is a great agent to start with. We’ve had a bit of difficulty improving upon it.”

Following dupilumab’s approval, three other systemic options became available for patients with moderate to severe AD: the human IgG4 monoclonal antibody tralokinumab that binds to interleukin-13, which is administered subcutaneously; and, more recently, the oral JAK inhibitors abrocitinib and upadacitinib, approved in January for moderate to severe AD.

“I’m a big fan of JAK inhibitors because I think they offer things that biologic and topical therapies can’t offer,” Dr. Blauvelt said. “Patients like the pills versus shots. They also like the speed; JAK inhibitors work faster than dupilumab and tralokinumab. So, if you have a patient with bad AD who wants to get better quickly, that would be a reason to choose a JAK inhibitor over a biologic if you can.”

When Dr. Blauvelt has asked AD clinical trial participants if they’d rather be treated with a biologic agent or with a JAK inhibitor, about half choose one over the other.

“Patients who shy away from the safety issues would choose the biologic trial while the ones who wanted the fast relief would choose the JAK trial,” he said. “But if you present both options and the patients prefer a pill, I think the JAK inhibitors do better with a rapid control of inflammation as well as pruritus – the latter within 2 days of taking the pills.”

When counseling patients initiating a JAK inhibitor, Dr. Blauvelt mentioned three advantages, compared with biologics: the pill formulation, the rapidity of response in pruritus control, and better efficacy. “The downside is the safety,” he said. “Safety is the elephant in the room for the JAK inhibitors.”

The risks listed in the boxed warning in the labeling for JAK inhibitors include: an increased risk of serious bacterial, fungal, and opportunistic infections such as TB; a higher rate of all-cause mortality, including cardiovascular death; a higher rate of MACE (major adverse cardiovascular events, defined as cardiovascular death, MI, and stroke); the potential for malignancy, including lymphoma; and the potential for thrombosis, including an increased incidence of pulmonary embolism (PE).

“Risk of thrombosis seems to be a class effect for all JAK inhibitors,” Dr. Blauvelt said. “As far as I know, it’s idiosyncratic. For nearly all the DVT [deep vein thrombosis] cases that have been reported, patients had baseline risk factors for DVT and PE, which are obesity, smoking, and use of oral contraceptives.”

Dr. Blauvelt pointed out that the boxed warning related to mortality, malignancies, and MACE stemmed from a long-term trial of the JAK inhibitor tofacitinib in RA patients. “Those patients had to be at least 50 years old, 75% of them were on concomitant methotrexate and/or prednisone, and they had to have at least one cardiac risk factor to get into the trial,” he said.

“I’m not saying those things can’t happen in dermatology patients, but if you look at the safety data of JAK inhibitors in the AD studies and in the alopecia areata studies, we are seeing a few cases of these things here and there, but not major signals,” he said. To date, “they look safer in dermatologic diseases compared to tofacitinib in RA data in older populations.”

He emphasized the importance of discussing each of the risks in the boxed warning with patients who are candidates for JAK inhibitor therapy.

Dr. Blauvelt likened the lab monitoring required for JAK inhibitors to that required for methotrexate. This means ordering at baseline, a CBC with differential, a chem-20, a lipid panel, and a QuantiFERON-TB Gold test. The JAK inhibitor labels do not include information on the frequency of monitoring, “but I have a distinct opinion on this because of my blood test monitoring experience in the trials for many years,” he said.

“I think it’s good to do follow-up testing at 1 month, then every 3 months in the first year. In my experience, the people who drop blood cell counts or increase their lipids tend to do it in the first year.”

After 1 year of treatment, he continued, follow-up testing once every 6 months is reasonable. “If CPK [creatine phosphokinase] goes up, I don’t worry about it; it’s not clinically relevant. There is no recommendation for CPK monitoring, so if you’re getting that on your chem-20, I’d say don’t worry about it.”

Dr. Blauvelt reported that he is an investigator and a scientific adviser for several pharmaceutical companies developing treatments for AD, including companies that are evaluating or marketing JAK inhibitors for AD, including AbbVie, Incyte, and Pfizer, as well as dupilumab’s joint developers Sanofi and Regeneron.

For the first time, patients with vitiligo who have long lived with patches of skin that are without pigment can now have even skin tones on their faces and other bodily regions with a Food and Drug Administration–approved, easy-to-use topical treatment.

In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase (JAK) inhibitor, became the first repigmentation treatment approved by the FDA for nonsegmental vitiligo, the most common form of the disease.

Topical ruxolitinib was first approved in September 2021 for atopic dermatitis, and dermatologists are already writing prescriptions for its new vitiligo indication.

“The FDA approval of ruxolitinib for repigmentation of vitiligo is historic and groundbreaking,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

The news brings hope to patients 12 years and older who suffer from the psychosocial effects of the disease, which is estimated to affect 1.9 million to 2.8 million adults in the United States.

The announcement followed FDA approval a month earlier of another dermatologic milestone – an oral JAK inhibitor, baricitinib, which became the first treatment for patients with alopecia areata.

