Pigmentation Disorders

The Diagnosis: Lichen Planus Pemphigoides

A skin biopsy from the right thigh demonstrated subepidermal blisters containing neutrophils (Figure 1). Direct immunofluorescence revealed linear basement membrane zone staining with C3 and trace staining with IgG (Figure 2), supporting a diagnosis of lichen planus pemphigoides (LPP). Oral prednisone—starting at 60 mg daily and tapered to 40 mg for a week, 20 mg for a week, then 10 mg for a month—along with triamcinolone ointment 0.1% to affected areas led to improvement. Hydrochlorothiazide and UV light therapy were discontinued. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily prescribed as adjunctive therapy also led to improvement. The patient achieved remission with doxycycline and was doing well without prednisone; however, he experienced a flare of his disease about 6 months later and was started on mycophenolate mofetil 1 g twice daily after clearance from his gastroenterologist, given his history of hepatitis B. He has been doing well since starting mycophenolate mofetil.

Lichen planus pemphigoides is a rare autoimmune bullous dermatosis with features of both lichen planus and bullous pemphigoid.¹ Violaceous papules and tense bullae may be superimposed or arise independently. The chest, abdomen, back, and upper and lower extremities typically are involved.² Oral mucosal involvement with white reticular streaks or erosions and nail involvement have been reported.² Histopathologic and immunologic findings establish the diagnosis. Lichen planus pemphigoides is associated with subepidermal bullae and linear deposits of IgG and C3 on the basement membrane zone.¹ Autoantibodies to bullous pemphigoid (BP) antigens BP180 and BP230 are associated with LPP.³ The pathogenesis of LPP remains unclear, but there are associations with chronic diseases, medications, and certain therapies.^1,4-6 Several case reports have linked LPP to chronic viral hepatitis infections, as well as malignant tumors of the skin, mucosa, and gastrointestinal tract.² Lichen planus pemphigoides has been reported in a patient on entecavir for hepatitis B as well as in a patient treated for hepatitis C with interferon and ribavirin.¹ Lichen planus pemphigoides has been described in patients treated with the angiotensin-converting enzyme inhibitors enalapril, captopril, and ramipril.^4,5,7 UV phototherapy also has been associated with the development of LPP.⁶ Hydrochlorothiazide previously has been reported as a cause of drug-induced lichen planus.⁸ A PubMed search of articles indexed for MEDLINE using the terms lichen planus pemphigoides and hydrochlorothiazide revealed no reports of hydrochlorothiazide-induced LPP.

Lichen planus pemphigoides demonstrates overlap with other blistering dermatoses, such as BP, bullous lupus erythematosus, and bullous lichen planus. Although histologically and immunologically similar to BP, LPP can be differentiated clinically by the presence of violaceous papules or plaques typical of lichen planus.⁹ Bullous pemphigoid is more common in individuals older than 70 years, whereas LPP tends to occur in middle-aged adults.² Bullous lupus erythematosus usually is associated with manifestations of systemic lupus erythematosus and autoantibodies to collagen type VII.¹⁰ Salt-split skin studies demonstrate immunofluorescence on the dermal side of the split. Individuals affected by bullous lupus erythematosus typically have a history of photosensitivity.¹⁰ Blisters in LPP may form de novo from unaffected skin, whereas the bullae in bullous lichen planus are limited to existing lichenoid papules.⁹ The autoantibodies typical of LPP are absent in bullous lichen planus. Lichen planus actinicus is a variant of lichen planus that presents with annular, dyschromic, or violaceous plaques in a photodistributed pattern without bullous lesions.⁹

Lichen planus pemphigoides most commonly is treated with systemic corticosteroids. Topical steroids, dapsone, erythromycin, tetracycline and nicotinamide, azathioprine, and mycophenolate mofetil have been reported as adjuncts to systemic steroid therapy.^2,11 Most reports describe treatment success with resolution of blistering lesions.

The Diagnosis: Lichen Planus Pemphigoides

A skin biopsy from the right thigh demonstrated subepidermal blisters containing neutrophils (Figure 1). Direct immunofluorescence revealed linear basement membrane zone staining with C3 and trace staining with IgG (Figure 2), supporting a diagnosis of lichen planus pemphigoides (LPP). Oral prednisone—starting at 60 mg daily and tapered to 40 mg for a week, 20 mg for a week, then 10 mg for a month—along with triamcinolone ointment 0.1% to affected areas led to improvement. Hydrochlorothiazide and UV light therapy were discontinued. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily prescribed as adjunctive therapy also led to improvement. The patient achieved remission with doxycycline and was doing well without prednisone; however, he experienced a flare of his disease about 6 months later and was started on mycophenolate mofetil 1 g twice daily after clearance from his gastroenterologist, given his history of hepatitis B. He has been doing well since starting mycophenolate mofetil.

Lichen planus pemphigoides is a rare autoimmune bullous dermatosis with features of both lichen planus and bullous pemphigoid.¹ Violaceous papules and tense bullae may be superimposed or arise independently. The chest, abdomen, back, and upper and lower extremities typically are involved.² Oral mucosal involvement with white reticular streaks or erosions and nail involvement have been reported.² Histopathologic and immunologic findings establish the diagnosis. Lichen planus pemphigoides is associated with subepidermal bullae and linear deposits of IgG and C3 on the basement membrane zone.¹ Autoantibodies to bullous pemphigoid (BP) antigens BP180 and BP230 are associated with LPP.³ The pathogenesis of LPP remains unclear, but there are associations with chronic diseases, medications, and certain therapies.^1,4-6 Several case reports have linked LPP to chronic viral hepatitis infections, as well as malignant tumors of the skin, mucosa, and gastrointestinal tract.² Lichen planus pemphigoides has been reported in a patient on entecavir for hepatitis B as well as in a patient treated for hepatitis C with interferon and ribavirin.¹ Lichen planus pemphigoides has been described in patients treated with the angiotensin-converting enzyme inhibitors enalapril, captopril, and ramipril.^4,5,7 UV phototherapy also has been associated with the development of LPP.⁶ Hydrochlorothiazide previously has been reported as a cause of drug-induced lichen planus.⁸ A PubMed search of articles indexed for MEDLINE using the terms lichen planus pemphigoides and hydrochlorothiazide revealed no reports of hydrochlorothiazide-induced LPP.

