Pigmentation Disorders

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

MYH9-related disorder is an autosomal-dominant disorder characterized by macrothrombocytopenia and neutrophil inclusions secondary to defective myosin-9.¹ We describe a case of lower leg hyperpigmentation secondary to hemosiderin deposition from MYH9-related disorder.

A 31-year-old woman with a history of MYH9-related disorder and mixed connective tissue disease presented to the outpatient dermatology clinic with asymptomatic brown patches on the lower legs (Figure) of 10 years’ duration. She also had epistaxis, hearing loss, renal disease, and menorrhagia secondary to MYH9-related disorder. The patient had been started on hydroxychloroquine 2 years earlier by rheumatology for mixed connective tissue disorder. A biopsy was not performed, given the risk of bleeding from thrombocytopenia. Ammonium lactate lotion was recommended for the leg patches. No further interventions were undertaken. At 6-month follow-up, hyperpigmentation on the lower legs was stable. The patient expressed no desire for cosmetic intervention.

Prior to discovery of a common gene, MYH9-related disorder was classified as 4 overlapping syndromes: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome.² More than 30 MYH9 mutations have been identified, all of which encode for myosin-9, a subunit of myosin IIA,^1,3 that is a nonmuscle myosin needed for cell movement, shape, and cytokinesis. Although most cells use myosin IIA to IIC, certain cells, such as platelets and neutrophils, use myosin IIA exclusively.

In neutrophils of patients with MYH9-related disorder, nonfunctional myosin-9 clumps to form hallmark inclusion bodies, which are seen on the peripheral blood smear. Macrothrombocytopenia, another hallmark of MYH9-related disorder, also can be seen on the peripheral smear of all affected patients. Approximately 30%of patients develop clinical manifestations of the disorder (eg, bleeding, renal failure, hearing loss, presenile cataracts). Bleeding tendency usually is mild; epistaxis and menorrhagia are the most common hematologic manifestations.⁴

We attribute the lower leg hyperpigmentation in our patient to a severe phenotype of MYH9-related disorder. In addition to hyperpigmentation, our patient had menorrhagia requiring treatment with tranexamic acid, renal failure, and hearing loss, further pointing to a more severe phenotype. Furthermore, it is likely that our patient’s hyperpigmentation was made worse by hydroxychloroquine and a coexisting diagnosis of mixed connective tissue disease, which led to a propensity for increased vessel fragility in the setting of thrombocytopenia.

The workup of suspected MYH9-related disorder includes exclusion of iron-deficiency anemia, which can increase bleeding in patients with the disorder. The presence of small red blood cells (RBCs) in microcytic anemia and large platelets of MYH9-related disorder can lead to a situation in which platelets travel near the center of the lumen of blood vessels, while RBCs travel to the periphery. This decrease in the platelet-endothelium interaction increases the risk for bleeding. Our patient’s hemoglobin level was within reference range, without evidence of iron-deficiency anemia. Correction of iron-deficiency anemia, if applicable, can prevent bleeding brought on by the mechanism of decreased platelet-endothelium interaction and avoid unnecessary antiplatelet medication because of misdiagnosis based on an erroneous platelet count.

The workup of MYH9-related disorder also should include audiography, ophthalmologic examination, and renal function testing for hearing loss, cataracts, and renal disease, respectively. Referral to genetics also may be warranted.

It also is of clinical interest that automated cell counters may underestimate the count of abnormally large platelets in MYH9-related disorder, counting them as RBCs or white blood cells. The platelet count in MYH9-related disorder may be underestimated by 4-fold or greater.^4-7

Treatment of leg hyperpigmentation can prove challenging, given the location of dermal hemosiderin. Topical therapy likely is ineffective. Lasers and intense pulsed light therapy are treatment modalities to consider for the hyperpigmentation of MYH9-related disorder. There have been reports of improved cosmesis in dermal hemosiderin depositional disorders, such as venous stasis.⁴ Our patient was given ammonium lactate lotion to thicken collagen, possibly preventing future bleeding episodes.

To the Editor:

MYH9-related disorder is an autosomal-dominant disorder characterized by macrothrombocytopenia and neutrophil inclusions secondary to defective myosin-9.¹ We describe a case of lower leg hyperpigmentation secondary to hemosiderin deposition from MYH9-related disorder.

A 31-year-old woman with a history of MYH9-related disorder and mixed connective tissue disease presented to the outpatient dermatology clinic with asymptomatic brown patches on the lower legs (Figure) of 10 years’ duration. She also had epistaxis, hearing loss, renal disease, and menorrhagia secondary to MYH9-related disorder. The patient had been started on hydroxychloroquine 2 years earlier by rheumatology for mixed connective tissue disorder. A biopsy was not performed, given the risk of bleeding from thrombocytopenia. Ammonium lactate lotion was recommended for the leg patches. No further interventions were undertaken. At 6-month follow-up, hyperpigmentation on the lower legs was stable. The patient expressed no desire for cosmetic intervention.

Prior to discovery of a common gene, MYH9-related disorder was classified as 4 overlapping syndromes: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome.² More than 30 MYH9 mutations have been identified, all of which encode for myosin-9, a subunit of myosin IIA,^1,3 that is a nonmuscle myosin needed for cell movement, shape, and cytokinesis. Although most cells use myosin IIA to IIC, certain cells, such as platelets and neutrophils, use myosin IIA exclusively.

In neutrophils of patients with MYH9-related disorder, nonfunctional myosin-9 clumps to form hallmark inclusion bodies, which are seen on the peripheral blood smear. Macrothrombocytopenia, another hallmark of MYH9-related disorder, also can be seen on the peripheral smear of all affected patients. Approximately 30%of patients develop clinical manifestations of the disorder (eg, bleeding, renal failure, hearing loss, presenile cataracts). Bleeding tendency usually is mild; epistaxis and menorrhagia are the most common hematologic manifestations.⁴

We attribute the lower leg hyperpigmentation in our patient to a severe phenotype of MYH9-related disorder. In addition to hyperpigmentation, our patient had menorrhagia requiring treatment with tranexamic acid, renal failure, and hearing loss, further pointing to a more severe phenotype. Furthermore, it is likely that our patient’s hyperpigmentation was made worse by hydroxychloroquine and a coexisting diagnosis of mixed connective tissue disease, which led to a propensity for increased vessel fragility in the setting of thrombocytopenia.

The workup of suspected MYH9-related disorder includes exclusion of iron-deficiency anemia, which can increase bleeding in patients with the disorder. The presence of small red blood cells (RBCs) in microcytic anemia and large platelets of MYH9-related disorder can lead to a situation in which platelets travel near the center of the lumen of blood vessels, while RBCs travel to the periphery. This decrease in the platelet-endothelium interaction increases the risk for bleeding. Our patient’s hemoglobin level was within reference range, without evidence of iron-deficiency anemia. Correction of iron-deficiency anemia, if applicable, can prevent bleeding brought on by the mechanism of decreased platelet-endothelium interaction and avoid unnecessary antiplatelet medication because of misdiagnosis based on an erroneous platelet count.

The workup of MYH9-related disorder also should include audiography, ophthalmologic examination, and renal function testing for hearing loss, cataracts, and renal disease, respectively. Referral to genetics also may be warranted.

It also is of clinical interest that automated cell counters may underestimate the count of abnormally large platelets in MYH9-related disorder, counting them as RBCs or white blood cells. The platelet count in MYH9-related disorder may be underestimated by 4-fold or greater.^4-7

Treatment of leg hyperpigmentation can prove challenging, given the location of dermal hemosiderin. Topical therapy likely is ineffective. Lasers and intense pulsed light therapy are treatment modalities to consider for the hyperpigmentation of MYH9-related disorder. There have been reports of improved cosmesis in dermal hemosiderin depositional disorders, such as venous stasis.⁴ Our patient was given ammonium lactate lotion to thicken collagen, possibly preventing future bleeding episodes.

To the Editor:

MYH9-related disorder is an autosomal-dominant disorder characterized by macrothrombocytopenia and neutrophil inclusions secondary to defective myosin-9.¹ We describe a case of lower leg hyperpigmentation secondary to hemosiderin deposition from MYH9-related disorder.

A 31-year-old woman with a history of MYH9-related disorder and mixed connective tissue disease presented to the outpatient dermatology clinic with asymptomatic brown patches on the lower legs (Figure) of 10 years’ duration. She also had epistaxis, hearing loss, renal disease, and menorrhagia secondary to MYH9-related disorder. The patient had been started on hydroxychloroquine 2 years earlier by rheumatology for mixed connective tissue disorder. A biopsy was not performed, given the risk of bleeding from thrombocytopenia. Ammonium lactate lotion was recommended for the leg patches. No further interventions were undertaken. At 6-month follow-up, hyperpigmentation on the lower legs was stable. The patient expressed no desire for cosmetic intervention.

Prior to discovery of a common gene, MYH9-related disorder was classified as 4 overlapping syndromes: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome.² More than 30 MYH9 mutations have been identified, all of which encode for myosin-9, a subunit of myosin IIA,^1,3 that is a nonmuscle myosin needed for cell movement, shape, and cytokinesis. Although most cells use myosin IIA to IIC, certain cells, such as platelets and neutrophils, use myosin IIA exclusively.

In neutrophils of patients with MYH9-related disorder, nonfunctional myosin-9 clumps to form hallmark inclusion bodies, which are seen on the peripheral blood smear. Macrothrombocytopenia, another hallmark of MYH9-related disorder, also can be seen on the peripheral smear of all affected patients. Approximately 30%of patients develop clinical manifestations of the disorder (eg, bleeding, renal failure, hearing loss, presenile cataracts). Bleeding tendency usually is mild; epistaxis and menorrhagia are the most common hematologic manifestations.⁴

We attribute the lower leg hyperpigmentation in our patient to a severe phenotype of MYH9-related disorder. In addition to hyperpigmentation, our patient had menorrhagia requiring treatment with tranexamic acid, renal failure, and hearing loss, further pointing to a more severe phenotype. Furthermore, it is likely that our patient’s hyperpigmentation was made worse by hydroxychloroquine and a coexisting diagnosis of mixed connective tissue disease, which led to a propensity for increased vessel fragility in the setting of thrombocytopenia.