For Dr. Desai, the ruxolitinib news is personal. His brother, also a physician, has lived a lifetime with vitiligo. His family experience, Dr. Desai said, showed him “what a disease like this can do to a person psychologically.”

Dr. Desai said his early exposure helped lead to his own decision to dedicate his career to pigmentary diseases.

His brother won’t personally benefit from the cream because his skin has been completely depigmented and repigmentation is not of interest to him, Dr. Desai said. But both brothers are excited as physicians. “It’s really quite an emotional moment,” he said.

Getting the news to patients

As dermatologists introduce the topical treatment to patients, common questions center on why this cream is different and whether it is safe.

David Rosmarin, MD, vice chair of research and education, department of dermatology, Tufts Medical Center, Boston, led the Topical Ruxolitinib Evaluation in Vitiligo Study 1 and 2 (TruE-V1, TruE-V2), conducted in North America and Europe.

He summarized some key findings.

“If patients have involvement on the face, trunk, or extremities, the data show that about half the patients at 52 weeks will get half or more of their pigment back,” he said in an interview. Results for the face alone are even better. “Half the patients will get 75% or more pigment back in the face,” Dr. Rosmarin said.

In addition, analysis of subgroups shows benefit for all patients. “Patients seem to respond similarly well across all subgroups – across gender, sex, age, ethnicity, and race,” Dr. Rosmarin said.

However, anatomic region matters, he pointed out. Skin of the head and neck responds the best, followed by skin of the trunk and extremities. The hands and feet are the most difficult to repigment because there are few hair follicles, which help enable repigmentation.

He added that it’s important to understand patients’ goals, and dermatologists shouldn’t assume that all who have vitiligo will want to undergo repigmentation. They may be interested in the new treatment but may not want it for themselves, he explained.

Explaining risks

Patients may ask about the boxed warning on the label that lists risk of heart attack, stroke, cancer, infections, blood clots, and death. Dermatologists can explain that the warning pertains to the whole JAK class and was based on patients with rheumatoid arthritis, Dr. Rosmarin said.

He added, “We didn’t see a signal for heart attack and stroke for patients using the topical. But it’s still important to discuss the label as the FDA states it.”

There are two main side effects, Dr. Rosmarin said: acne (about 6% of treated patients get it, and it’s usually mild) and application-site reactions. “Luckily, the medication has a tendency not to sting or burn, which is not the case with some of our other treatments. It’s very well tolerated,” he said.

Patients should also know that repigmentation can take time, because initially, the immune system is directed to calm down with treatment, and then pigment must travel back to the affected sites.

Some patients may have a response in as early as 2-3 months, and others need more time, Dr. Rosmarin said.

Treatment responses among adolescents have been particularly good. Responses regarding the skin of the face have been similar to those of adults. “However, on the body, they respond even better,” Dr. Rosmarin said. “About 60% achieve 50% or more repigmentation on the whole body.”

It’s important that ruxolitinib has been approved for persons aged 12 years and older, he said, because “about half the patients will develop vitiligo by the age of 20.”

Approval and insurance coverage

FDA approval will help with reimbursement for the expensive treatment.

The label indicates that patients should not use more than one 60-g tube a week. Currently, the out-of-pocket cost for one tube can be close to $2,000, according to GoodRx.

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the Center for Eczema and Itch at Northwestern University, Chicago, said that in recent years, vitiligo patients, aware that their condition could be treated by JAK inhibitors, have been paying out of pocket at compounding pharmacies, which take oral versions of the medication and compound them into topical formulations.

Unlike baricitinib, which is used to treat severe alopecia areata, and other oral JAK inhibitors, testing for TB and hepatitis is not required for initiating treatment with ruxolitinib, so no delay is necessary, Dr. Chovatiya said.

He noted, however, that patients with vitiligo may have given up on effective care after experiencing little or no improvement with topical corticosteroids, phototherapy, or topical calcineurin inhibitors.

“They end up losing steam, are less motivated on therapy, and are lost to care,” he said.

Dermatologists, he said, may need to proactively find these patients and tell them the good news. “Now that we have really good targeted therapeutic options, it’s really up to us to figure out how to bring these people back to the clinic and educate them,” Dr. Chovatiya said.

Unanswered questions to address

Some questions are still unanswered, lead study author Dr. Rosmarin said.

Two big questions are how long people will need to continue using ruxolitinib cream and whether depigmentation will recur if people stop using it.

Another aspect of therapy being studied is whether the cream will be even more effective in combination with other treatments.

“The main combination we think about is ruxolitinib with phototherapy – a light treatment – because light could stimulate those pigment cells,” Dr. Rosmarin said,

He noted that light therapy was included in phase 2 testing and that patients did respond. “What we need and what’s planned is a larger study looking at the combination to see whether it is synergistic or not. The longer patients use the cream, the more benefit we see,” Dr. Rosmarin said.

Dr. Desai has served as an investigator and/or consultant to several companies, including Incyte. Dr. Rosmarin has received honoraria as a consultant and has received research support from Incyte, and has served as a paid speaker for Incyte, as well as other companies.. Dr. Chovatiya has served as an advisory board member, consultant, and/or investigator for companies that include Incyte.