Lichen planus pemphigoides demonstrates overlap with other blistering dermatoses, such as BP, bullous lupus erythematosus, and bullous lichen planus. Although histologically and immunologically similar to BP, LPP can be differentiated clinically by the presence of violaceous papules or plaques typical of lichen planus.⁹ Bullous pemphigoid is more common in individuals older than 70 years, whereas LPP tends to occur in middle-aged adults.² Bullous lupus erythematosus usually is associated with manifestations of systemic lupus erythematosus and autoantibodies to collagen type VII.¹⁰ Salt-split skin studies demonstrate immunofluorescence on the dermal side of the split. Individuals affected by bullous lupus erythematosus typically have a history of photosensitivity.¹⁰ Blisters in LPP may form de novo from unaffected skin, whereas the bullae in bullous lichen planus are limited to existing lichenoid papules.⁹ The autoantibodies typical of LPP are absent in bullous lichen planus. Lichen planus actinicus is a variant of lichen planus that presents with annular, dyschromic, or violaceous plaques in a photodistributed pattern without bullous lesions.⁹

Lichen planus pemphigoides most commonly is treated with systemic corticosteroids. Topical steroids, dapsone, erythromycin, tetracycline and nicotinamide, azathioprine, and mycophenolate mofetil have been reported as adjuncts to systemic steroid therapy.^2,11 Most reports describe treatment success with resolution of blistering lesions.

The Diagnosis: Lichen Planus Pemphigoides

A skin biopsy from the right thigh demonstrated subepidermal blisters containing neutrophils (Figure 1). Direct immunofluorescence revealed linear basement membrane zone staining with C3 and trace staining with IgG (Figure 2), supporting a diagnosis of lichen planus pemphigoides (LPP). Oral prednisone—starting at 60 mg daily and tapered to 40 mg for a week, 20 mg for a week, then 10 mg for a month—along with triamcinolone ointment 0.1% to affected areas led to improvement. Hydrochlorothiazide and UV light therapy were discontinued. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily prescribed as adjunctive therapy also led to improvement. The patient achieved remission with doxycycline and was doing well without prednisone; however, he experienced a flare of his disease about 6 months later and was started on mycophenolate mofetil 1 g twice daily after clearance from his gastroenterologist, given his history of hepatitis B. He has been doing well since starting mycophenolate mofetil.

Lichen planus pemphigoides is a rare autoimmune bullous dermatosis with features of both lichen planus and bullous pemphigoid.¹ Violaceous papules and tense bullae may be superimposed or arise independently. The chest, abdomen, back, and upper and lower extremities typically are involved.² Oral mucosal involvement with white reticular streaks or erosions and nail involvement have been reported.² Histopathologic and immunologic findings establish the diagnosis. Lichen planus pemphigoides is associated with subepidermal bullae and linear deposits of IgG and C3 on the basement membrane zone.¹ Autoantibodies to bullous pemphigoid (BP) antigens BP180 and BP230 are associated with LPP.³ The pathogenesis of LPP remains unclear, but there are associations with chronic diseases, medications, and certain therapies.^1,4-6 Several case reports have linked LPP to chronic viral hepatitis infections, as well as malignant tumors of the skin, mucosa, and gastrointestinal tract.² Lichen planus pemphigoides has been reported in a patient on entecavir for hepatitis B as well as in a patient treated for hepatitis C with interferon and ribavirin.¹ Lichen planus pemphigoides has been described in patients treated with the angiotensin-converting enzyme inhibitors enalapril, captopril, and ramipril.^4,5,7 UV phototherapy also has been associated with the development of LPP.⁶ Hydrochlorothiazide previously has been reported as a cause of drug-induced lichen planus.⁸ A PubMed search of articles indexed for MEDLINE using the terms lichen planus pemphigoides and hydrochlorothiazide revealed no reports of hydrochlorothiazide-induced LPP.

Lichen planus pemphigoides demonstrates overlap with other blistering dermatoses, such as BP, bullous lupus erythematosus, and bullous lichen planus. Although histologically and immunologically similar to BP, LPP can be differentiated clinically by the presence of violaceous papules or plaques typical of lichen planus.⁹ Bullous pemphigoid is more common in individuals older than 70 years, whereas LPP tends to occur in middle-aged adults.² Bullous lupus erythematosus usually is associated with manifestations of systemic lupus erythematosus and autoantibodies to collagen type VII.¹⁰ Salt-split skin studies demonstrate immunofluorescence on the dermal side of the split. Individuals affected by bullous lupus erythematosus typically have a history of photosensitivity.¹⁰ Blisters in LPP may form de novo from unaffected skin, whereas the bullae in bullous lichen planus are limited to existing lichenoid papules.⁹ The autoantibodies typical of LPP are absent in bullous lichen planus. Lichen planus actinicus is a variant of lichen planus that presents with annular, dyschromic, or violaceous plaques in a photodistributed pattern without bullous lesions.⁹

Lichen planus pemphigoides most commonly is treated with systemic corticosteroids. Topical steroids, dapsone, erythromycin, tetracycline and nicotinamide, azathioprine, and mycophenolate mofetil have been reported as adjuncts to systemic steroid therapy.^2,11 Most reports describe treatment success with resolution of blistering lesions.

The Diagnosis: Addison Disease in the Context of Polyglandular Autoimmune Syndrome Type 2

The patient’s hormone levels as well as distinct clinical features led to a diagnosis of Addison disease in the context of polyglandular autoimmune syndrome type 2 (PAS-2). Approximately 50% of PAS-2 cases are familiar, and different modes of inheritance—autosomal recessive, autosomal dominant, and polygenic—have been reported. Women are affected up to 3 times more often than men.^1,2 The age of onset ranges from infancy to late adulthood, with most cases occurring in early adulthood. Primary adrenal insufficiency (Addison disease) is  the principal manifestation of PAS-2. It appears in approximately 50% of patients, occurring simultaneously with autoimmune thyroid disease or diabetes mellitus in 20% of patients and following them in 30% of patients.^1,2 Autoimmune thyroid diseases such as chronic autoimmune thyroiditis and occasionally Graves disease as well as type 1 diabetes mellitus also are common. Polyglandular autoimmune syndrome type 2 with primary adrenal insufficiency and autoimmune thyroid disease was formerly referred to as Schmidt syndrome.³ It must be differentiated from polyglandular autoimmune syndrome type 1, a rare condition that also is referred to as autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy syndrome.^1,3 As with any other cause of adrenal insufficiency, the treatment involves hormone replacement therapy up to normal levels and then tapering according to stress levels (ie, surgery or infections that require a dose increase). Our patient was diagnosed according to hormone levels and clinical features and was started on 30 mg daily of hydrocortisone and 50 μg daily of levothyroxine. No improvement in her condition was noted after 6 months of treatment. The patient is still under yearly follow-up, and the mucous hyperpigmentation faded approximately 6 months after hormonal homeostasis was achieved.