The workup of suspected MYH9-related disorder includes exclusion of iron-deficiency anemia, which can increase bleeding in patients with the disorder. The presence of small red blood cells (RBCs) in microcytic anemia and large platelets of MYH9-related disorder can lead to a situation in which platelets travel near the center of the lumen of blood vessels, while RBCs travel to the periphery. This decrease in the platelet-endothelium interaction increases the risk for bleeding. Our patient’s hemoglobin level was within reference range, without evidence of iron-deficiency anemia. Correction of iron-deficiency anemia, if applicable, can prevent bleeding brought on by the mechanism of decreased platelet-endothelium interaction and avoid unnecessary antiplatelet medication because of misdiagnosis based on an erroneous platelet count.

The workup of MYH9-related disorder also should include audiography, ophthalmologic examination, and renal function testing for hearing loss, cataracts, and renal disease, respectively. Referral to genetics also may be warranted.

It also is of clinical interest that automated cell counters may underestimate the count of abnormally large platelets in MYH9-related disorder, counting them as RBCs or white blood cells. The platelet count in MYH9-related disorder may be underestimated by 4-fold or greater.^4-7

Treatment of leg hyperpigmentation can prove challenging, given the location of dermal hemosiderin. Topical therapy likely is ineffective. Lasers and intense pulsed light therapy are treatment modalities to consider for the hyperpigmentation of MYH9-related disorder. There have been reports of improved cosmesis in dermal hemosiderin depositional disorders, such as venous stasis.⁴ Our patient was given ammonium lactate lotion to thicken collagen, possibly preventing future bleeding episodes.

Vitiligo is a chronic dermatologic condition that negatively affects quality of life (QOL), with substantial burden on the psychosocial well-being of patients.¹ There is no cure, and current treatment modalities are aimed at controlling the chronic relapsing condition.^1-3 Despite topical and cosmetic treatments for stabilization and repigmentation, vitiligo remains unpredictable.³

All genders, races, ethnicities, and socioeconomic classes are equally affected.⁴ The underlying etiology of vitiligo remains unknown to a great extent and is more poorly understood by the general public compared with other skin diseases (eg, acne).⁵ Patients with vitiligo experience social withdrawal, decreased sense of self-esteem, anxiety, depression, and suicidal ideation.^5,6 Stigmatization has the greatest impact on QOL, with strong correlations between avoidance behaviors and lesion concealment.^6-8 Although the condition is especially disfiguring for darker skin types, lighter skin types also are substantially affected, with similar overall self-reported stress.^6,7

Individuals with chronic illnesses such as vitiligo turn to online communities for health information and social support, commiserating with others who have the same condition.^9,10 Online forums are platforms for asynchronous peer-to-peer exchange of disease-related information for better management of long-term disease.¹¹ Moreover, of all available internet resources, online forum posts are the most commonly accessed source of information (91%) for patients following visits with their doctors.¹²

Qualitative research involving chronic skin conditions and the information exchanged in online forums has been conducted for patients with acne, psoriasis, and atopic dermatitis, but not for patients with vitiligo.^13-16 Although online questionnaires have been administered to patients with vitiligo, the content within online forums is not well characterized.^2,17

The purpose of this qualitative study was to evaluate the online content exchanged by individuals with vitiligo to better understand the general attitudes and help-seeking behaviors in online forums.

Methods

Study Design—This qualitative study sought to investigate health beliefs and messages about vitiligo posted by users in US-based online discussion forums. An interpretive research paradigm was utilized so that all content collected in online forums were the views expressed by individuals.^18-20 An integrated approach was used in the development of the coding manual, with pre-established major themes and subthemes as a guiding framework.^16,21,22 We adhered to an inductive grounded method by means of de novo line-by-line coding, such that we had flexibility for new subthemes to emerge throughout the duration of the entire coding process.²³

Individual posts and subsequent replies embedded within public online forums were used as the collected data source. Google was utilized as the primary search engine to identify forums pertaining to vitiligo, as 80% of US adults with chronic disease report that their inquiries for health information start with Google, Bing, or Yahoo.²⁴ The institutional review board at the Wake Forest School of Medicine (Winston-Salem, North Carolina) granted approval of the study (IRB00063073). Online forums were considered “property” of the public domain and were accessible to all, eliminating the need for written informed consent.^24-26

Search Criteria—We conducted our forum search in February 2020 with a systematic approach using predetermined phrases—online forum vitiligo support, vitiligo online message board, and vitiligo forums—which yielded more than 358,171 total results (eTable 1). Threads were identified in chronological order (from newest to oldest) based on how they appeared during each internet search, and all Google results for the respective search phrases were reviewed. Dates of selected threads ranged from 2005 to 2020. Only sites with US domains were included. Posts that either included views and understandings of vitiligo or belonged to a thread that contained a vitiligo discussion were deemed relevant for inclusion. Forums were excluded if registration or means of payment was required to view posts, if there were fewer than 2 user replies to a thread, if threads contained patient photographs, or if no posts had been made in the last 2 years (rendering the thread inactive). No social media platforms, such as Facebook, or formal online platforms, such as MyVitiligoTeam, were included in the search. A no-fee-for-access was chosen for this study, as the majority of those with a chronic condition who encounter a required paywall find the information elsewhere.²⁵

Data Analysis—A total of 39 online forums were deemed relevant to the topic of vitiligo; 9 of them met inclusion criteria (eTable 2). The messages within the forums were copied verbatim into a password-encrypted text document, and usernames in the threads were de-identified, ensuring user confidentiality.

An inductive thematic analysis was utilized to explore the views and beliefs of online forum users discussing vitiligo. One author (M.B.G.) read the extracted message threads, developed an initial codebook, and established a finalized version with the agreement of another author (A.M.B.)(eTable 3). The forums were independently coded (M.B.G. and A.M.B.) in a line-by-line manner according to the codebook. Discrepancies were documented and resolved. Data saturation was adequately achieved, such that no new themes emerged during the iterative coding process. NVivo was used for qualitative analysis.

Results

Nine forums met inclusion criteria, comprising 105 pages of text. There were 61 total discussion threads, with 382 anonymous contributing users. Most users initiated a thread by posting either a question, an advice statement, or a request for help. The psychosocial impact of the disease permeated multiple domains,including personal relationships and daily life. Several threads discussed treatment, including effective camouflage and makeup, as well as peer validation of physician-prescribed treatments, along with threads dedicated to “cures” or homeopathy regimens. In several instances, commercial product endorsement, testimonials, and marketing links were reposted by the same user multiple times.

Inductive thematic analysis highlighted diverse themes and subthemes related to the beliefs and perspectives of users with vitiligo or with relatives or friends with vitiligo: psychosocial impact, disease management and camouflage/concealment, alternative medicine/homeopathy/cures, interactions with the public and health care providers, and skin tone and race. Quotes from individuals were included to demonstrate themes and subthemes.

Psychosocial Impact: QOL, Sources of Support, and Coping—There was a broad range of comments on how patients cope with and view their vitiligo. Some individuals felt vitiligo made them special, and others were at peace with and accepted their condition. In contrast, others reported the disease had devastated them and interfered with relationships. Individuals shared their stories of grief and hardships through childhood and adulthood and their concerns, especially on affected visible areas or the potential for disease progression. Users were vocal about how vitiligo affected their daily routines and lives, sharing how they felt uncomfortable outside the home, no longer engaged in swimming or exposing their legs, and preferred to stay inside instead. Some users adopted a “tough love” approach to coping, sharing how they have learned to either embrace their vitiligo or “live with it.” Some examples include:

“My best advice is go with the flow, vitiligo is not the worst thing that can happen.”

“I hate my life with vitiligo yet really I feel so selfish that there is much worse suffering in the world than a few white patches.”

Other advice was very practical:

“I hope it isn’t vanity that is tearing you apart because that is only skin deep. Make a fashion statement with hats.”

Some users acknowledged and adopted the mantra that vitiligo is not a somatic condition or “physical ailment,” while others emphasized its pervasive psychological burden:

“I still deal with this psychologically . . . You must keep a positive attitude and frame of mind . . . Vitiligo will not kill you, but you do need to stay strong and keep your head up emotionally.”

“I am just really thankful that I have a disease that will not kill me or that has [not] affected me physically at all. I consider myself lucky.”

Disease Management: Treatment, Vitiligo Course, Advice-Seeking, Camouflage—The range of information discussed for treatment was highly variable. There were many accounts in which users advised others to seek professional help, namely that of a dermatologist, for a formal assessment. Many expressed frustrations with treatments and their ineffectiveness, to which the majority of users said to consult with a professional and to remain patient and hopeful/optimistic:

“The best thing to do would be to take an appointment with a dermatologist and have the discoloration checked out. That’s the only way to know whether it is vitiligo or not.”

“My way of dealing with it is to gain control by camouflage.”

“The calming effect of being in control of my vitiligo, whether with concealers, self-tan or anything else, has stopped my feelings of despair.”

Beliefs on Alternative Medicine: Homeopathy and Alternative Regimens—Although some threads started with a post asking for the best treatments, others initiated a discussion by posting “best herbal treatments for cure” or “how to cure my vitiligo,” emphasizing the beliefs and wishes for a cure for vitiligo. Alternative therapies that users endorsed included apple cider vinegar, toothpaste, vitamins, and Ayurvedic treatment, among others. Dietary plans were popular, with users claiming success with dietary alterations in stopping and preventing lesion progression. For example, individuals felt that avoidance of sugar, meat, dairy, and citrus fruits or drinks and consumption of only filtered water were crucial to preventing further lesion spread and resulted in their “cure”:

“Don’t eat chocolate, wine (made of grapes), coffee, or tea if you don’t want to have vitiligo or let it get worse. Take Vitamin B, biotin, and nuts for Vitamin E.”

Other dangerous messages pitted treatments by health professionals against beliefs in homeopathy:

“I feel that vitiligo treatment is all in your diet and vitamins. All that medicine and UV lights is a no-no . . .w ith every medicine there is a side effect. The doctors could be healing your vitiligo and severely damaging you inside and out, and you won’t know until years later.”