For the first time, patients with vitiligo who have long lived with patches of skin that are without pigment can now have even skin tones on their faces and other bodily regions with a Food and Drug Administration–approved, easy-to-use topical treatment.

In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase (JAK) inhibitor, became the first repigmentation treatment approved by the FDA for nonsegmental vitiligo, the most common form of the disease.

Topical ruxolitinib was first approved in September 2021 for atopic dermatitis, and dermatologists are already writing prescriptions for its new vitiligo indication.

“The FDA approval of ruxolitinib for repigmentation of vitiligo is historic and groundbreaking,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

The news brings hope to patients 12 years and older who suffer from the psychosocial effects of the disease, which is estimated to affect 1.9 million to 2.8 million adults in the United States.

The announcement followed FDA approval a month earlier of another dermatologic milestone – an oral JAK inhibitor, baricitinib, which became the first treatment for patients with alopecia areata.

For Dr. Desai, the ruxolitinib news is personal. His brother, also a physician, has lived a lifetime with vitiligo. His family experience, Dr. Desai said, showed him “what a disease like this can do to a person psychologically.”

Dr. Desai said his early exposure helped lead to his own decision to dedicate his career to pigmentary diseases.

His brother won’t personally benefit from the cream because his skin has been completely depigmented and repigmentation is not of interest to him, Dr. Desai said. But both brothers are excited as physicians. “It’s really quite an emotional moment,” he said.

Getting the news to patients

As dermatologists introduce the topical treatment to patients, common questions center on why this cream is different and whether it is safe.

David Rosmarin, MD, vice chair of research and education, department of dermatology, Tufts Medical Center, Boston, led the Topical Ruxolitinib Evaluation in Vitiligo Study 1 and 2 (TruE-V1, TruE-V2), conducted in North America and Europe.

He summarized some key findings.

“If patients have involvement on the face, trunk, or extremities, the data show that about half the patients at 52 weeks will get half or more of their pigment back,” he said in an interview. Results for the face alone are even better. “Half the patients will get 75% or more pigment back in the face,” Dr. Rosmarin said.

In addition, analysis of subgroups shows benefit for all patients. “Patients seem to respond similarly well across all subgroups – across gender, sex, age, ethnicity, and race,” Dr. Rosmarin said.

However, anatomic region matters, he pointed out. Skin of the head and neck responds the best, followed by skin of the trunk and extremities. The hands and feet are the most difficult to repigment because there are few hair follicles, which help enable repigmentation.

He added that it’s important to understand patients’ goals, and dermatologists shouldn’t assume that all who have vitiligo will want to undergo repigmentation. They may be interested in the new treatment but may not want it for themselves, he explained.

Explaining risks

Patients may ask about the boxed warning on the label that lists risk of heart attack, stroke, cancer, infections, blood clots, and death. Dermatologists can explain that the warning pertains to the whole JAK class and was based on patients with rheumatoid arthritis, Dr. Rosmarin said.

He added, “We didn’t see a signal for heart attack and stroke for patients using the topical. But it’s still important to discuss the label as the FDA states it.”

There are two main side effects, Dr. Rosmarin said: acne (about 6% of treated patients get it, and it’s usually mild) and application-site reactions. “Luckily, the medication has a tendency not to sting or burn, which is not the case with some of our other treatments. It’s very well tolerated,” he said.

Patients should also know that repigmentation can take time, because initially, the immune system is directed to calm down with treatment, and then pigment must travel back to the affected sites.

Some patients may have a response in as early as 2-3 months, and others need more time, Dr. Rosmarin said.

Treatment responses among adolescents have been particularly good. Responses regarding the skin of the face have been similar to those of adults. “However, on the body, they respond even better,” Dr. Rosmarin said. “About 60% achieve 50% or more repigmentation on the whole body.”

It’s important that ruxolitinib has been approved for persons aged 12 years and older, he said, because “about half the patients will develop vitiligo by the age of 20.”

Approval and insurance coverage

FDA approval will help with reimbursement for the expensive treatment.

The label indicates that patients should not use more than one 60-g tube a week. Currently, the out-of-pocket cost for one tube can be close to $2,000, according to GoodRx.

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the Center for Eczema and Itch at Northwestern University, Chicago, said that in recent years, vitiligo patients, aware that their condition could be treated by JAK inhibitors, have been paying out of pocket at compounding pharmacies, which take oral versions of the medication and compound them into topical formulations.

Unlike baricitinib, which is used to treat severe alopecia areata, and other oral JAK inhibitors, testing for TB and hepatitis is not required for initiating treatment with ruxolitinib, so no delay is necessary, Dr. Chovatiya said.

He noted, however, that patients with vitiligo may have given up on effective care after experiencing little or no improvement with topical corticosteroids, phototherapy, or topical calcineurin inhibitors.

“They end up losing steam, are less motivated on therapy, and are lost to care,” he said.

Dermatologists, he said, may need to proactively find these patients and tell them the good news. “Now that we have really good targeted therapeutic options, it’s really up to us to figure out how to bring these people back to the clinic and educate them,” Dr. Chovatiya said.

Unanswered questions to address

Some questions are still unanswered, lead study author Dr. Rosmarin said.