Peutz-Jeghers syndrome is inherited in an autosomal-dominant fashion. It is characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk for gastrointestinal and nongastrointestinal cancer. Mucocutaneous pigmented macules most commonly occur on the lips and perioral region, buccal mucosa, and the palms and soles. However, mucocutaneous pigmentation usually occurs during the first 1 to 2 years of life, increases in size and number over the ensuing years, and usually fades after puberty.⁴

Laugier-Hunziker syndrome is an acquired benign disorder presenting in adults with lentigines on the lips and buccal mucosa. It frequently is accompaniedby longitudinal melanonychia, macular pigmentation of the genitals, and involvement of the palms and soles. The diagnosis of Laugier-Hunziker syndrome is one of exclusion and is made after ruling out other causes of oral and labial hyperpigmentation, including physiologic pigmentation seen in darker-skinned individuals as well as inherited diseases associated with lentiginosis, requiring complete physical examination, endoscopy, and colonscopy.⁵

A wide variety of drugs and chemicals can lead to diffuse cutaneous hyperpigmentation. Increased production of melanin and/or the deposition of drug complexes or metals in the dermis is responsible for the skin discoloration. Drugs that most often cause hyperpigmentation on mucosal surfaces are hydroxychloroquine, minocycline, nicotine, silver, and some chemotherapy agents. The hyperpigmentation usually resolves with discontinuation of the offending agent, but the course may be prolonged over months to years.⁶

Changes in the skin and subcutaneous tissue occur in patients with Cushing syndrome. Hyperpigmentation is induced by increased secretion of adrenocorticotropic hormone, not cortisol, and occurs most often in patients with the ectopic adrenocorticotropic hormone syndrome. Hyperpigmentation may be generalized but is more intense in areas exposed to light (eg, face, neck, dorsal aspects of the hands) or to chronic mild trauma, friction, or pressure (eg, elbows, knees, spine, knuckles). Patchy pigmentation may occur on the inner surface of the lips and the buccal mucosa along the line of dental occlusion. Acanthosis nigricans also can be present in the axillae and around the neck.⁷

The Diagnosis: Addison Disease in the Context of Polyglandular Autoimmune Syndrome Type 2

The patient’s hormone levels as well as distinct clinical features led to a diagnosis of Addison disease in the context of polyglandular autoimmune syndrome type 2 (PAS-2). Approximately 50% of PAS-2 cases are familiar, and different modes of inheritance—autosomal recessive, autosomal dominant, and polygenic—have been reported. Women are affected up to 3 times more often than men.^1,2 The age of onset ranges from infancy to late adulthood, with most cases occurring in early adulthood. Primary adrenal insufficiency (Addison disease) is  the principal manifestation of PAS-2. It appears in approximately 50% of patients, occurring simultaneously with autoimmune thyroid disease or diabetes mellitus in 20% of patients and following them in 30% of patients.^1,2 Autoimmune thyroid diseases such as chronic autoimmune thyroiditis and occasionally Graves disease as well as type 1 diabetes mellitus also are common. Polyglandular autoimmune syndrome type 2 with primary adrenal insufficiency and autoimmune thyroid disease was formerly referred to as Schmidt syndrome.³ It must be differentiated from polyglandular autoimmune syndrome type 1, a rare condition that also is referred to as autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy syndrome.^1,3 As with any other cause of adrenal insufficiency, the treatment involves hormone replacement therapy up to normal levels and then tapering according to stress levels (ie, surgery or infections that require a dose increase). Our patient was diagnosed according to hormone levels and clinical features and was started on 30 mg daily of hydrocortisone and 50 μg daily of levothyroxine. No improvement in her condition was noted after 6 months of treatment. The patient is still under yearly follow-up, and the mucous hyperpigmentation faded approximately 6 months after hormonal homeostasis was achieved.

Peutz-Jeghers syndrome is inherited in an autosomal-dominant fashion. It is characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk for gastrointestinal and nongastrointestinal cancer. Mucocutaneous pigmented macules most commonly occur on the lips and perioral region, buccal mucosa, and the palms and soles. However, mucocutaneous pigmentation usually occurs during the first 1 to 2 years of life, increases in size and number over the ensuing years, and usually fades after puberty.⁴

Laugier-Hunziker syndrome is an acquired benign disorder presenting in adults with lentigines on the lips and buccal mucosa. It frequently is accompaniedby longitudinal melanonychia, macular pigmentation of the genitals, and involvement of the palms and soles. The diagnosis of Laugier-Hunziker syndrome is one of exclusion and is made after ruling out other causes of oral and labial hyperpigmentation, including physiologic pigmentation seen in darker-skinned individuals as well as inherited diseases associated with lentiginosis, requiring complete physical examination, endoscopy, and colonscopy.⁵

A wide variety of drugs and chemicals can lead to diffuse cutaneous hyperpigmentation. Increased production of melanin and/or the deposition of drug complexes or metals in the dermis is responsible for the skin discoloration. Drugs that most often cause hyperpigmentation on mucosal surfaces are hydroxychloroquine, minocycline, nicotine, silver, and some chemotherapy agents. The hyperpigmentation usually resolves with discontinuation of the offending agent, but the course may be prolonged over months to years.⁶

Changes in the skin and subcutaneous tissue occur in patients with Cushing syndrome. Hyperpigmentation is induced by increased secretion of adrenocorticotropic hormone, not cortisol, and occurs most often in patients with the ectopic adrenocorticotropic hormone syndrome. Hyperpigmentation may be generalized but is more intense in areas exposed to light (eg, face, neck, dorsal aspects of the hands) or to chronic mild trauma, friction, or pressure (eg, elbows, knees, spine, knuckles). Patchy pigmentation may occur on the inner surface of the lips and the buccal mucosa along the line of dental occlusion. Acanthosis nigricans also can be present in the axillae and around the neck.⁷

The Diagnosis: Addison Disease in the Context of Polyglandular Autoimmune Syndrome Type 2