There was a minor presence of users advising against homeopathy and the associated misinformation and inaccurate claims on curing vitiligo, though this group was small in comparison to the number of users posting outlandish claims on cure:

“There is no cure . . . It’s where your immune system attacks your skin cells causing loss of pigmentation. The skin that has lost the pigmentation can’t be reversed.”

Interactions With the Public and Health Care Providers—Those with vitiligo encounter unique situations in public and in their daily lives. Many of the accounts shared anecdotal stories on how patients have handled the stigma and discrimination faced:

“I have had to face discrimination at school, public places, college, functions, and every new person I have met has asked me this: ‘how did this happen?’”

Those with vitiligo even stated how they wished others would deal with their condition out in public, hoping that others would directly ask what the lesions were instead of the more hurtful staring. There were many stories in which users said others feel vitiligo was contagious or “dirty” and stressed that the condition is not infectious:

“I refer to myself as ‘camo-man’ and reassure people I come into contact with that it is not contagious.”

“Once I was eating at a restaurant . . . and a little girl said to her mom, ‘Look, Mom, that lady doesn’t wash her arms, look how dirty they are.’ That just broke my heart.”

Skin Tone and Implications—The belief that vitiligo lesions are less dramatic or less anxiety provoking for individuals with lighter skin was noted by users themselves and by health care providers in certain cases. Skin tone and its impact on QOL was confusing and contentious. Some users with fair skin stated their vitiligo was “less of an annoyance” or “less obvious” compared with individuals with darker complexions. Conversely, other accounts of self-reported White users vehemently stressed the anxieties felt by depigmented lesions, despite being “already white at baseline.”

“Was told by my dermatologist (upon diagnosis) that ‘You’re lucky you’re not African American—it shows up on them much worse. You’re so fair, it doesn’t really matter.’ ”

“You didn’t say what race you are. I could imagine it has a bigger impact if you are anything other than White.”

Comment

Patients Looking for Cures—The general attitude within the forums was uplifting and encouraging, with users detailing how they respond to others in public and sharing their personal perspectives. We found a mix of information regarding disease management and treatment of vitiligo. Overall, there was uncertainty about treatments, with individuals expressing concern that their treatments were ineffective or had failed or that better alternatives would be more suitable for their condition. We found many anecdotal endorsements of homeopathic remedies for vitiligo, with users boasting that their disease had not only been cured but had never returned. Some users completely denounced these statements, while other threads seemed to revolve completely around “cure” discussions with no dissenting voices. The number of discussions related to homeopathy was concerning. Furthermore, there often were no moderators within threads to remove cure-related content, whether commercially endorsed or anecdotal. It is plausible that supplements and vitamins recommended by some physicians may be incorrectly interpreted as a “cure” in online discussions. Our findings are consistent with prior reports that forums are a platform to express dissatisfaction with treatment and the need for additional treatment options.^15,22

Concern Expressed by Health Care Providers—Prior qualitative research has described how patients with chronic dermatologic conditions believe that health care providers minimize patients’ psychological distress.^27,28 We found several accounts in which an individual had explicitly stated their provider had “belittled” the extent and impact of vitiligo when comparing skin phototypes. This suggests either that physicians underestimate the impact of vitiligo on their patients or that physicians are not expressing enough empathic concern about the impact the condition has on those affected.

Cosmetic Aspects of Vitiligo—Few clinical trials have investigated QOL and cosmetic acceptability of treatments as outcome measures.²⁹ We found several instances in which users with vitiligo had reported being dismissed as having a “cosmetic disease,” consistent with other work demonstrating the negative impact on such dismissals.²² Moreover, concealment and camouflage techniques frequently were discussed, demonstrating the relevance of cosmetic management as an important research topic.

Trustworthy Sources of Health Information—Patients still view physicians as trustworthy and a key source of health care information and advice.^30-32 Patients with vitiligo who have been directed to reliable information sources often express gratitude²² and want health professionals to remain an important source in their health information-seeking.³¹ Given the range in information discussed online, it may be valuable to invite patients to share what information they have encountered online.

Our study highlights the conflicting health information and advice shared by users in online forums, complicating an already psychologically burdensome condition. Guiding patients to credible, moderated sites and resources that are accurate, understandable, and easy to access may help dispel the conflicting messages and stories discussed in the online community.

Study Strengths and Limitations—Limitations included reporting bias and reliance on self-reported information on the diagnosis and extent of individuals’ vitiligo. Excluding social media websites and platforms from the data collection is a limitation to comprehensively assessing the topic of internet users with vitiligo. Many social media platforms direct patients and their family members to support groups and therefore may have excluded these particular individuals. Social media platforms were excluded from our research owing to the prerequisite of creating user accounts or registering as an online member. Our inclusion criteria were specific to forums that did not require registering or creating an account and were therefore freely accessible to all internet viewers. There is an inherent lack of context present in online forums, preventing data collection on individuals’ demographics and socioeconomic backgrounds. However, anonymity may have allowed individuals to express their thoughts more freely.

An integrated approach, along with our sampling method of online forums not requiring registration, allows for greater transferability and understanding of the health needs of the general public with vitiligo.

Conclusion

Individuals with vitiligo continue to seek peer psychosocial support for the physical and emotional management of their disease. Counseling those with vitiligo about cosmetic concealment options, homeopathy, and treatment scams remains paramount. Directing patients to evidence-based resources, along with providing structured sources of support, may help to improve the psychosocial burden and QOL experienced by patients with vitiligo. Connecting patients with local and national support groups moderated by physicians, such as the Global Vitiligo Foundation (https://globalvitiligofoundation.org/), may provide benefit to patients with vitiligo.

Vitiligo is a chronic dermatologic condition that negatively affects quality of life (QOL), with substantial burden on the psychosocial well-being of patients.¹ There is no cure, and current treatment modalities are aimed at controlling the chronic relapsing condition.^1-3 Despite topical and cosmetic treatments for stabilization and repigmentation, vitiligo remains unpredictable.³

All genders, races, ethnicities, and socioeconomic classes are equally affected.⁴ The underlying etiology of vitiligo remains unknown to a great extent and is more poorly understood by the general public compared with other skin diseases (eg, acne).⁵ Patients with vitiligo experience social withdrawal, decreased sense of self-esteem, anxiety, depression, and suicidal ideation.^5,6 Stigmatization has the greatest impact on QOL, with strong correlations between avoidance behaviors and lesion concealment.^6-8 Although the condition is especially disfiguring for darker skin types, lighter skin types also are substantially affected, with similar overall self-reported stress.^6,7

Individuals with chronic illnesses such as vitiligo turn to online communities for health information and social support, commiserating with others who have the same condition.^9,10 Online forums are platforms for asynchronous peer-to-peer exchange of disease-related information for better management of long-term disease.¹¹ Moreover, of all available internet resources, online forum posts are the most commonly accessed source of information (91%) for patients following visits with their doctors.¹²

Qualitative research involving chronic skin conditions and the information exchanged in online forums has been conducted for patients with acne, psoriasis, and atopic dermatitis, but not for patients with vitiligo.^13-16 Although online questionnaires have been administered to patients with vitiligo, the content within online forums is not well characterized.^2,17

The purpose of this qualitative study was to evaluate the online content exchanged by individuals with vitiligo to better understand the general attitudes and help-seeking behaviors in online forums.

Methods

Study Design—This qualitative study sought to investigate health beliefs and messages about vitiligo posted by users in US-based online discussion forums. An interpretive research paradigm was utilized so that all content collected in online forums were the views expressed by individuals.^18-20 An integrated approach was used in the development of the coding manual, with pre-established major themes and subthemes as a guiding framework.^16,21,22 We adhered to an inductive grounded method by means of de novo line-by-line coding, such that we had flexibility for new subthemes to emerge throughout the duration of the entire coding process.²³

Individual posts and subsequent replies embedded within public online forums were used as the collected data source. Google was utilized as the primary search engine to identify forums pertaining to vitiligo, as 80% of US adults with chronic disease report that their inquiries for health information start with Google, Bing, or Yahoo.²⁴ The institutional review board at the Wake Forest School of Medicine (Winston-Salem, North Carolina) granted approval of the study (IRB00063073). Online forums were considered “property” of the public domain and were accessible to all, eliminating the need for written informed consent.^24-26

Search Criteria—We conducted our forum search in February 2020 with a systematic approach using predetermined phrases—online forum vitiligo support, vitiligo online message board, and vitiligo forums—which yielded more than 358,171 total results (eTable 1). Threads were identified in chronological order (from newest to oldest) based on how they appeared during each internet search, and all Google results for the respective search phrases were reviewed. Dates of selected threads ranged from 2005 to 2020. Only sites with US domains were included. Posts that either included views and understandings of vitiligo or belonged to a thread that contained a vitiligo discussion were deemed relevant for inclusion. Forums were excluded if registration or means of payment was required to view posts, if there were fewer than 2 user replies to a thread, if threads contained patient photographs, or if no posts had been made in the last 2 years (rendering the thread inactive). No social media platforms, such as Facebook, or formal online platforms, such as MyVitiligoTeam, were included in the search. A no-fee-for-access was chosen for this study, as the majority of those with a chronic condition who encounter a required paywall find the information elsewhere.²⁵

Data Analysis—A total of 39 online forums were deemed relevant to the topic of vitiligo; 9 of them met inclusion criteria (eTable 2). The messages within the forums were copied verbatim into a password-encrypted text document, and usernames in the threads were de-identified, ensuring user confidentiality.

An inductive thematic analysis was utilized to explore the views and beliefs of online forum users discussing vitiligo. One author (M.B.G.) read the extracted message threads, developed an initial codebook, and established a finalized version with the agreement of another author (A.M.B.)(eTable 3). The forums were independently coded (M.B.G. and A.M.B.) in a line-by-line manner according to the codebook. Discrepancies were documented and resolved. Data saturation was adequately achieved, such that no new themes emerged during the iterative coding process. NVivo was used for qualitative analysis.