Two big questions are how long people will need to continue using ruxolitinib cream and whether depigmentation will recur if people stop using it.

Another aspect of therapy being studied is whether the cream will be even more effective in combination with other treatments.

“The main combination we think about is ruxolitinib with phototherapy – a light treatment – because light could stimulate those pigment cells,” Dr. Rosmarin said,

He noted that light therapy was included in phase 2 testing and that patients did respond. “What we need and what’s planned is a larger study looking at the combination to see whether it is synergistic or not. The longer patients use the cream, the more benefit we see,” Dr. Rosmarin said.

Dr. Desai has served as an investigator and/or consultant to several companies, including Incyte. Dr. Rosmarin has received honoraria as a consultant and has received research support from Incyte, and has served as a paid speaker for Incyte, as well as other companies.. Dr. Chovatiya has served as an advisory board member, consultant, and/or investigator for companies that include Incyte.

For the first time, patients with vitiligo who have long lived with patches of skin that are without pigment can now have even skin tones on their faces and other bodily regions with a Food and Drug Administration–approved, easy-to-use topical treatment.

In July, a cream formulation of ruxolitinib (Opzelura), a Janus kinase (JAK) inhibitor, became the first repigmentation treatment approved by the FDA for nonsegmental vitiligo, the most common form of the disease.

Topical ruxolitinib was first approved in September 2021 for atopic dermatitis, and dermatologists are already writing prescriptions for its new vitiligo indication.

“The FDA approval of ruxolitinib for repigmentation of vitiligo is historic and groundbreaking,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

The news brings hope to patients 12 years and older who suffer from the psychosocial effects of the disease, which is estimated to affect 1.9 million to 2.8 million adults in the United States.

The announcement followed FDA approval a month earlier of another dermatologic milestone – an oral JAK inhibitor, baricitinib, which became the first treatment for patients with alopecia areata.

For Dr. Desai, the ruxolitinib news is personal. His brother, also a physician, has lived a lifetime with vitiligo. His family experience, Dr. Desai said, showed him “what a disease like this can do to a person psychologically.”

Dr. Desai said his early exposure helped lead to his own decision to dedicate his career to pigmentary diseases.

His brother won’t personally benefit from the cream because his skin has been completely depigmented and repigmentation is not of interest to him, Dr. Desai said. But both brothers are excited as physicians. “It’s really quite an emotional moment,” he said.

Getting the news to patients

As dermatologists introduce the topical treatment to patients, common questions center on why this cream is different and whether it is safe.

David Rosmarin, MD, vice chair of research and education, department of dermatology, Tufts Medical Center, Boston, led the Topical Ruxolitinib Evaluation in Vitiligo Study 1 and 2 (TruE-V1, TruE-V2), conducted in North America and Europe.

He summarized some key findings.

“If patients have involvement on the face, trunk, or extremities, the data show that about half the patients at 52 weeks will get half or more of their pigment back,” he said in an interview. Results for the face alone are even better. “Half the patients will get 75% or more pigment back in the face,” Dr. Rosmarin said.

In addition, analysis of subgroups shows benefit for all patients. “Patients seem to respond similarly well across all subgroups – across gender, sex, age, ethnicity, and race,” Dr. Rosmarin said.

However, anatomic region matters, he pointed out. Skin of the head and neck responds the best, followed by skin of the trunk and extremities. The hands and feet are the most difficult to repigment because there are few hair follicles, which help enable repigmentation.

He added that it’s important to understand patients’ goals, and dermatologists shouldn’t assume that all who have vitiligo will want to undergo repigmentation. They may be interested in the new treatment but may not want it for themselves, he explained.

Explaining risks

Patients may ask about the boxed warning on the label that lists risk of heart attack, stroke, cancer, infections, blood clots, and death. Dermatologists can explain that the warning pertains to the whole JAK class and was based on patients with rheumatoid arthritis, Dr. Rosmarin said.

He added, “We didn’t see a signal for heart attack and stroke for patients using the topical. But it’s still important to discuss the label as the FDA states it.”

There are two main side effects, Dr. Rosmarin said: acne (about 6% of treated patients get it, and it’s usually mild) and application-site reactions. “Luckily, the medication has a tendency not to sting or burn, which is not the case with some of our other treatments. It’s very well tolerated,” he said.

Patients should also know that repigmentation can take time, because initially, the immune system is directed to calm down with treatment, and then pigment must travel back to the affected sites.

Some patients may have a response in as early as 2-3 months, and others need more time, Dr. Rosmarin said.

Treatment responses among adolescents have been particularly good. Responses regarding the skin of the face have been similar to those of adults. “However, on the body, they respond even better,” Dr. Rosmarin said. “About 60% achieve 50% or more repigmentation on the whole body.”

It’s important that ruxolitinib has been approved for persons aged 12 years and older, he said, because “about half the patients will develop vitiligo by the age of 20.”

Approval and insurance coverage

FDA approval will help with reimbursement for the expensive treatment.

The label indicates that patients should not use more than one 60-g tube a week. Currently, the out-of-pocket cost for one tube can be close to $2,000, according to GoodRx.