The patient’s hormone levels as well as distinct clinical features led to a diagnosis of Addison disease in the context of polyglandular autoimmune syndrome type 2 (PAS-2). Approximately 50% of PAS-2 cases are familiar, and different modes of inheritance—autosomal recessive, autosomal dominant, and polygenic—have been reported. Women are affected up to 3 times more often than men.^1,2 The age of onset ranges from infancy to late adulthood, with most cases occurring in early adulthood. Primary adrenal insufficiency (Addison disease) is  the principal manifestation of PAS-2. It appears in approximately 50% of patients, occurring simultaneously with autoimmune thyroid disease or diabetes mellitus in 20% of patients and following them in 30% of patients.^1,2 Autoimmune thyroid diseases such as chronic autoimmune thyroiditis and occasionally Graves disease as well as type 1 diabetes mellitus also are common. Polyglandular autoimmune syndrome type 2 with primary adrenal insufficiency and autoimmune thyroid disease was formerly referred to as Schmidt syndrome.³ It must be differentiated from polyglandular autoimmune syndrome type 1, a rare condition that also is referred to as autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy syndrome.^1,3 As with any other cause of adrenal insufficiency, the treatment involves hormone replacement therapy up to normal levels and then tapering according to stress levels (ie, surgery or infections that require a dose increase). Our patient was diagnosed according to hormone levels and clinical features and was started on 30 mg daily of hydrocortisone and 50 μg daily of levothyroxine. No improvement in her condition was noted after 6 months of treatment. The patient is still under yearly follow-up, and the mucous hyperpigmentation faded approximately 6 months after hormonal homeostasis was achieved.

Peutz-Jeghers syndrome is inherited in an autosomal-dominant fashion. It is characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk for gastrointestinal and nongastrointestinal cancer. Mucocutaneous pigmented macules most commonly occur on the lips and perioral region, buccal mucosa, and the palms and soles. However, mucocutaneous pigmentation usually occurs during the first 1 to 2 years of life, increases in size and number over the ensuing years, and usually fades after puberty.⁴

Laugier-Hunziker syndrome is an acquired benign disorder presenting in adults with lentigines on the lips and buccal mucosa. It frequently is accompaniedby longitudinal melanonychia, macular pigmentation of the genitals, and involvement of the palms and soles. The diagnosis of Laugier-Hunziker syndrome is one of exclusion and is made after ruling out other causes of oral and labial hyperpigmentation, including physiologic pigmentation seen in darker-skinned individuals as well as inherited diseases associated with lentiginosis, requiring complete physical examination, endoscopy, and colonscopy.⁵

A wide variety of drugs and chemicals can lead to diffuse cutaneous hyperpigmentation. Increased production of melanin and/or the deposition of drug complexes or metals in the dermis is responsible for the skin discoloration. Drugs that most often cause hyperpigmentation on mucosal surfaces are hydroxychloroquine, minocycline, nicotine, silver, and some chemotherapy agents. The hyperpigmentation usually resolves with discontinuation of the offending agent, but the course may be prolonged over months to years.⁶

Changes in the skin and subcutaneous tissue occur in patients with Cushing syndrome. Hyperpigmentation is induced by increased secretion of adrenocorticotropic hormone, not cortisol, and occurs most often in patients with the ectopic adrenocorticotropic hormone syndrome. Hyperpigmentation may be generalized but is more intense in areas exposed to light (eg, face, neck, dorsal aspects of the hands) or to chronic mild trauma, friction, or pressure (eg, elbows, knees, spine, knuckles). Patchy pigmentation may occur on the inner surface of the lips and the buccal mucosa along the line of dental occlusion. Acanthosis nigricans also can be present in the axillae and around the neck.⁷

To the Editor:

A 46-year-old overweight woman presented with a rash in the axillae of 2 months’ duration. She did not report any additional symptoms such as pruritus or pain. She reported changing her deodorant recently from Secret Original to Secret Clinical Strength (both Procter & Gamble). Her medical history was remarkable for asthma and gastroesophageal reflux disease. Clinical examination revealed erythematous-brown, stuccolike, hyperkeratotic papules coalescing into plaques in recently shaved axillae, affecting the left axilla more than the right axilla (Figure 1). The clinical differential diagnosis included granular parakeratosis, intertrigo, Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, acanthosis nigricans, seborrheic keratoses, and irritant or allergic contact dermatitis. A punch biopsy revealed a marked compact parakeratotic horn with retention of keratohyalin granules (Figure 2). The subjacent epidermis showed some acanthosis and spongiosis with mild chronic inflammation of the dermal rim. Based on histopathology, granular parakeratosis was diagnosed.

At a subsequent visit 2 weeks later, we prescribed glycolic acid lotion 10% applied to the axillae twice daily, plus tretinoin gel 0.05% applied to the axillae each evening. She reported clearing after 1 week of therapy. She also had changed her deodorant from Secret Clinical Strength back to the usual Secret Original. The patient discontinued topical treatment after clearing of the lesions. Three weeks later, clinical examination revealed postinflammatory hyperpigmentation in the axillae, and the prior lesions had resolved (Figure 3).

The cause is unknown but possibly related to irritation from rubbing, occlusion, sweating, or deodorants.^5,7 Cases indicate a link to obesity. Hypotheses as to the etiology include the disruption of cornification. Normally, filaggrin maintains the keratohyaline granules in the stratum corneum during cornification. Therefore, the retention of keratohyaline granules in granular parakeratosis may be due to a defect in processing profilaggrin to filaggrin, which has been proposed based on ultrastructural and immunohistochemical studies.⁸

The differential diagnosis includes granular parakeratosis, intertrigo (caused by seborrheic dermatitis, candidiasis, inverse psoriasis, or erythrasma), Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, and irritant or allergic contact dermatitis. The papules may resemble seborrheic keratoses, while the plaques can be mistaken for acanthosis nigricans.

Therapeutic success has been reported with topical corticosteroids, vitamin D analogues, topical or oral retinoids, ammonium lactate, calcineurin inhibitors, topical or oral antifungals, cryotherapy, and botulinum toxin injections.^3,9-11 In addition, parakeratosis has decreased in biopsies from psoriatic patients after acitretin, methotrexate, and phototherapy, which may be alternative treatments for unusually difficult or recalcitrant cases of granular parakeratosis. To minimize side effects and resolve the papules quickly, we combined 2 synergistic agents—glycolic acid and tretinoin—each with different mechanisms of action, and we observed excellent clinical response.

Granular parakeratosis is possibly related to a combination of topical products that potentiate irritation, rubbing, and occlusion of sweat. Multiple treatment modalities likely contribute to clearing, the most important being removal of any triggering topical products. Our patient’s change in deodorant may have been the inciting factor for the disease. Withdrawal of the Secret Clinical Strength deodorant prompted clearing, though topical retinoid and glycolic acid acted as facilitating therapies for timely results. A thorough history, as highlighted by this case, may help pinpoint etiologic factors. By identifying a seemingly innocuous change in hygienic routine, we were able to minimize the need for ongoing therapy.