Results

Nine forums met inclusion criteria, comprising 105 pages of text. There were 61 total discussion threads, with 382 anonymous contributing users. Most users initiated a thread by posting either a question, an advice statement, or a request for help. The psychosocial impact of the disease permeated multiple domains,including personal relationships and daily life. Several threads discussed treatment, including effective camouflage and makeup, as well as peer validation of physician-prescribed treatments, along with threads dedicated to “cures” or homeopathy regimens. In several instances, commercial product endorsement, testimonials, and marketing links were reposted by the same user multiple times.

Inductive thematic analysis highlighted diverse themes and subthemes related to the beliefs and perspectives of users with vitiligo or with relatives or friends with vitiligo: psychosocial impact, disease management and camouflage/concealment, alternative medicine/homeopathy/cures, interactions with the public and health care providers, and skin tone and race. Quotes from individuals were included to demonstrate themes and subthemes.

Psychosocial Impact: QOL, Sources of Support, and Coping—There was a broad range of comments on how patients cope with and view their vitiligo. Some individuals felt vitiligo made them special, and others were at peace with and accepted their condition. In contrast, others reported the disease had devastated them and interfered with relationships. Individuals shared their stories of grief and hardships through childhood and adulthood and their concerns, especially on affected visible areas or the potential for disease progression. Users were vocal about how vitiligo affected their daily routines and lives, sharing how they felt uncomfortable outside the home, no longer engaged in swimming or exposing their legs, and preferred to stay inside instead. Some users adopted a “tough love” approach to coping, sharing how they have learned to either embrace their vitiligo or “live with it.” Some examples include:

“My best advice is go with the flow, vitiligo is not the worst thing that can happen.”

“I hate my life with vitiligo yet really I feel so selfish that there is much worse suffering in the world than a few white patches.”

Other advice was very practical:

“I hope it isn’t vanity that is tearing you apart because that is only skin deep. Make a fashion statement with hats.”

Some users acknowledged and adopted the mantra that vitiligo is not a somatic condition or “physical ailment,” while others emphasized its pervasive psychological burden:

“I still deal with this psychologically . . . You must keep a positive attitude and frame of mind . . . Vitiligo will not kill you, but you do need to stay strong and keep your head up emotionally.”

“I am just really thankful that I have a disease that will not kill me or that has [not] affected me physically at all. I consider myself lucky.”

Disease Management: Treatment, Vitiligo Course, Advice-Seeking, Camouflage—The range of information discussed for treatment was highly variable. There were many accounts in which users advised others to seek professional help, namely that of a dermatologist, for a formal assessment. Many expressed frustrations with treatments and their ineffectiveness, to which the majority of users said to consult with a professional and to remain patient and hopeful/optimistic:

“The best thing to do would be to take an appointment with a dermatologist and have the discoloration checked out. That’s the only way to know whether it is vitiligo or not.”

“My way of dealing with it is to gain control by camouflage.”

“The calming effect of being in control of my vitiligo, whether with concealers, self-tan or anything else, has stopped my feelings of despair.”

Beliefs on Alternative Medicine: Homeopathy and Alternative Regimens—Although some threads started with a post asking for the best treatments, others initiated a discussion by posting “best herbal treatments for cure” or “how to cure my vitiligo,” emphasizing the beliefs and wishes for a cure for vitiligo. Alternative therapies that users endorsed included apple cider vinegar, toothpaste, vitamins, and Ayurvedic treatment, among others. Dietary plans were popular, with users claiming success with dietary alterations in stopping and preventing lesion progression. For example, individuals felt that avoidance of sugar, meat, dairy, and citrus fruits or drinks and consumption of only filtered water were crucial to preventing further lesion spread and resulted in their “cure”:

“Don’t eat chocolate, wine (made of grapes), coffee, or tea if you don’t want to have vitiligo or let it get worse. Take Vitamin B, biotin, and nuts for Vitamin E.”

Other dangerous messages pitted treatments by health professionals against beliefs in homeopathy:

“I feel that vitiligo treatment is all in your diet and vitamins. All that medicine and UV lights is a no-no . . .w ith every medicine there is a side effect. The doctors could be healing your vitiligo and severely damaging you inside and out, and you won’t know until years later.”

There was a minor presence of users advising against homeopathy and the associated misinformation and inaccurate claims on curing vitiligo, though this group was small in comparison to the number of users posting outlandish claims on cure:

“There is no cure . . . It’s where your immune system attacks your skin cells causing loss of pigmentation. The skin that has lost the pigmentation can’t be reversed.”

Interactions With the Public and Health Care Providers—Those with vitiligo encounter unique situations in public and in their daily lives. Many of the accounts shared anecdotal stories on how patients have handled the stigma and discrimination faced:

“I have had to face discrimination at school, public places, college, functions, and every new person I have met has asked me this: ‘how did this happen?’”

Those with vitiligo even stated how they wished others would deal with their condition out in public, hoping that others would directly ask what the lesions were instead of the more hurtful staring. There were many stories in which users said others feel vitiligo was contagious or “dirty” and stressed that the condition is not infectious:

“I refer to myself as ‘camo-man’ and reassure people I come into contact with that it is not contagious.”

“Once I was eating at a restaurant . . . and a little girl said to her mom, ‘Look, Mom, that lady doesn’t wash her arms, look how dirty they are.’ That just broke my heart.”

Skin Tone and Implications—The belief that vitiligo lesions are less dramatic or less anxiety provoking for individuals with lighter skin was noted by users themselves and by health care providers in certain cases. Skin tone and its impact on QOL was confusing and contentious. Some users with fair skin stated their vitiligo was “less of an annoyance” or “less obvious” compared with individuals with darker complexions. Conversely, other accounts of self-reported White users vehemently stressed the anxieties felt by depigmented lesions, despite being “already white at baseline.”

“Was told by my dermatologist (upon diagnosis) that ‘You’re lucky you’re not African American—it shows up on them much worse. You’re so fair, it doesn’t really matter.’ ”

“You didn’t say what race you are. I could imagine it has a bigger impact if you are anything other than White.”

Comment

Patients Looking for Cures—The general attitude within the forums was uplifting and encouraging, with users detailing how they respond to others in public and sharing their personal perspectives. We found a mix of information regarding disease management and treatment of vitiligo. Overall, there was uncertainty about treatments, with individuals expressing concern that their treatments were ineffective or had failed or that better alternatives would be more suitable for their condition. We found many anecdotal endorsements of homeopathic remedies for vitiligo, with users boasting that their disease had not only been cured but had never returned. Some users completely denounced these statements, while other threads seemed to revolve completely around “cure” discussions with no dissenting voices. The number of discussions related to homeopathy was concerning. Furthermore, there often were no moderators within threads to remove cure-related content, whether commercially endorsed or anecdotal. It is plausible that supplements and vitamins recommended by some physicians may be incorrectly interpreted as a “cure” in online discussions. Our findings are consistent with prior reports that forums are a platform to express dissatisfaction with treatment and the need for additional treatment options.^15,22

Concern Expressed by Health Care Providers—Prior qualitative research has described how patients with chronic dermatologic conditions believe that health care providers minimize patients’ psychological distress.^27,28 We found several accounts in which an individual had explicitly stated their provider had “belittled” the extent and impact of vitiligo when comparing skin phototypes. This suggests either that physicians underestimate the impact of vitiligo on their patients or that physicians are not expressing enough empathic concern about the impact the condition has on those affected.

Cosmetic Aspects of Vitiligo—Few clinical trials have investigated QOL and cosmetic acceptability of treatments as outcome measures.²⁹ We found several instances in which users with vitiligo had reported being dismissed as having a “cosmetic disease,” consistent with other work demonstrating the negative impact on such dismissals.²² Moreover, concealment and camouflage techniques frequently were discussed, demonstrating the relevance of cosmetic management as an important research topic.

Trustworthy Sources of Health Information—Patients still view physicians as trustworthy and a key source of health care information and advice.^30-32 Patients with vitiligo who have been directed to reliable information sources often express gratitude²² and want health professionals to remain an important source in their health information-seeking.³¹ Given the range in information discussed online, it may be valuable to invite patients to share what information they have encountered online.

Our study highlights the conflicting health information and advice shared by users in online forums, complicating an already psychologically burdensome condition. Guiding patients to credible, moderated sites and resources that are accurate, understandable, and easy to access may help dispel the conflicting messages and stories discussed in the online community.

Study Strengths and Limitations—Limitations included reporting bias and reliance on self-reported information on the diagnosis and extent of individuals’ vitiligo. Excluding social media websites and platforms from the data collection is a limitation to comprehensively assessing the topic of internet users with vitiligo. Many social media platforms direct patients and their family members to support groups and therefore may have excluded these particular individuals. Social media platforms were excluded from our research owing to the prerequisite of creating user accounts or registering as an online member. Our inclusion criteria were specific to forums that did not require registering or creating an account and were therefore freely accessible to all internet viewers. There is an inherent lack of context present in online forums, preventing data collection on individuals’ demographics and socioeconomic backgrounds. However, anonymity may have allowed individuals to express their thoughts more freely.

An integrated approach, along with our sampling method of online forums not requiring registration, allows for greater transferability and understanding of the health needs of the general public with vitiligo.

Conclusion

Individuals with vitiligo continue to seek peer psychosocial support for the physical and emotional management of their disease. Counseling those with vitiligo about cosmetic concealment options, homeopathy, and treatment scams remains paramount. Directing patients to evidence-based resources, along with providing structured sources of support, may help to improve the psychosocial burden and QOL experienced by patients with vitiligo. Connecting patients with local and national support groups moderated by physicians, such as the Global Vitiligo Foundation (https://globalvitiligofoundation.org/), may provide benefit to patients with vitiligo.