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the Center for Eczema and Itch at Northwestern University, Chicago, said that in recent years, vitiligo patients, aware that their condition could be treated by JAK inhibitors, have been paying out of pocket at compounding pharmacies, which take oral versions of the medication and compound them into topical formulations.

Unlike baricitinib, which is used to treat severe alopecia areata, and other oral JAK inhibitors, testing for TB and hepatitis is not required for initiating treatment with ruxolitinib, so no delay is necessary, Dr. Chovatiya said.

He noted, however, that patients with vitiligo may have given up on effective care after experiencing little or no improvement with topical corticosteroids, phototherapy, or topical calcineurin inhibitors.

“They end up losing steam, are less motivated on therapy, and are lost to care,” he said.

Dermatologists, he said, may need to proactively find these patients and tell them the good news. “Now that we have really good targeted therapeutic options, it’s really up to us to figure out how to bring these people back to the clinic and educate them,” Dr. Chovatiya said.

Unanswered questions to address

Some questions are still unanswered, lead study author Dr. Rosmarin said.

Two big questions are how long people will need to continue using ruxolitinib cream and whether depigmentation will recur if people stop using it.

Another aspect of therapy being studied is whether the cream will be even more effective in combination with other treatments.

“The main combination we think about is ruxolitinib with phototherapy – a light treatment – because light could stimulate those pigment cells,” Dr. Rosmarin said,

He noted that light therapy was included in phase 2 testing and that patients did respond. “What we need and what’s planned is a larger study looking at the combination to see whether it is synergistic or not. The longer patients use the cream, the more benefit we see,” Dr. Rosmarin said.

Dr. Desai has served as an investigator and/or consultant to several companies, including Incyte. Dr. Rosmarin has received honoraria as a consultant and has received research support from Incyte, and has served as a paid speaker for Incyte, as well as other companies.. Dr. Chovatiya has served as an advisory board member, consultant, and/or investigator for companies that include Incyte.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

INDIANAPOLIS – Adolescents with nonsegmental vitiligo achieved substantial repigmentation with ruxolitinib cream, compared with those in a vehicle group at week 24, and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.

Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.

In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.

For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.

For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.

Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.

“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”

In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.

“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”

Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.

However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”

Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”

Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Adolescents with nonsegmental vitiligo achieved substantial repigmentation with ruxolitinib cream, compared with those in a vehicle group at week 24, and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.

Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.

In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.

For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.

For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.

Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.

“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”

In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.

“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”

Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.

However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”

Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”

Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Adolescents with nonsegmental vitiligo achieved substantial repigmentation with ruxolitinib cream, compared with those in a vehicle group at week 24, and a higher proportion responded at week 52, results from a pooled analysis of phase 3 data showed.

Currently, there is no treatment approved by the Food and Drug Administration to repigment patients with vitiligo, but the cream formulation of the Janus kinase inhibitor ruxolitinib was shown to be effective and have a favorable safety profile in patients aged 12 years and up in the phase 3 clinical trials, TRuE-V1 and TruE-V2. “We know that about half of patients will develop vitiligo by the age of 20, so there is a significant need to have treatments available for the pediatric population,” lead study author David Rosmarin, MD, told this news organization in advance of the annual meeting of the Society for Pediatric Dermatology.

In September 2021, topical ruxolitinib (Opzelura) was approved by the FDA for treating atopic dermatitis in nonimmunocompromised patients aged 12 years and older. The manufacturer, Incyte, has submitted an application for approval to the agency for treating vitiligo in patients ages 12 years and older based on 24-week results; the FDA is expected to make a decision by July 18.

For the current study, presented during a poster session at the meeting, Dr. Rosmarin, of the department of dermatology at Tufts Medical Center, Boston, and colleagues pooled efficacy and safety data for adolescent patients aged 12-17 years from the TRuE-V studies, which enrolled patients 12 years of age and older diagnosed with nonsegmental vitiligo with depigmentation covering up to 10% of total body surface area (BSA), including facial and total Vitiligo Area Scoring Index (F-VASI/T-VASI) scores of ≥ 0.5/≥ 3. Investigators randomized patients 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through week 52. Efficacy endpoints included the proportions of patients who achieved at least 75%, 50%, and 90% improvement from baseline in F-VASI scores (F-VASI75, F-VASI50, F-VASI90); the proportion of patients who achieved at least a 50% improvement from baseline in T-VASI (T-VASI50); the proportion of patients who achieved a Vitiligo Noticeability Scale (VNS) rating of 4 or 5; and percentage change from baseline in facial BSA (F-BSA). Safety and tolerability were also assessed.

For the pooled analysis, Dr. Rosmarin and colleagues reported results on 72 adolescents: 55 who received ruxolitinib cream and 17 who received vehicle. At week 24, 32.1% of adolescents treated with ruxolitinib cream achieved F-VASI75, compared with none of those in the vehicle group. Further, response rates at week 52 for patients who applied ruxolitinib cream from day 1 were as follows: F-VASI75, 48.0%; F-VASI50, 70.0%; F-VASI90, 24.0%; T-VASI50, 60.0%; VNS score of 4/5, 56.0%; and F-BSA mean percentage change from baseline, –41.9%.