To the Editor:

A 46-year-old overweight woman presented with a rash in the axillae of 2 months’ duration. She did not report any additional symptoms such as pruritus or pain. She reported changing her deodorant recently from Secret Original to Secret Clinical Strength (both Procter & Gamble). Her medical history was remarkable for asthma and gastroesophageal reflux disease. Clinical examination revealed erythematous-brown, stuccolike, hyperkeratotic papules coalescing into plaques in recently shaved axillae, affecting the left axilla more than the right axilla (Figure 1). The clinical differential diagnosis included granular parakeratosis, intertrigo, Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, acanthosis nigricans, seborrheic keratoses, and irritant or allergic contact dermatitis. A punch biopsy revealed a marked compact parakeratotic horn with retention of keratohyalin granules (Figure 2). The subjacent epidermis showed some acanthosis and spongiosis with mild chronic inflammation of the dermal rim. Based on histopathology, granular parakeratosis was diagnosed.

At a subsequent visit 2 weeks later, we prescribed glycolic acid lotion 10% applied to the axillae twice daily, plus tretinoin gel 0.05% applied to the axillae each evening. She reported clearing after 1 week of therapy. She also had changed her deodorant from Secret Clinical Strength back to the usual Secret Original. The patient discontinued topical treatment after clearing of the lesions. Three weeks later, clinical examination revealed postinflammatory hyperpigmentation in the axillae, and the prior lesions had resolved (Figure 3).

The cause is unknown but possibly related to irritation from rubbing, occlusion, sweating, or deodorants.^5,7 Cases indicate a link to obesity. Hypotheses as to the etiology include the disruption of cornification. Normally, filaggrin maintains the keratohyaline granules in the stratum corneum during cornification. Therefore, the retention of keratohyaline granules in granular parakeratosis may be due to a defect in processing profilaggrin to filaggrin, which has been proposed based on ultrastructural and immunohistochemical studies.⁸

The differential diagnosis includes granular parakeratosis, intertrigo (caused by seborrheic dermatitis, candidiasis, inverse psoriasis, or erythrasma), Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, and irritant or allergic contact dermatitis. The papules may resemble seborrheic keratoses, while the plaques can be mistaken for acanthosis nigricans.

Therapeutic success has been reported with topical corticosteroids, vitamin D analogues, topical or oral retinoids, ammonium lactate, calcineurin inhibitors, topical or oral antifungals, cryotherapy, and botulinum toxin injections.^3,9-11 In addition, parakeratosis has decreased in biopsies from psoriatic patients after acitretin, methotrexate, and phototherapy, which may be alternative treatments for unusually difficult or recalcitrant cases of granular parakeratosis. To minimize side effects and resolve the papules quickly, we combined 2 synergistic agents—glycolic acid and tretinoin—each with different mechanisms of action, and we observed excellent clinical response.

Granular parakeratosis is possibly related to a combination of topical products that potentiate irritation, rubbing, and occlusion of sweat. Multiple treatment modalities likely contribute to clearing, the most important being removal of any triggering topical products. Our patient’s change in deodorant may have been the inciting factor for the disease. Withdrawal of the Secret Clinical Strength deodorant prompted clearing, though topical retinoid and glycolic acid acted as facilitating therapies for timely results. A thorough history, as highlighted by this case, may help pinpoint etiologic factors. By identifying a seemingly innocuous change in hygienic routine, we were able to minimize the need for ongoing therapy.

To the Editor:

A 46-year-old overweight woman presented with a rash in the axillae of 2 months’ duration. She did not report any additional symptoms such as pruritus or pain. She reported changing her deodorant recently from Secret Original to Secret Clinical Strength (both Procter & Gamble). Her medical history was remarkable for asthma and gastroesophageal reflux disease. Clinical examination revealed erythematous-brown, stuccolike, hyperkeratotic papules coalescing into plaques in recently shaved axillae, affecting the left axilla more than the right axilla (Figure 1). The clinical differential diagnosis included granular parakeratosis, intertrigo, Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, acanthosis nigricans, seborrheic keratoses, and irritant or allergic contact dermatitis. A punch biopsy revealed a marked compact parakeratotic horn with retention of keratohyalin granules (Figure 2). The subjacent epidermis showed some acanthosis and spongiosis with mild chronic inflammation of the dermal rim. Based on histopathology, granular parakeratosis was diagnosed.

At a subsequent visit 2 weeks later, we prescribed glycolic acid lotion 10% applied to the axillae twice daily, plus tretinoin gel 0.05% applied to the axillae each evening. She reported clearing after 1 week of therapy. She also had changed her deodorant from Secret Clinical Strength back to the usual Secret Original. The patient discontinued topical treatment after clearing of the lesions. Three weeks later, clinical examination revealed postinflammatory hyperpigmentation in the axillae, and the prior lesions had resolved (Figure 3).

The cause is unknown but possibly related to irritation from rubbing, occlusion, sweating, or deodorants.^5,7 Cases indicate a link to obesity. Hypotheses as to the etiology include the disruption of cornification. Normally, filaggrin maintains the keratohyaline granules in the stratum corneum during cornification. Therefore, the retention of keratohyaline granules in granular parakeratosis may be due to a defect in processing profilaggrin to filaggrin, which has been proposed based on ultrastructural and immunohistochemical studies.⁸

The differential diagnosis includes granular parakeratosis, intertrigo (caused by seborrheic dermatitis, candidiasis, inverse psoriasis, or erythrasma), Hailey-Hailey disease, Darier disease, pemphigus vegetans, confluent and reticulated papillomatosis, and irritant or allergic contact dermatitis. The papules may resemble seborrheic keratoses, while the plaques can be mistaken for acanthosis nigricans.

Therapeutic success has been reported with topical corticosteroids, vitamin D analogues, topical or oral retinoids, ammonium lactate, calcineurin inhibitors, topical or oral antifungals, cryotherapy, and botulinum toxin injections.^3,9-11 In addition, parakeratosis has decreased in biopsies from psoriatic patients after acitretin, methotrexate, and phototherapy, which may be alternative treatments for unusually difficult or recalcitrant cases of granular parakeratosis. To minimize side effects and resolve the papules quickly, we combined 2 synergistic agents—glycolic acid and tretinoin—each with different mechanisms of action, and we observed excellent clinical response.

Granular parakeratosis is possibly related to a combination of topical products that potentiate irritation, rubbing, and occlusion of sweat. Multiple treatment modalities likely contribute to clearing, the most important being removal of any triggering topical products. Our patient’s change in deodorant may have been the inciting factor for the disease. Withdrawal of the Secret Clinical Strength deodorant prompted clearing, though topical retinoid and glycolic acid acted as facilitating therapies for timely results. A thorough history, as highlighted by this case, may help pinpoint etiologic factors. By identifying a seemingly innocuous change in hygienic routine, we were able to minimize the need for ongoing therapy.