Vitiligo is a chronic dermatologic condition that negatively affects quality of life (QOL), with substantial burden on the psychosocial well-being of patients.¹ There is no cure, and current treatment modalities are aimed at controlling the chronic relapsing condition.^1-3 Despite topical and cosmetic treatments for stabilization and repigmentation, vitiligo remains unpredictable.³

All genders, races, ethnicities, and socioeconomic classes are equally affected.⁴ The underlying etiology of vitiligo remains unknown to a great extent and is more poorly understood by the general public compared with other skin diseases (eg, acne).⁵ Patients with vitiligo experience social withdrawal, decreased sense of self-esteem, anxiety, depression, and suicidal ideation.^5,6 Stigmatization has the greatest impact on QOL, with strong correlations between avoidance behaviors and lesion concealment.^6-8 Although the condition is especially disfiguring for darker skin types, lighter skin types also are substantially affected, with similar overall self-reported stress.^6,7

Individuals with chronic illnesses such as vitiligo turn to online communities for health information and social support, commiserating with others who have the same condition.^9,10 Online forums are platforms for asynchronous peer-to-peer exchange of disease-related information for better management of long-term disease.¹¹ Moreover, of all available internet resources, online forum posts are the most commonly accessed source of information (91%) for patients following visits with their doctors.¹²

Qualitative research involving chronic skin conditions and the information exchanged in online forums has been conducted for patients with acne, psoriasis, and atopic dermatitis, but not for patients with vitiligo.^13-16 Although online questionnaires have been administered to patients with vitiligo, the content within online forums is not well characterized.^2,17

The purpose of this qualitative study was to evaluate the online content exchanged by individuals with vitiligo to better understand the general attitudes and help-seeking behaviors in online forums.

Methods

Study Design—This qualitative study sought to investigate health beliefs and messages about vitiligo posted by users in US-based online discussion forums. An interpretive research paradigm was utilized so that all content collected in online forums were the views expressed by individuals.^18-20 An integrated approach was used in the development of the coding manual, with pre-established major themes and subthemes as a guiding framework.^16,21,22 We adhered to an inductive grounded method by means of de novo line-by-line coding, such that we had flexibility for new subthemes to emerge throughout the duration of the entire coding process.²³

Individual posts and subsequent replies embedded within public online forums were used as the collected data source. Google was utilized as the primary search engine to identify forums pertaining to vitiligo, as 80% of US adults with chronic disease report that their inquiries for health information start with Google, Bing, or Yahoo.²⁴ The institutional review board at the Wake Forest School of Medicine (Winston-Salem, North Carolina) granted approval of the study (IRB00063073). Online forums were considered “property” of the public domain and were accessible to all, eliminating the need for written informed consent.^24-26

Search Criteria—We conducted our forum search in February 2020 with a systematic approach using predetermined phrases—online forum vitiligo support, vitiligo online message board, and vitiligo forums—which yielded more than 358,171 total results (eTable 1). Threads were identified in chronological order (from newest to oldest) based on how they appeared during each internet search, and all Google results for the respective search phrases were reviewed. Dates of selected threads ranged from 2005 to 2020. Only sites with US domains were included. Posts that either included views and understandings of vitiligo or belonged to a thread that contained a vitiligo discussion were deemed relevant for inclusion. Forums were excluded if registration or means of payment was required to view posts, if there were fewer than 2 user replies to a thread, if threads contained patient photographs, or if no posts had been made in the last 2 years (rendering the thread inactive). No social media platforms, such as Facebook, or formal online platforms, such as MyVitiligoTeam, were included in the search. A no-fee-for-access was chosen for this study, as the majority of those with a chronic condition who encounter a required paywall find the information elsewhere.²⁵

Data Analysis—A total of 39 online forums were deemed relevant to the topic of vitiligo; 9 of them met inclusion criteria (eTable 2). The messages within the forums were copied verbatim into a password-encrypted text document, and usernames in the threads were de-identified, ensuring user confidentiality.

An inductive thematic analysis was utilized to explore the views and beliefs of online forum users discussing vitiligo. One author (M.B.G.) read the extracted message threads, developed an initial codebook, and established a finalized version with the agreement of another author (A.M.B.)(eTable 3). The forums were independently coded (M.B.G. and A.M.B.) in a line-by-line manner according to the codebook. Discrepancies were documented and resolved. Data saturation was adequately achieved, such that no new themes emerged during the iterative coding process. NVivo was used for qualitative analysis.

Results

Nine forums met inclusion criteria, comprising 105 pages of text. There were 61 total discussion threads, with 382 anonymous contributing users. Most users initiated a thread by posting either a question, an advice statement, or a request for help. The psychosocial impact of the disease permeated multiple domains,including personal relationships and daily life. Several threads discussed treatment, including effective camouflage and makeup, as well as peer validation of physician-prescribed treatments, along with threads dedicated to “cures” or homeopathy regimens. In several instances, commercial product endorsement, testimonials, and marketing links were reposted by the same user multiple times.

Inductive thematic analysis highlighted diverse themes and subthemes related to the beliefs and perspectives of users with vitiligo or with relatives or friends with vitiligo: psychosocial impact, disease management and camouflage/concealment, alternative medicine/homeopathy/cures, interactions with the public and health care providers, and skin tone and race. Quotes from individuals were included to demonstrate themes and subthemes.

Psychosocial Impact: QOL, Sources of Support, and Coping—There was a broad range of comments on how patients cope with and view their vitiligo. Some individuals felt vitiligo made them special, and others were at peace with and accepted their condition. In contrast, others reported the disease had devastated them and interfered with relationships. Individuals shared their stories of grief and hardships through childhood and adulthood and their concerns, especially on affected visible areas or the potential for disease progression. Users were vocal about how vitiligo affected their daily routines and lives, sharing how they felt uncomfortable outside the home, no longer engaged in swimming or exposing their legs, and preferred to stay inside instead. Some users adopted a “tough love” approach to coping, sharing how they have learned to either embrace their vitiligo or “live with it.” Some examples include:

“My best advice is go with the flow, vitiligo is not the worst thing that can happen.”

“I hate my life with vitiligo yet really I feel so selfish that there is much worse suffering in the world than a few white patches.”

Other advice was very practical:

“I hope it isn’t vanity that is tearing you apart because that is only skin deep. Make a fashion statement with hats.”

Some users acknowledged and adopted the mantra that vitiligo is not a somatic condition or “physical ailment,” while others emphasized its pervasive psychological burden:

“I still deal with this psychologically . . . You must keep a positive attitude and frame of mind . . . Vitiligo will not kill you, but you do need to stay strong and keep your head up emotionally.”

“I am just really thankful that I have a disease that will not kill me or that has [not] affected me physically at all. I consider myself lucky.”

Disease Management: Treatment, Vitiligo Course, Advice-Seeking, Camouflage—The range of information discussed for treatment was highly variable. There were many accounts in which users advised others to seek professional help, namely that of a dermatologist, for a formal assessment. Many expressed frustrations with treatments and their ineffectiveness, to which the majority of users said to consult with a professional and to remain patient and hopeful/optimistic:

“The best thing to do would be to take an appointment with a dermatologist and have the discoloration checked out. That’s the only way to know whether it is vitiligo or not.”

“My way of dealing with it is to gain control by camouflage.”

“The calming effect of being in control of my vitiligo, whether with concealers, self-tan or anything else, has stopped my feelings of despair.”

Beliefs on Alternative Medicine: Homeopathy and Alternative Regimens—Although some threads started with a post asking for the best treatments, others initiated a discussion by posting “best herbal treatments for cure” or “how to cure my vitiligo,” emphasizing the beliefs and wishes for a cure for vitiligo. Alternative therapies that users endorsed included apple cider vinegar, toothpaste, vitamins, and Ayurvedic treatment, among others. Dietary plans were popular, with users claiming success with dietary alterations in stopping and preventing lesion progression. For example, individuals felt that avoidance of sugar, meat, dairy, and citrus fruits or drinks and consumption of only filtered water were crucial to preventing further lesion spread and resulted in their “cure”:

“Don’t eat chocolate, wine (made of grapes), coffee, or tea if you don’t want to have vitiligo or let it get worse. Take Vitamin B, biotin, and nuts for Vitamin E.”

Other dangerous messages pitted treatments by health professionals against beliefs in homeopathy:

“I feel that vitiligo treatment is all in your diet and vitamins. All that medicine and UV lights is a no-no . . .w ith every medicine there is a side effect. The doctors could be healing your vitiligo and severely damaging you inside and out, and you won’t know until years later.”

There was a minor presence of users advising against homeopathy and the associated misinformation and inaccurate claims on curing vitiligo, though this group was small in comparison to the number of users posting outlandish claims on cure:

“There is no cure . . . It’s where your immune system attacks your skin cells causing loss of pigmentation. The skin that has lost the pigmentation can’t be reversed.”

Interactions With the Public and Health Care Providers—Those with vitiligo encounter unique situations in public and in their daily lives. Many of the accounts shared anecdotal stories on how patients have handled the stigma and discrimination faced:

“I have had to face discrimination at school, public places, college, functions, and every new person I have met has asked me this: ‘how did this happen?’”

Those with vitiligo even stated how they wished others would deal with their condition out in public, hoping that others would directly ask what the lesions were instead of the more hurtful staring. There were many stories in which users said others feel vitiligo was contagious or “dirty” and stressed that the condition is not infectious:

“I refer to myself as ‘camo-man’ and reassure people I come into contact with that it is not contagious.”

“Once I was eating at a restaurant . . . and a little girl said to her mom, ‘Look, Mom, that lady doesn’t wash her arms, look how dirty they are.’ That just broke my heart.”

Skin Tone and Implications—The belief that vitiligo lesions are less dramatic or less anxiety provoking for individuals with lighter skin was noted by users themselves and by health care providers in certain cases. Skin tone and its impact on QOL was confusing and contentious. Some users with fair skin stated their vitiligo was “less of an annoyance” or “less obvious” compared with individuals with darker complexions. Conversely, other accounts of self-reported White users vehemently stressed the anxieties felt by depigmented lesions, despite being “already white at baseline.”

“Was told by my dermatologist (upon diagnosis) that ‘You’re lucky you’re not African American—it shows up on them much worse. You’re so fair, it doesn’t really matter.’ ”

“You didn’t say what race you are. I could imagine it has a bigger impact if you are anything other than White.”