Efficacy at week 52 among crossover patients (after 28 weeks of ruxolitinib cream) was consistent with week 24 data in patients who applied ruxolitinib cream from day 1.

“As we know that repigmentation takes time, about half of the patients achieved the F-VASI75 at the 52-week endpoint,” said Dr. Rosmarin, who is also vice-chair for research and education at Tufts Medical Center, Boston. “Particularly remarkable is that 60% of adolescents achieved a T-VASI50 [50% or more repigmentation of the whole body at the year mark] and over half the patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark.”

In terms of safety, treatment-related adverse events occurred in 12.9% of patients treated with ruxolitinib (no information was available on the specific events). Serious adverse events occurred in 1.4% of patients; none were considered related to treatment.

“Overall, these results are quite impressive,” Dr. Rosmarin said. “While it can be very challenging to repigment patients with vitiligo, ruxolitinib cream provides an effective option which can help many of my patients.” He acknowledged certain limitations of the analysis, including the fact that the TRuE-V studies were conducted during the COVID-19 pandemic, “which may have contributed to patients being lost to follow-up. Also, the majority of the patients had skin phototypes 1-3.”

Carrie C. Coughlin, MD, who was asked to comment on the study, said that patients with vitiligo need treatment options that are well-studied and covered by insurance. “This study is a great step forward in developing medications for this underserved patient population,” said Dr. Coughlin, who directs the section of pediatric dermatology at Washington University/St. Louis Children’s Hospital.

However, she continued, “the authors mention approximately 13% of patients had a treatment-related adverse reaction, but the abstract does not delineate these reactions.” In addition, the study was limited to children who had less than or equal to 10% body surface area involvement of vitiligo, she noted, adding that “more work is needed to learn about safety of application to larger surface areas.”

Going forward, “it will be important to learn the durability of response,” said Dr. Coughlin, who is also assistant professor of dermatology at Washington University in St. Louis. “Does the vitiligo return if patients stop applying the ruxolitinib cream?”

Dr. Rosmarin disclosed that he has received honoraria as a consultant for Incyte, AbbVie, Abcuro, AltruBio, Arena, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio. He has also received research support from Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron; and has served as a paid speaker for Incyte, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance and the International Immunosuppression and Transplant Skin Cancer Collaborative.

Similar to other dermatologic conditions, barriers to early care in patients with vitiligo can exacerbate health disparities.¹ Delayed treatment of vitiligo is known to hamper successful disease stabilization and repigmentation, as therapies tend to work more effectively in early stages of the disease.²

To investigate the factors associated with treatment delays for patients with vitiligo, we conducted a retrospective chart review of 102 consecutive patients with vitiligo attending an academic outpatient clinic in Austin, Texas, over 36 months.

Methods

Our sample included 102 consecutive patients with vitiligo who attended an academic outpatient clinic in Austin, Texas, from January 2017 to January 2020. Demographic information, clinical characteristics of vitiligo, and treatment data were self-reported via a standardized questionnaire given to all patients with vitiligo and gathered from medical chart review. Patient characteristics are outlined in the Table. The delay to treatment was the time (in months) from the date the patient first noticed the lesion to the start date of first treatment. This retrospective chart review was reviewed by the University of Texas at Austin institutional review board and was determined to be exempt.

Statistical Analysis—The data were analyzed descriptively with a Wilcoxon rank sum test (type I error rate of .05).

Results

Of the 102 charts that were analyzed, 45 were females and 57 were males. More than half of the patients (54.9% [56/102]) were White. Sixteen were Asian, 13 were Hispanic non-White, 11 were Black/African American, and 4 were American Indian/Alaska Native. The median age of disease onset was 21 years, minimum age was 1 year, and maximum age was 83 years. The diagnosis of vitiligo was made by a dermatologist for 72 patients and by a physician of another specialty for 20 patients. Ten patients did not declare the specialty of the diagnosing physician.

Individuals older than 21 years when their disease started had a shorter delay to treatment than individuals who noticed their first lesion at an age younger than 21 years (median, 75 months vs 13 months; P<.01). Individuals diagnosed by a dermatologist had a shorter delay to treatment than individuals diagnosed by a physician of another specialty (median, 13 months vs 58 months; P<.05). White individuals had a shorter delay to treatment than individuals with skin of color (median, 13 months vs 31 months; P=.08), though this trend did not reach statistical significance. Individuals with 1% to 25% of body surface area (BSA) affected at time of presentation to clinic also had a shorter delay to treatment than those with a greater BSA affected (median, 13 months vs 74 months; P<.06), though this trend did not reach statistical significance. Type of vitiligo (P<.8), Fitzpatrick skin type (P<.6), and smoking status (P<.7) were not associated with differential delays.