In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.

The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.

During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.

“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO₂ has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”

For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), randomly assigned the 62 patients with mild to moderate infraorbital dark circles to receive microneedling and 10% trichloroacetic acid peels or carbon dioxide laser resurfacing monthly for three consecutive sessions. They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.

In the carbon dioxide laser group, a Lutronic CO₂ laser was used with a pulse energy of 10 J/cm², a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.

The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).

Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.

“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.

The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.

During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.

“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO₂ has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”

For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), randomly assigned the 62 patients with mild to moderate infraorbital dark circles to receive microneedling and 10% trichloroacetic acid peels or carbon dioxide laser resurfacing monthly for three consecutive sessions. They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.

In the carbon dioxide laser group, a Lutronic CO₂ laser was used with a pulse energy of 10 J/cm², a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.

The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).

Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.

“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

In a study of patients with mild to moderate infraorbital dark circles, treatment with carbon dioxide laser resurfacing did not produce a significant improvement in infraorbital hyperpigmentation. However, the combination of microneedling and 10% trichloroacetic acid peels did.

The finding comes from what is believed to be the first head-to-head comparison of the two procedures for infraorbital dark circles, which are a common cosmetic concern with increased age.

During a late-breaking abstract session at the virtual annual meeting of the American Academy of Dermatology, lead study author Banu Farabi, MD, said that dark circles seen in the periorbital area are defined as bilateral, round homogeneous pigmented macules whose etiology is thought to be multifactorial. Available treatments include bleaching creams, topical retinoids, chemical peels, lasers, autologous fat transplantation, injectable fillers, and blepharoplasty.

“Microneedling has been recently suggested as an effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi said. “This technique is based on creating microchannels that can stimulate the production of subcutaneous collagen and elastin. It also enhances the revascularization and fibroblast activity, which increases the skin thickness and gives a shiny appearance to the skin. The fractional CO₂ has also been introduced as an effective procedure to remove infraorbital dark circles. However, there are some potential complications with that therapy.”

For the current study, Dr. Farabi, of the department of dermatology at Ankara (Turkey) University, and Mohamad Goldust, MD, of University Hospital Basel (Switzerland), randomly assigned the 62 patients with mild to moderate infraorbital dark circles to receive microneedling and 10% trichloroacetic acid peels or carbon dioxide laser resurfacing monthly for three consecutive sessions. They used the handheld Automatic Microneedle Therapy System-Handhold from MCure. After creating microchannels, the investigators topically applied 10% trichloroacetic acid peels to each infraorbital area and waited for 5 minutes.

In the carbon dioxide laser group, a Lutronic CO₂ laser was used with a pulse energy of 10 J/cm², a 100-microsecond pulse rate, 30 W of power, and a pulse width of 4 mm. The treatment outcome was assessed with the patient’s satisfaction and the physician’s judgment, which were no response, partial response, and complete response. Patients in both study groups were followed up for blinded-investigator assessment of infraorbital hyperpigmentation, adverse events, and improvement, compared with baseline.

The mean age of patients was 40 years, with a range between 27 and 58 years. About one-third of patients in each group had Fitzpatrick skin types II, III, and IV, respectively. In the blinded investigator assessment, the laser-resurfacing procedure did not demonstrate a significant improvement in infraorbital hyperpigmentation at day 90 (P = .24). However, the combination of microneedling and 10% trichloroacetic acid peels significantly improved infraorbital hyperpigmentation by day 90, with improvement maintained through day 180 (P = .012 and .002, respectively).

Adverse events were mild and temporary in both groups. In the laser-resurfacing group, 7 of the patients (22.5%) developed transient infraorbital hyperpigmentation postoperatively that lasted 4 weeks. In the combination treatment group, 18 patients (58%) developed transient erythema that lasted for up to 1 week.

“We suggest using microneedling plus 10% [trichloroacetic acid] as a cost-effective and efficient method for reducing infraorbital dark circles,” Dr. Farabi concluded.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

Dermatologic treatment of patients with skin of color offers specific challenges. Studies have reported structural, morphologic, and physiologic distinctions among different ethnic groups,¹ which may account for distinct clinical presentations of skin disease seen in patients with skin of color. Patients with skin of color are at increased risk for specific dermatologic conditions, such as postinflammatory hyperpigmentation, keloid development, and central centrifugal cicatricial alopecia.^2,3 Furthermore, although skin cancer is less prevalent in patients with skin of color, it often presents at a more advanced stage and with a worse prognosis compared to white patients.⁴

Individuals with skin of color make up the majority of the world’s population and a rapidly expanding portion of the US population. By the year 2044, more than half of all Americans are projected to belong to an ethnic group that is currently a minority. By 2060, the population of citizens identifying with 2 or more races will increase by 226%, the Asian population is projected to grow by 128%, the Hispanic population will increase by 115%, and the black population will increase by 42%.⁵ The racial and ethnic composition of the United States is evolving, and dermatologic care must evolve accordingly to address patients’ unique concerns. It is essential for future dermatologists to be knowledgeable about dermatologic conditions presenting in patients of various ethnic backgrounds.

Prior studies have demonstrated the need for increased exposure, education, and training in diseases pertaining to skin of color in US dermatology residency programs.^6-8 The aim of this study was to assess if dermatologists in-training feel that their residency curriculum sufficiently educates them on the needs of patients with skin of color.

Methods

A 10-question anonymous survey was emailed to 109 dermatology residency programs to evaluate the attitudes of dermatology residents about their exposure to patients with skin of color and their skin-of-color curriculum. The study included individuals 18 years or older who were current residents in a dermatology program accredited by the Accreditation Council for Graduate Medical Education. Responses were measured on a 1 to 3 Likert scale, ranging from agree, neutral, and disagree. Data were analyzed using the Fisher exact test, and the statistical significance was set at P<.05.