Comment

Patients Looking for Cures—The general attitude within the forums was uplifting and encouraging, with users detailing how they respond to others in public and sharing their personal perspectives. We found a mix of information regarding disease management and treatment of vitiligo. Overall, there was uncertainty about treatments, with individuals expressing concern that their treatments were ineffective or had failed or that better alternatives would be more suitable for their condition. We found many anecdotal endorsements of homeopathic remedies for vitiligo, with users boasting that their disease had not only been cured but had never returned. Some users completely denounced these statements, while other threads seemed to revolve completely around “cure” discussions with no dissenting voices. The number of discussions related to homeopathy was concerning. Furthermore, there often were no moderators within threads to remove cure-related content, whether commercially endorsed or anecdotal. It is plausible that supplements and vitamins recommended by some physicians may be incorrectly interpreted as a “cure” in online discussions. Our findings are consistent with prior reports that forums are a platform to express dissatisfaction with treatment and the need for additional treatment options.^15,22

Concern Expressed by Health Care Providers—Prior qualitative research has described how patients with chronic dermatologic conditions believe that health care providers minimize patients’ psychological distress.^27,28 We found several accounts in which an individual had explicitly stated their provider had “belittled” the extent and impact of vitiligo when comparing skin phototypes. This suggests either that physicians underestimate the impact of vitiligo on their patients or that physicians are not expressing enough empathic concern about the impact the condition has on those affected.

Cosmetic Aspects of Vitiligo—Few clinical trials have investigated QOL and cosmetic acceptability of treatments as outcome measures.²⁹ We found several instances in which users with vitiligo had reported being dismissed as having a “cosmetic disease,” consistent with other work demonstrating the negative impact on such dismissals.²² Moreover, concealment and camouflage techniques frequently were discussed, demonstrating the relevance of cosmetic management as an important research topic.

Trustworthy Sources of Health Information—Patients still view physicians as trustworthy and a key source of health care information and advice.^30-32 Patients with vitiligo who have been directed to reliable information sources often express gratitude²² and want health professionals to remain an important source in their health information-seeking.³¹ Given the range in information discussed online, it may be valuable to invite patients to share what information they have encountered online.

Our study highlights the conflicting health information and advice shared by users in online forums, complicating an already psychologically burdensome condition. Guiding patients to credible, moderated sites and resources that are accurate, understandable, and easy to access may help dispel the conflicting messages and stories discussed in the online community.

Study Strengths and Limitations—Limitations included reporting bias and reliance on self-reported information on the diagnosis and extent of individuals’ vitiligo. Excluding social media websites and platforms from the data collection is a limitation to comprehensively assessing the topic of internet users with vitiligo. Many social media platforms direct patients and their family members to support groups and therefore may have excluded these particular individuals. Social media platforms were excluded from our research owing to the prerequisite of creating user accounts or registering as an online member. Our inclusion criteria were specific to forums that did not require registering or creating an account and were therefore freely accessible to all internet viewers. There is an inherent lack of context present in online forums, preventing data collection on individuals’ demographics and socioeconomic backgrounds. However, anonymity may have allowed individuals to express their thoughts more freely.

An integrated approach, along with our sampling method of online forums not requiring registration, allows for greater transferability and understanding of the health needs of the general public with vitiligo.

Conclusion

Individuals with vitiligo continue to seek peer psychosocial support for the physical and emotional management of their disease. Counseling those with vitiligo about cosmetic concealment options, homeopathy, and treatment scams remains paramount. Directing patients to evidence-based resources, along with providing structured sources of support, may help to improve the psychosocial burden and QOL experienced by patients with vitiligo. Connecting patients with local and national support groups moderated by physicians, such as the Global Vitiligo Foundation (https://globalvitiligofoundation.org/), may provide benefit to patients with vitiligo.

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A Seborrheic dermatitis in a woman with brown-gray greasy scale as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.

B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.

Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.

Epidemiology

Seborrheic dermatitis affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.¹

Key clinical features in darker skin tones

• In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petal–like) plaques may be present (Figure A). Also, hypopigmented patches and plaques may be prominent (Figures B and C). The classic description includes thin pink patches and plaques with white greasy scale on the face (Figure D).
• The scalp may have diffuse scale or isolated scaly plaques.

Worth noting

• In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
• Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.² In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
• If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
• It is appropriate to ask patients for their vehicle preference for medications.² For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
• Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
• Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
• Diffuse scale of tinea capitis in school-aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
• Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.^2,4

Health disparity highlight

Seborrheic dermatitis is among the most common cutaneous disorders diagnosed in patients with skin of color.^1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. Seborrheic dermatitis of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A Seborrheic dermatitis in a woman with brown-gray greasy scale as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.

B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.

Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.

Epidemiology

Seborrheic dermatitis affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.¹

Key clinical features in darker skin tones

• In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petal–like) plaques may be present (Figure A). Also, hypopigmented patches and plaques may be prominent (Figures B and C). The classic description includes thin pink patches and plaques with white greasy scale on the face (Figure D).
• The scalp may have diffuse scale or isolated scaly plaques.

Worth noting

• In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
• Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.² In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
• If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
• It is appropriate to ask patients for their vehicle preference for medications.² For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
• Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
• Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
• Diffuse scale of tinea capitis in school-aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
• Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.^2,4

Health disparity highlight

Seborrheic dermatitis is among the most common cutaneous disorders diagnosed in patients with skin of color.^1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. Seborrheic dermatitis of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A Seborrheic dermatitis in a woman with brown-gray greasy scale as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.

B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.

D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.

Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.

Epidemiology

Seborrheic dermatitis affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.¹

Key clinical features in darker skin tones

• In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petal–like) plaques may be present (Figure A). Also, hypopigmented patches and plaques may be prominent (Figures B and C). The classic description includes thin pink patches and plaques with white greasy scale on the face (Figure D).
• The scalp may have diffuse scale or isolated scaly plaques.

Worth noting

• In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
• Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.² In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
• If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
• It is appropriate to ask patients for their vehicle preference for medications.² For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
• Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
• Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
• Diffuse scale of tinea capitis in school-aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
• Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.^2,4

Health disparity highlight

Seborrheic dermatitis is among the most common cutaneous disorders diagnosed in patients with skin of color.^1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. Seborrheic dermatitis of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.

Cosmeceutical alternatives to hydroquinone, which is now restricted in the United States from inclusion in over-the-counter (OTC) products, are proliferating, along with new strategies to improve their efficacy, according to a report at the Skin of Color Update 2021.

“Ten or 15 years ago, I was showing a slide with five [alternatives to hydroquinone]. Now there are dozens,” reported Heather Woolery-Lloyd, MD, director of the skin of color division in the department of dermatology at the University of Miami.

The growth in alternatives to hydroquinone is timely. After threats to do so for more than a decade, the Food and Drug Administration finally banned hydroquinone from OTC products in 2020. The ban was folded into the Coronavirus Aid, Relief, and Economic Security (CARES) Act passed in March of 2020 and then implemented the following September.

Until the ban of hydroquinone, OTC products with this compound were widely sought by many individuals with darker skin tones to self-treat melasma and other forms of hyperpigmentation, according to Dr. Woolery-Lloyd. Hydroquinone is still available in prescription products, but she is often asked for OTC alternatives, and she says the list is long and getting longer.
 

Niacinamide

Detailing the products she has been recommending most frequently as substitutes, Dr. Woolery-Lloyd reported that several are supported by high quality studies. One example is niacinamide.

Of the several controlled studies she cited, one double-blind randomized trial found niacinamide to be equivalent to hydroquinone for melasma on the basis of colorimetric measures. The study compared 4% niacinamide cream applied on one side of the face with 4% hydroquinone cream applied on the other side in 27 patients with melasma. Although the proportion of responses rated good or excellent on a subjective basis was lower with niacinamide (44% vs. 55%), the difference was not statistically significant and niacinamide cream was clearly active, producing objective improvements in mast cell infiltrate and solar elastosis in melasma skin as well. Both were well tolerated.

In other studies, niacinamide has been shown to be effective in the treatment of melasma when combined with other active agents such as tranexamic acid, said Dr. Woolery-Lloyd, who added that OTC products containing niacinamide are now “among my favorites” when directing patients to cosmeceuticals for hyperpigmentation.
 

Topical vitamin C

Topical vitamin C or ascorbic acid is another. Like niacinamide, topical vitamin C has also been compared with hydroquinone in a double-blind, randomized trial. Although the niacinamide trial and this study were performed 10 or more years ago, these data have new relevance with the ban of OTC hydroquinone.

In the study, 5% ascorbic acid cream on one side of the face was compared with 4% hydroquinone cream, applied on the other side, in 16 women with melasma. Again, there were no statistical differences in colorimetric measures, but good to excellent results were reported for 93% of the sides of the face treated with hydroquinone versus 62.5% of the sides treated with vitamin C (P < .05). “Hydroquinone performed better, but the vitamin C was active and very well tolerated,” Dr. Woolery-Lloyd said.

However, the ascorbic acid cream was better tolerated, with a far lower rate of adverse events (6.2% vs. 68.7%), an advantage that makes it easy to recommend to patients, said Dr. Woolery-Lloyd, who now uses it frequently in her own practice.

Liquiritin, a licorice extract, is another lightening agent increasingly included in OTC products that she also recommends. In two older studies in medical journals published in Pakistan, both the 2% and 4% strengths of liquiritin cream outperformed hydroquinone on the basis of a Melasma Area and Severity Index (MASI) rating. The liquiritin cream was well tolerated in both studies.


 

Azelaic acid, tranexamic acid

OTC products containing azelaic acid are also effective for hyperpigmentation based on published trials in which they were compared with hydroquinone for treating melasma. In one study of 29 women with melasma cited by Dr. Woolery-Lloyd, 20% azelaic acid cream was more effective than hydroquinone 4% cream after 2 months of treatment on the basis of the mean MASI score (6.2 vs. 3.8).

The list also includes cysteamine, silymarin, and tranexamic acid.

In the case of tranexamic acid, Dr. Woolery-Lloyd cited a relatively recent study of 60 patients with melasma, comparing two strategies for applying tranexamic acid to treatment with hydroquinone over 12 weeks. Compared with 2% hydroquinone (applied nightly) or 1.8% liposomal tranexamic acid (applied twice a day), 5% tranexamic acid solution with microneedling (weekly) had a slightly greater rate of success defined as more than a 50% improvement in hyperpigmentation in an Asian population (30%, 27.8%, and 33.3%, respectively).

“Microneedling is a newer technology that appears to be effective at improving absorption,” said Dr. Woolery-Lloyd. She predicts that microneedling will be used with increasing frequency in combination with topical cosmeceuticals.