Comment

Impact of Age on Vitiligo Treatment—Our data suggest that individuals who develop vitiligo at a younger age experience longer treatment delays compared to older individuals. Reasons for this are uncertain but could include access issues, medical decision-making agency, and younger patients not remembering being treated during their youth. Our data also could be influenced by some of the adult patients in our study first noticing their lesions many years ago when treatments for vitiligo were more limited. Nevertheless, detrimental effects on quality of life in children and adolescents with vitiligo suggest that motivating younger individuals with vitiligo to seek treatment or proactively making them aware of treatment opportunities may be beneficial.³

Diagnosis of Vitiligo by Nondermatologists—The increase in delay to treatment when a nondermatologist diagnoses vitiligo suggests that prompt initiation of treatment or referrals to dermatology by primary care providers may not routinely be occurring.⁴ Our data indicate the need to educate primary care providers on treatment opportunities for individuals with vitiligo and that early treatment generally is more effective.⁵

Impact of Race/Ethnicity on Vitiligo Treatment—Our data also show trends for longer treatment delays for individuals with skin of color. Although this did not reach statistical significance, we hope future studies will investigate this issue, especially because patients with skin of color experience more stigmatization and quality-of-life impacts by vitiligo than White patients.⁵

Impact of BSA on Vitiligo Treatment—Our data show that patients with a smaller BSA had a shorter delay to treatment than those with a greater BSA affected. This was a unique finding given it initially was hypothesized that patients with greater BSA would seek treatment earlier because of the associated increase in quality of life impact. This trend was not statistically significant, but further investigation would be helpful to analyze the reason behind treatment delays in patients with greater BSA affected.

Conclusion

The delay to treatment in our study population was correlated with the diagnosing physician’s specialty and patient age at disease onset, with trends also observed for race and BSA affected. These findings emphasize the need to investigate specific causes of barriers to early care to promote health equity among individuals with vitiligo.

Similar to other dermatologic conditions, barriers to early care in patients with vitiligo can exacerbate health disparities.¹ Delayed treatment of vitiligo is known to hamper successful disease stabilization and repigmentation, as therapies tend to work more effectively in early stages of the disease.²

To investigate the factors associated with treatment delays for patients with vitiligo, we conducted a retrospective chart review of 102 consecutive patients with vitiligo attending an academic outpatient clinic in Austin, Texas, over 36 months.

Methods

Our sample included 102 consecutive patients with vitiligo who attended an academic outpatient clinic in Austin, Texas, from January 2017 to January 2020. Demographic information, clinical characteristics of vitiligo, and treatment data were self-reported via a standardized questionnaire given to all patients with vitiligo and gathered from medical chart review. Patient characteristics are outlined in the Table. The delay to treatment was the time (in months) from the date the patient first noticed the lesion to the start date of first treatment. This retrospective chart review was reviewed by the University of Texas at Austin institutional review board and was determined to be exempt.

Statistical Analysis—The data were analyzed descriptively with a Wilcoxon rank sum test (type I error rate of .05).

Results

Of the 102 charts that were analyzed, 45 were females and 57 were males. More than half of the patients (54.9% [56/102]) were White. Sixteen were Asian, 13 were Hispanic non-White, 11 were Black/African American, and 4 were American Indian/Alaska Native. The median age of disease onset was 21 years, minimum age was 1 year, and maximum age was 83 years. The diagnosis of vitiligo was made by a dermatologist for 72 patients and by a physician of another specialty for 20 patients. Ten patients did not declare the specialty of the diagnosing physician.

Individuals older than 21 years when their disease started had a shorter delay to treatment than individuals who noticed their first lesion at an age younger than 21 years (median, 75 months vs 13 months; P<.01). Individuals diagnosed by a dermatologist had a shorter delay to treatment than individuals diagnosed by a physician of another specialty (median, 13 months vs 58 months; P<.05). White individuals had a shorter delay to treatment than individuals with skin of color (median, 13 months vs 31 months; P=.08), though this trend did not reach statistical significance. Individuals with 1% to 25% of body surface area (BSA) affected at time of presentation to clinic also had a shorter delay to treatment than those with a greater BSA affected (median, 13 months vs 74 months; P<.06), though this trend did not reach statistical significance. Type of vitiligo (P<.8), Fitzpatrick skin type (P<.6), and smoking status (P<.7) were not associated with differential delays.

Comment

Impact of Age on Vitiligo Treatment—Our data suggest that individuals who develop vitiligo at a younger age experience longer treatment delays compared to older individuals. Reasons for this are uncertain but could include access issues, medical decision-making agency, and younger patients not remembering being treated during their youth. Our data also could be influenced by some of the adult patients in our study first noticing their lesions many years ago when treatments for vitiligo were more limited. Nevertheless, detrimental effects on quality of life in children and adolescents with vitiligo suggest that motivating younger individuals with vitiligo to seek treatment or proactively making them aware of treatment opportunities may be beneficial.³

Diagnosis of Vitiligo by Nondermatologists—The increase in delay to treatment when a nondermatologist diagnoses vitiligo suggests that prompt initiation of treatment or referrals to dermatology by primary care providers may not routinely be occurring.⁴ Our data indicate the need to educate primary care providers on treatment opportunities for individuals with vitiligo and that early treatment generally is more effective.⁵

Impact of Race/Ethnicity on Vitiligo Treatment—Our data also show trends for longer treatment delays for individuals with skin of color. Although this did not reach statistical significance, we hope future studies will investigate this issue, especially because patients with skin of color experience more stigmatization and quality-of-life impacts by vitiligo than White patients.⁵

Impact of BSA on Vitiligo Treatment—Our data show that patients with a smaller BSA had a shorter delay to treatment than those with a greater BSA affected. This was a unique finding given it initially was hypothesized that patients with greater BSA would seek treatment earlier because of the associated increase in quality of life impact. This trend was not statistically significant, but further investigation would be helpful to analyze the reason behind treatment delays in patients with greater BSA affected.