Results

Forty-three dermatology residents completed the survey. Respondents self-selected their regions, with 8 (19%) from the Northeast (NE), 7 (16%) from the Southeast (SE), 12 (28%) from the Midwest (MW), 8 (19%) from the Southwest (SW), and 8 (18%) from the Northwest (NW)(Table 1). Overall, 31 (72%) respondents agreed that their practice treats a diverse patient population. Respondents who agreed most often were from the NE, SE, and SW. Less than two-thirds of respondents from the MW agreed, and only half of respondents from the NW agreed (Table 2). Although 37% of all respondents agreed that a dedicated multiethnic skin clinic is important for residents, 5 (63%) NE residents disagreed with this statement compared to 5 (42%) MW residents and 5 (63%) NW residents who agreed (P<.005). Overall, 39 (91%) respondents agreed that dedicated lectures on skin conditions in skin of color patients are important to gain competence in treating patients. Only 4 respondents were neutral to this question, 2 (17%) MW residents and 2 (25%) SW residents. When asked if reading textbook chapters on multiethnic skin is important to gain competence, 36 (83%) respondents agreed. Two respondents disagreed, 1 (13%) from the NE and 1 (8%) from the MW. Overall, 23% of respondents agreed that a rotation dedicated to skin of color is important to build competency. There was a significant difference in responses between the NE and MW (P=.032) and between the NE and NW (P=.019). Furthermore, 19 (44%) respondents agreed that having a faculty member or departmental expert is important for residents to gain competence in treating conditions affecting skin of color. Again, there was a significant difference in responses between the NE and MW (P=.003) and between the SE and MW (P=.009).

When asked the number of hours of lecture per month necessary to gain competence in conditions affecting patients with skin of color, 67% agreed that 1 to 5 hours was sufficient (Table 3). There were significant differences in the responses between the NE and SE (P=.024) and the SE and MW (P=.007). Of all respondents, 53% reported 1 to 5 months of clinical training are needed to gain competence in treating conditions affecting patients with skin of color, with significant differences in responses between the NE and MW (P<.001), the NE and SW (P=.019), and the SE and MW (P=.015)(Table 4).

Comment

Responses varied by practicing region. Less ethnically diverse regions, such as the MW and NW, were more likely to agree that dedicated clinics and rotations are important to gain competence compared to more ethnically diverse regions such as the NE, SE, and SW. Overall, more residents reported that dedicated lectures and textbook chapters were important to gain competency compared to dedicated clinics or rotations.

Although interactive lectures and textbook readings are important for obtaining a foundational understanding of dermatologic disease, they cannot substitute for clinical interactions and hands-on experience treating patients with skin of color.⁹ Not only do clinical interactions encourage independent reading and the study of encountered diagnoses, but intercommunication with patients may have a more profound and lasting impact on residents’ education.

Different regions of the United States have varying distributions of patients with skin of color, and dermatology residency program training reflects these disparities.⁶ In areas of less diversity, dermatology residents examine, diagnose, and treat substantially fewer patients with skin of color. The desire for more diverse training supports the prior findings of Nijhawan et al⁶ and is reflected in the responses we received in our study, whereby residents from the less ethnically diversified regions of the MW and NW were more likely to agree that clinics and rotations were necessary for training in preparation to sufficiently address the needs of patients with skin of color.

One way to compensate for the lack of ethnic diversity encountered in areas such as the MW and NW would be to develop educational programs featuring experts on skin of color.⁶ These specialists would not only train dermatology residents in areas of the country currently lacking ethnic diversity but also expand the expertise for treating patients with skin of color. Additionally, dedicated multiethnic skin clinics and externships devoted solely to treating patients with skin of color could be encouraged for residency training.⁶ Finally, community outreach through volunteer clinics may provide residents exposure to patients with skin of color seeking dermatologic care.¹⁰

This study was limited by the small number of respondents, but we were able to extract important trends and data from the collected responses. It is possible that respondents felt strongly about topics involving patients with skin of color, and the results were skewed to reflect individual bias. Additional limitations included not asking respondents for program names and population density (eg, urban, suburban, rural). Future studies should be directed toward analyzing how the diversity of the local population influences training in patients with skin of color, comparing program directors’ perceptions with residents’ perceptions on training in skin of color, and assessing patient perception of residents’ training in skin of color.

Conclusion

In the last decade it has become increasingly apparent that the US population is diversifying and that patients with skin of color will comprise a substantial proportion of the future population,^8,11 which emphasizes the need for dermatology residency programs to ensure that residents receive adequate training and exposure to patients with skin of color as well as the distinct skin diseases seen more commonly in these populations.¹²

Dermatologic treatment of patients with skin of color offers specific challenges. Studies have reported structural, morphologic, and physiologic distinctions among different ethnic groups,¹ which may account for distinct clinical presentations of skin disease seen in patients with skin of color. Patients with skin of color are at increased risk for specific dermatologic conditions, such as postinflammatory hyperpigmentation, keloid development, and central centrifugal cicatricial alopecia.^2,3 Furthermore, although skin cancer is less prevalent in patients with skin of color, it often presents at a more advanced stage and with a worse prognosis compared to white patients.⁴

Individuals with skin of color make up the majority of the world’s population and a rapidly expanding portion of the US population. By the year 2044, more than half of all Americans are projected to belong to an ethnic group that is currently a minority. By 2060, the population of citizens identifying with 2 or more races will increase by 226%, the Asian population is projected to grow by 128%, the Hispanic population will increase by 115%, and the black population will increase by 42%.⁵ The racial and ethnic composition of the United States is evolving, and dermatologic care must evolve accordingly to address patients’ unique concerns. It is essential for future dermatologists to be knowledgeable about dermatologic conditions presenting in patients of various ethnic backgrounds.

Prior studies have demonstrated the need for increased exposure, education, and training in diseases pertaining to skin of color in US dermatology residency programs.^6-8 The aim of this study was to assess if dermatologists in-training feel that their residency curriculum sufficiently educates them on the needs of patients with skin of color.

Methods

A 10-question anonymous survey was emailed to 109 dermatology residency programs to evaluate the attitudes of dermatology residents about their exposure to patients with skin of color and their skin-of-color curriculum. The study included individuals 18 years or older who were current residents in a dermatology program accredited by the Accreditation Council for Graduate Medical Education. Responses were measured on a 1 to 3 Likert scale, ranging from agree, neutral, and disagree. Data were analyzed using the Fisher exact test, and the statistical significance was set at P<.05.