She also predicted that these topical agents will be increasingly employed in combinations as the field of cosmeceuticals becomes increasingly more sophisticated. “When it comes to skin quality, cosmeceuticals remain our first-line therapy, especially in skin of color,” she said.

The rapid growth and utility of OTC cosmeceuticals is an area that dermatologists need to be following, according to Darius Mehregan, MD, chair of the department of dermatology, Wayne State University, Detroit, who was senior author of an article published last year that reviewed the ingredients of popular OTC cosmeceuticals.

“Our patients have a great interest in cosmeceuticals and are looking to us for guidance. I think we have a responsibility to help them identify products supported by evidence and to warn them about potential side effects,” Dr. Mehregan, who was not at the meeting, said in an interview.

He agreed that the removal of hydroquinone from OTC products will create a specific need in the area of cosmeceuticals.

“Hydroquinone has for a long time been one of the most effective agents in OTC products for melasma, so patients are going to be looking for alternatives. Identifying which drugs have shown efficacy in controlled studies will be very helpful,” he said.

Dr. Woolery-Lloyd reports financial relationships with Ortho Dermatologics, L’Oréal, Galderma, Allergan, and Somabella Laboratories. Dr. Mehregan reports no potential conflicts of interest.

Cosmeceutical alternatives to hydroquinone, which is now restricted in the United States from inclusion in over-the-counter (OTC) products, are proliferating, along with new strategies to improve their efficacy, according to a report at the Skin of Color Update 2021.

“Ten or 15 years ago, I was showing a slide with five [alternatives to hydroquinone]. Now there are dozens,” reported Heather Woolery-Lloyd, MD, director of the skin of color division in the department of dermatology at the University of Miami.

The growth in alternatives to hydroquinone is timely. After threats to do so for more than a decade, the Food and Drug Administration finally banned hydroquinone from OTC products in 2020. The ban was folded into the Coronavirus Aid, Relief, and Economic Security (CARES) Act passed in March of 2020 and then implemented the following September.

Until the ban of hydroquinone, OTC products with this compound were widely sought by many individuals with darker skin tones to self-treat melasma and other forms of hyperpigmentation, according to Dr. Woolery-Lloyd. Hydroquinone is still available in prescription products, but she is often asked for OTC alternatives, and she says the list is long and getting longer.
 

Niacinamide

Detailing the products she has been recommending most frequently as substitutes, Dr. Woolery-Lloyd reported that several are supported by high quality studies. One example is niacinamide.

Of the several controlled studies she cited, one double-blind randomized trial found niacinamide to be equivalent to hydroquinone for melasma on the basis of colorimetric measures. The study compared 4% niacinamide cream applied on one side of the face with 4% hydroquinone cream applied on the other side in 27 patients with melasma. Although the proportion of responses rated good or excellent on a subjective basis was lower with niacinamide (44% vs. 55%), the difference was not statistically significant and niacinamide cream was clearly active, producing objective improvements in mast cell infiltrate and solar elastosis in melasma skin as well. Both were well tolerated.

In other studies, niacinamide has been shown to be effective in the treatment of melasma when combined with other active agents such as tranexamic acid, said Dr. Woolery-Lloyd, who added that OTC products containing niacinamide are now “among my favorites” when directing patients to cosmeceuticals for hyperpigmentation.
 

Topical vitamin C

Topical vitamin C or ascorbic acid is another. Like niacinamide, topical vitamin C has also been compared with hydroquinone in a double-blind, randomized trial. Although the niacinamide trial and this study were performed 10 or more years ago, these data have new relevance with the ban of OTC hydroquinone.

In the study, 5% ascorbic acid cream on one side of the face was compared with 4% hydroquinone cream, applied on the other side, in 16 women with melasma. Again, there were no statistical differences in colorimetric measures, but good to excellent results were reported for 93% of the sides of the face treated with hydroquinone versus 62.5% of the sides treated with vitamin C (P < .05). “Hydroquinone performed better, but the vitamin C was active and very well tolerated,” Dr. Woolery-Lloyd said.

However, the ascorbic acid cream was better tolerated, with a far lower rate of adverse events (6.2% vs. 68.7%), an advantage that makes it easy to recommend to patients, said Dr. Woolery-Lloyd, who now uses it frequently in her own practice.

Liquiritin, a licorice extract, is another lightening agent increasingly included in OTC products that she also recommends. In two older studies in medical journals published in Pakistan, both the 2% and 4% strengths of liquiritin cream outperformed hydroquinone on the basis of a Melasma Area and Severity Index (MASI) rating. The liquiritin cream was well tolerated in both studies.


 

Azelaic acid, tranexamic acid

OTC products containing azelaic acid are also effective for hyperpigmentation based on published trials in which they were compared with hydroquinone for treating melasma. In one study of 29 women with melasma cited by Dr. Woolery-Lloyd, 20% azelaic acid cream was more effective than hydroquinone 4% cream after 2 months of treatment on the basis of the mean MASI score (6.2 vs. 3.8).

The list also includes cysteamine, silymarin, and tranexamic acid.

In the case of tranexamic acid, Dr. Woolery-Lloyd cited a relatively recent study of 60 patients with melasma, comparing two strategies for applying tranexamic acid to treatment with hydroquinone over 12 weeks. Compared with 2% hydroquinone (applied nightly) or 1.8% liposomal tranexamic acid (applied twice a day), 5% tranexamic acid solution with microneedling (weekly) had a slightly greater rate of success defined as more than a 50% improvement in hyperpigmentation in an Asian population (30%, 27.8%, and 33.3%, respectively).

“Microneedling is a newer technology that appears to be effective at improving absorption,” said Dr. Woolery-Lloyd. She predicts that microneedling will be used with increasing frequency in combination with topical cosmeceuticals.

She also predicted that these topical agents will be increasingly employed in combinations as the field of cosmeceuticals becomes increasingly more sophisticated. “When it comes to skin quality, cosmeceuticals remain our first-line therapy, especially in skin of color,” she said.

The rapid growth and utility of OTC cosmeceuticals is an area that dermatologists need to be following, according to Darius Mehregan, MD, chair of the department of dermatology, Wayne State University, Detroit, who was senior author of an article published last year that reviewed the ingredients of popular OTC cosmeceuticals.

“Our patients have a great interest in cosmeceuticals and are looking to us for guidance. I think we have a responsibility to help them identify products supported by evidence and to warn them about potential side effects,” Dr. Mehregan, who was not at the meeting, said in an interview.

He agreed that the removal of hydroquinone from OTC products will create a specific need in the area of cosmeceuticals.

“Hydroquinone has for a long time been one of the most effective agents in OTC products for melasma, so patients are going to be looking for alternatives. Identifying which drugs have shown efficacy in controlled studies will be very helpful,” he said.

Dr. Woolery-Lloyd reports financial relationships with Ortho Dermatologics, L’Oréal, Galderma, Allergan, and Somabella Laboratories. Dr. Mehregan reports no potential conflicts of interest.

Cosmeceutical alternatives to hydroquinone, which is now restricted in the United States from inclusion in over-the-counter (OTC) products, are proliferating, along with new strategies to improve their efficacy, according to a report at the Skin of Color Update 2021.

“Ten or 15 years ago, I was showing a slide with five [alternatives to hydroquinone]. Now there are dozens,” reported Heather Woolery-Lloyd, MD, director of the skin of color division in the department of dermatology at the University of Miami.

The growth in alternatives to hydroquinone is timely. After threats to do so for more than a decade, the Food and Drug Administration finally banned hydroquinone from OTC products in 2020. The ban was folded into the Coronavirus Aid, Relief, and Economic Security (CARES) Act passed in March of 2020 and then implemented the following September.

Until the ban of hydroquinone, OTC products with this compound were widely sought by many individuals with darker skin tones to self-treat melasma and other forms of hyperpigmentation, according to Dr. Woolery-Lloyd. Hydroquinone is still available in prescription products, but she is often asked for OTC alternatives, and she says the list is long and getting longer.
 

Niacinamide

Detailing the products she has been recommending most frequently as substitutes, Dr. Woolery-Lloyd reported that several are supported by high quality studies. One example is niacinamide.

Of the several controlled studies she cited, one double-blind randomized trial found niacinamide to be equivalent to hydroquinone for melasma on the basis of colorimetric measures. The study compared 4% niacinamide cream applied on one side of the face with 4% hydroquinone cream applied on the other side in 27 patients with melasma. Although the proportion of responses rated good or excellent on a subjective basis was lower with niacinamide (44% vs. 55%), the difference was not statistically significant and niacinamide cream was clearly active, producing objective improvements in mast cell infiltrate and solar elastosis in melasma skin as well. Both were well tolerated.

In other studies, niacinamide has been shown to be effective in the treatment of melasma when combined with other active agents such as tranexamic acid, said Dr. Woolery-Lloyd, who added that OTC products containing niacinamide are now “among my favorites” when directing patients to cosmeceuticals for hyperpigmentation.
 

Topical vitamin C

Topical vitamin C or ascorbic acid is another. Like niacinamide, topical vitamin C has also been compared with hydroquinone in a double-blind, randomized trial. Although the niacinamide trial and this study were performed 10 or more years ago, these data have new relevance with the ban of OTC hydroquinone.

In the study, 5% ascorbic acid cream on one side of the face was compared with 4% hydroquinone cream, applied on the other side, in 16 women with melasma. Again, there were no statistical differences in colorimetric measures, but good to excellent results were reported for 93% of the sides of the face treated with hydroquinone versus 62.5% of the sides treated with vitamin C (P < .05). “Hydroquinone performed better, but the vitamin C was active and very well tolerated,” Dr. Woolery-Lloyd said.

However, the ascorbic acid cream was better tolerated, with a far lower rate of adverse events (6.2% vs. 68.7%), an advantage that makes it easy to recommend to patients, said Dr. Woolery-Lloyd, who now uses it frequently in her own practice.

Liquiritin, a licorice extract, is another lightening agent increasingly included in OTC products that she also recommends. In two older studies in medical journals published in Pakistan, both the 2% and 4% strengths of liquiritin cream outperformed hydroquinone on the basis of a Melasma Area and Severity Index (MASI) rating. The liquiritin cream was well tolerated in both studies.