Conclusion

The delay to treatment in our study population was correlated with the diagnosing physician’s specialty and patient age at disease onset, with trends also observed for race and BSA affected. These findings emphasize the need to investigate specific causes of barriers to early care to promote health equity among individuals with vitiligo.

Similar to other dermatologic conditions, barriers to early care in patients with vitiligo can exacerbate health disparities.¹ Delayed treatment of vitiligo is known to hamper successful disease stabilization and repigmentation, as therapies tend to work more effectively in early stages of the disease.²

To investigate the factors associated with treatment delays for patients with vitiligo, we conducted a retrospective chart review of 102 consecutive patients with vitiligo attending an academic outpatient clinic in Austin, Texas, over 36 months.

Methods

Our sample included 102 consecutive patients with vitiligo who attended an academic outpatient clinic in Austin, Texas, from January 2017 to January 2020. Demographic information, clinical characteristics of vitiligo, and treatment data were self-reported via a standardized questionnaire given to all patients with vitiligo and gathered from medical chart review. Patient characteristics are outlined in the Table. The delay to treatment was the time (in months) from the date the patient first noticed the lesion to the start date of first treatment. This retrospective chart review was reviewed by the University of Texas at Austin institutional review board and was determined to be exempt.

Statistical Analysis—The data were analyzed descriptively with a Wilcoxon rank sum test (type I error rate of .05).

Results

Of the 102 charts that were analyzed, 45 were females and 57 were males. More than half of the patients (54.9% [56/102]) were White. Sixteen were Asian, 13 were Hispanic non-White, 11 were Black/African American, and 4 were American Indian/Alaska Native. The median age of disease onset was 21 years, minimum age was 1 year, and maximum age was 83 years. The diagnosis of vitiligo was made by a dermatologist for 72 patients and by a physician of another specialty for 20 patients. Ten patients did not declare the specialty of the diagnosing physician.

Individuals older than 21 years when their disease started had a shorter delay to treatment than individuals who noticed their first lesion at an age younger than 21 years (median, 75 months vs 13 months; P<.01). Individuals diagnosed by a dermatologist had a shorter delay to treatment than individuals diagnosed by a physician of another specialty (median, 13 months vs 58 months; P<.05). White individuals had a shorter delay to treatment than individuals with skin of color (median, 13 months vs 31 months; P=.08), though this trend did not reach statistical significance. Individuals with 1% to 25% of body surface area (BSA) affected at time of presentation to clinic also had a shorter delay to treatment than those with a greater BSA affected (median, 13 months vs 74 months; P<.06), though this trend did not reach statistical significance. Type of vitiligo (P<.8), Fitzpatrick skin type (P<.6), and smoking status (P<.7) were not associated with differential delays.

Comment

Impact of Age on Vitiligo Treatment—Our data suggest that individuals who develop vitiligo at a younger age experience longer treatment delays compared to older individuals. Reasons for this are uncertain but could include access issues, medical decision-making agency, and younger patients not remembering being treated during their youth. Our data also could be influenced by some of the adult patients in our study first noticing their lesions many years ago when treatments for vitiligo were more limited. Nevertheless, detrimental effects on quality of life in children and adolescents with vitiligo suggest that motivating younger individuals with vitiligo to seek treatment or proactively making them aware of treatment opportunities may be beneficial.³

Diagnosis of Vitiligo by Nondermatologists—The increase in delay to treatment when a nondermatologist diagnoses vitiligo suggests that prompt initiation of treatment or referrals to dermatology by primary care providers may not routinely be occurring.⁴ Our data indicate the need to educate primary care providers on treatment opportunities for individuals with vitiligo and that early treatment generally is more effective.⁵

Impact of Race/Ethnicity on Vitiligo Treatment—Our data also show trends for longer treatment delays for individuals with skin of color. Although this did not reach statistical significance, we hope future studies will investigate this issue, especially because patients with skin of color experience more stigmatization and quality-of-life impacts by vitiligo than White patients.⁵

Impact of BSA on Vitiligo Treatment—Our data show that patients with a smaller BSA had a shorter delay to treatment than those with a greater BSA affected. This was a unique finding given it initially was hypothesized that patients with greater BSA would seek treatment earlier because of the associated increase in quality of life impact. This trend was not statistically significant, but further investigation would be helpful to analyze the reason behind treatment delays in patients with greater BSA affected.

Conclusion

The delay to treatment in our study population was correlated with the diagnosing physician’s specialty and patient age at disease onset, with trends also observed for race and BSA affected. These findings emphasize the need to investigate specific causes of barriers to early care to promote health equity among individuals with vitiligo.