 

Azelaic acid, tranexamic acid

OTC products containing azelaic acid are also effective for hyperpigmentation based on published trials in which they were compared with hydroquinone for treating melasma. In one study of 29 women with melasma cited by Dr. Woolery-Lloyd, 20% azelaic acid cream was more effective than hydroquinone 4% cream after 2 months of treatment on the basis of the mean MASI score (6.2 vs. 3.8).

The list also includes cysteamine, silymarin, and tranexamic acid.

In the case of tranexamic acid, Dr. Woolery-Lloyd cited a relatively recent study of 60 patients with melasma, comparing two strategies for applying tranexamic acid to treatment with hydroquinone over 12 weeks. Compared with 2% hydroquinone (applied nightly) or 1.8% liposomal tranexamic acid (applied twice a day), 5% tranexamic acid solution with microneedling (weekly) had a slightly greater rate of success defined as more than a 50% improvement in hyperpigmentation in an Asian population (30%, 27.8%, and 33.3%, respectively).

“Microneedling is a newer technology that appears to be effective at improving absorption,” said Dr. Woolery-Lloyd. She predicts that microneedling will be used with increasing frequency in combination with topical cosmeceuticals.

She also predicted that these topical agents will be increasingly employed in combinations as the field of cosmeceuticals becomes increasingly more sophisticated. “When it comes to skin quality, cosmeceuticals remain our first-line therapy, especially in skin of color,” she said.

The rapid growth and utility of OTC cosmeceuticals is an area that dermatologists need to be following, according to Darius Mehregan, MD, chair of the department of dermatology, Wayne State University, Detroit, who was senior author of an article published last year that reviewed the ingredients of popular OTC cosmeceuticals.

“Our patients have a great interest in cosmeceuticals and are looking to us for guidance. I think we have a responsibility to help them identify products supported by evidence and to warn them about potential side effects,” Dr. Mehregan, who was not at the meeting, said in an interview.

He agreed that the removal of hydroquinone from OTC products will create a specific need in the area of cosmeceuticals.

“Hydroquinone has for a long time been one of the most effective agents in OTC products for melasma, so patients are going to be looking for alternatives. Identifying which drugs have shown efficacy in controlled studies will be very helpful,” he said.

Dr. Woolery-Lloyd reports financial relationships with Ortho Dermatologics, L’Oréal, Galderma, Allergan, and Somabella Laboratories. Dr. Mehregan reports no potential conflicts of interest.

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

To the Editor:

A 40-year-old Somalian man presented to the dermatology clinic with lesions on the eyelids, tongue, lips, and hands of 8 years’ duration. He was a former refugee who had faced considerable stigma from his community due to his appearance. A review of systems was remarkable for decreased appetite but no weight loss. He reported no abdominal distention, early satiety, or urinary symptoms, and he had no personal history of diabetes mellitus or obesity. Physical examination demonstrated hyperpigmented velvety plaques in all skin folds and on the genitalia. Massive papillomatosis of the eyelid margins, tongue, and lips also was noted (Figure 1A). Flesh-colored papules also were scattered across the face. Punctate, flesh-colored papules were present on the volar and palmar hands (Figure 2A). Histopathology demonstrated pronounced papillomatous epidermal hyperplasia with negative human papillomavirus (HPV) type 16 and HPV-18 DNA studies. Given the appearance of malignant acanthosis nigricans with oral and conjunctival features, cutaneous papillomatosis, and tripe palms, concern for underlying malignancy was high. Malignancy workup, including upper and lower endoscopy as well as serial computed tomography scans of the chest, abdomen, and pelvis, was unrevealing.

Laboratory investigation revealed a positive Schistosoma IgG antibody (0.38 geometric mean egg count) and peripheral eosinophilia (1.09 ×10³/μL), which normalized after praziquantel therapy. With no malignancy identified over the preceding 6-month period, treatment with acitretin 50 mg daily was initiated based on limited literature support.^1-3 Treatment led to reduction in the size and number of papillomas (Figure 1B) and tripe palms (Figure 2B) with increased mobility of hands, lips, and tongue. The patient underwent oculoplastic surgery to reduce the papilloma burden along the eyelid margins. Subsequent cystoscopy 9 months after the initial presentation revealed low-grade transitional cell carcinoma of the bladder. Intraoperative mitomycin C led to tumor shrinkage and, with continued treatment with daily acitretin, dramatic improvement of all cutaneous and mucosal symptoms (Figure 1C and Figure 2C). To date, his cutaneous symptoms have resolved.

This case demonstrated a unique presentation of multiple paraneoplastic signs in bladder transitional cell carcinoma. The presence of malignant acanthosis nigricans (including oral and conjunctival involvement), cutaneous papillomatosis, and tripe palms have been individually documented in various types of gastric malignancies.⁴ Acanthosis nigricans often is secondary to diabetes and obesity, presenting with diffuse, thickened, velvety plaques in the flexural areas. Malignant acanthosis nigricans is a rare, rapidly progressive condition that often presents over a period of weeks to months; it almost always is associated with internal malignancies. It often has more extensive involvement, extending beyond the flexural areas, than typical acanthosis nigricans.⁴ Oral involvement can be either hypertrophic or papillomatous; papillomatosis of the oral mucosa was reported in over 40% of malignant acanthosis nigricans cases (N=200).⁵ Cases with conjunctival involvement are less common.⁶ Although malignant acanthosis nigricans often is codiagnosed with a malignancy, it can precede the cancer diagnosis in some cases.^7,8 A majority of cases are associated with adenocarcinomas of the gastrointestinal tract.⁴ Progressive mucocutaneous papillomatosis also is a rare paraneoplastic condition that most commonly is associated with gastric adenocarcinomas. Progressive mucocutaneous papillomatosis often presents rapidly as verrucous growths on cutaneous surfaces (including the hands and face) but also can affect mucosal surfaces such as the mouth and conjunctiva.^9-11 Tripe palms are characterized by exaggerated dermatoglyphics with diffuse palmar ridging and hyperkeratosis. Tripe palms most often are associated with pulmonary malignancies. When tripe palms are present with malignant acanthosis nigricans, they reflect up to a one-third incidence of gastrointestinal malignancy.^12,13

Despite the individual presentation of these paraneoplastic signs in a variety of malignancies, synchronous presentation is rare. A brief literature review only identified 6 cases of concurrent acanthosis nigricans, tripe palms, and progressive mucocutaneous papillomatosis with an underlying gastrointestinal malignancy.^1,11,14-17 Two additional reports described tripe palms with oral acanthosis nigricans and progressive mucocutaneous papillomatosis in metastatic gastric adenocarcinoma and renal urothelial carcinoma.^2,18 An additional case of all 3 paraneoplastic conditions was reported in the setting of metastatic cervical cancer (HPV positive).¹⁹ Per a recent case report and literature review,²⁰ there have only been 8 cases of acanthosis nigricans reported in bladder transitional cell carcinoma,^20-27 half of which have included oral malignant acanthosis nigricans.^20-23 Only one report of concurrent cutaneous and oral malignant acanthosis nigricans and triple palms in the setting of bladder cancer has been reported.²⁰ Given the extensive conjunctival involvement and cutaneous papillomatosis in our patient, ours is a rarely reported case of concurrent malignant mucocutaneous acanthosis nigricans, tripe palms, and progressive papillomatosis in transitional cell bladder carcinoma. We believe it is imperative to consider the role of this malignancy as a cause of these paraneoplastic conditions.

Although these paraneoplastic conditions rarely co-occur, our case further offers a common molecular pathway for these conditions.²⁸ In these paraneoplastic conditions, the stimulating factor is thought to be tumor growth factor α, which is structurally related to epidermal growth factor (EGF). Epidermal growth factor receptors (EGFRs) are found in the basal layer of the epidermis, where activation stimulates keratinocyte growth and leads to the cutaneous manifestation of symptoms.²⁸ Fibroblast growth factor receptor 3 mutations are found in most noninvasive transitional cell tumors of the bladder.²⁹ The fibroblast growth factor pathway is distinctly different from the tumor growth factor α and EGF pathways.³⁰ However, this association with transitional cell carcinoma suggests that fibroblast growth factor receptor 3 also may be implicated in these paraneoplastic conditions.

Our patient responded well to treatment with acitretin 50 mg daily. The mechanism of action of retinoids involves inducing mitotic activity and desmosomal shedding.³¹ Retinoids downregulate EGFR expression and activation in EGF-stimulated cells.³² We hypothesize that these oral retinoids decreased the growth stimulus and thereby improved cutaneous signs in the setting of our patient’s transitional cell cancer. Although definitive therapy is malignancy management, our case highlights the utility of adjunctive measures such as oral retinoids and surgical debulking. While previous cases have reported use of retinoids at a lower dosage than used in this case, oral lesions often have only been mildly improved with little impact on other cutaneous symptoms.^1,2 In one case of malignant acanthosis nigricans and oral papillomatosis, isotretinoin 25 mg once every 2 to 3 days led to a moderate decrease in hyperkeratosis and papillomas, but the patient was lost to follow-up.³ Our case highlights the use of higher daily doses of oral retinoids for over 9 months, resulting in marked improvement in both the mucosal and cutaneous symptoms of acanthosis nigricans, progressive mucocutaneous papillomatosis, and tripe palms. Therefore, oral acitretin should be considered as adjuvant therapy for these paraneoplastic conditions.

By reporting this case, we hope to demonstrate the importance of considering other forms of malignancies in the presence of paraneoplastic conditions. Although gastric malignancies more commonly are associated with these conditions, bladder carcinomas also can present with cutaneous manifestations. The presence of these paraneoplastic conditions alone or together rarely is reported in urologic cancers and generally is considered to be an indicator of poor prognosis. Paraneoplastic conditions often develop rapidly and occur in very advanced malignancies.⁴ The disfiguring presentation in our case also had unusual diagnostic challenges. The presence of these conditions for 8 years and nonmetastatic advanced malignancy suggest a more indolent process and that these signs are not always an indicator of poor prognosis. Future patients with these paraneoplastic conditions may benefit from both a thorough malignancy screen, including cystoscopy, and high daily doses of oral retinoids.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.