Results

Forty-three dermatology residents completed the survey. Respondents self-selected their regions, with 8 (19%) from the Northeast (NE), 7 (16%) from the Southeast (SE), 12 (28%) from the Midwest (MW), 8 (19%) from the Southwest (SW), and 8 (18%) from the Northwest (NW)(Table 1). Overall, 31 (72%) respondents agreed that their practice treats a diverse patient population. Respondents who agreed most often were from the NE, SE, and SW. Less than two-thirds of respondents from the MW agreed, and only half of respondents from the NW agreed (Table 2). Although 37% of all respondents agreed that a dedicated multiethnic skin clinic is important for residents, 5 (63%) NE residents disagreed with this statement compared to 5 (42%) MW residents and 5 (63%) NW residents who agreed (P<.005). Overall, 39 (91%) respondents agreed that dedicated lectures on skin conditions in skin of color patients are important to gain competence in treating patients. Only 4 respondents were neutral to this question, 2 (17%) MW residents and 2 (25%) SW residents. When asked if reading textbook chapters on multiethnic skin is important to gain competence, 36 (83%) respondents agreed. Two respondents disagreed, 1 (13%) from the NE and 1 (8%) from the MW. Overall, 23% of respondents agreed that a rotation dedicated to skin of color is important to build competency. There was a significant difference in responses between the NE and MW (P=.032) and between the NE and NW (P=.019). Furthermore, 19 (44%) respondents agreed that having a faculty member or departmental expert is important for residents to gain competence in treating conditions affecting skin of color. Again, there was a significant difference in responses between the NE and MW (P=.003) and between the SE and MW (P=.009).

When asked the number of hours of lecture per month necessary to gain competence in conditions affecting patients with skin of color, 67% agreed that 1 to 5 hours was sufficient (Table 3). There were significant differences in the responses between the NE and SE (P=.024) and the SE and MW (P=.007). Of all respondents, 53% reported 1 to 5 months of clinical training are needed to gain competence in treating conditions affecting patients with skin of color, with significant differences in responses between the NE and MW (P<.001), the NE and SW (P=.019), and the SE and MW (P=.015)(Table 4).

Comment

Responses varied by practicing region. Less ethnically diverse regions, such as the MW and NW, were more likely to agree that dedicated clinics and rotations are important to gain competence compared to more ethnically diverse regions such as the NE, SE, and SW. Overall, more residents reported that dedicated lectures and textbook chapters were important to gain competency compared to dedicated clinics or rotations.

Although interactive lectures and textbook readings are important for obtaining a foundational understanding of dermatologic disease, they cannot substitute for clinical interactions and hands-on experience treating patients with skin of color.⁹ Not only do clinical interactions encourage independent reading and the study of encountered diagnoses, but intercommunication with patients may have a more profound and lasting impact on residents’ education.

Different regions of the United States have varying distributions of patients with skin of color, and dermatology residency program training reflects these disparities.⁶ In areas of less diversity, dermatology residents examine, diagnose, and treat substantially fewer patients with skin of color. The desire for more diverse training supports the prior findings of Nijhawan et al⁶ and is reflected in the responses we received in our study, whereby residents from the less ethnically diversified regions of the MW and NW were more likely to agree that clinics and rotations were necessary for training in preparation to sufficiently address the needs of patients with skin of color.

One way to compensate for the lack of ethnic diversity encountered in areas such as the MW and NW would be to develop educational programs featuring experts on skin of color.⁶ These specialists would not only train dermatology residents in areas of the country currently lacking ethnic diversity but also expand the expertise for treating patients with skin of color. Additionally, dedicated multiethnic skin clinics and externships devoted solely to treating patients with skin of color could be encouraged for residency training.⁶ Finally, community outreach through volunteer clinics may provide residents exposure to patients with skin of color seeking dermatologic care.¹⁰

This study was limited by the small number of respondents, but we were able to extract important trends and data from the collected responses. It is possible that respondents felt strongly about topics involving patients with skin of color, and the results were skewed to reflect individual bias. Additional limitations included not asking respondents for program names and population density (eg, urban, suburban, rural). Future studies should be directed toward analyzing how the diversity of the local population influences training in patients with skin of color, comparing program directors’ perceptions with residents’ perceptions on training in skin of color, and assessing patient perception of residents’ training in skin of color.

Conclusion

In the last decade it has become increasingly apparent that the US population is diversifying and that patients with skin of color will comprise a substantial proportion of the future population,^8,11 which emphasizes the need for dermatology residency programs to ensure that residents receive adequate training and exposure to patients with skin of color as well as the distinct skin diseases seen more commonly in these populations.¹²

Dermatologic treatment of patients with skin of color offers specific challenges. Studies have reported structural, morphologic, and physiologic distinctions among different ethnic groups,¹ which may account for distinct clinical presentations of skin disease seen in patients with skin of color. Patients with skin of color are at increased risk for specific dermatologic conditions, such as postinflammatory hyperpigmentation, keloid development, and central centrifugal cicatricial alopecia.^2,3 Furthermore, although skin cancer is less prevalent in patients with skin of color, it often presents at a more advanced stage and with a worse prognosis compared to white patients.⁴

Individuals with skin of color make up the majority of the world’s population and a rapidly expanding portion of the US population. By the year 2044, more than half of all Americans are projected to belong to an ethnic group that is currently a minority. By 2060, the population of citizens identifying with 2 or more races will increase by 226%, the Asian population is projected to grow by 128%, the Hispanic population will increase by 115%, and the black population will increase by 42%.⁵ The racial and ethnic composition of the United States is evolving, and dermatologic care must evolve accordingly to address patients’ unique concerns. It is essential for future dermatologists to be knowledgeable about dermatologic conditions presenting in patients of various ethnic backgrounds.

Prior studies have demonstrated the need for increased exposure, education, and training in diseases pertaining to skin of color in US dermatology residency programs.^6-8 The aim of this study was to assess if dermatologists in-training feel that their residency curriculum sufficiently educates them on the needs of patients with skin of color.

Methods

A 10-question anonymous survey was emailed to 109 dermatology residency programs to evaluate the attitudes of dermatology residents about their exposure to patients with skin of color and their skin-of-color curriculum. The study included individuals 18 years or older who were current residents in a dermatology program accredited by the Accreditation Council for Graduate Medical Education. Responses were measured on a 1 to 3 Likert scale, ranging from agree, neutral, and disagree. Data were analyzed using the Fisher exact test, and the statistical significance was set at P<.05.

Results

Forty-three dermatology residents completed the survey. Respondents self-selected their regions, with 8 (19%) from the Northeast (NE), 7 (16%) from the Southeast (SE), 12 (28%) from the Midwest (MW), 8 (19%) from the Southwest (SW), and 8 (18%) from the Northwest (NW)(Table 1). Overall, 31 (72%) respondents agreed that their practice treats a diverse patient population. Respondents who agreed most often were from the NE, SE, and SW. Less than two-thirds of respondents from the MW agreed, and only half of respondents from the NW agreed (Table 2). Although 37% of all respondents agreed that a dedicated multiethnic skin clinic is important for residents, 5 (63%) NE residents disagreed with this statement compared to 5 (42%) MW residents and 5 (63%) NW residents who agreed (P<.005). Overall, 39 (91%) respondents agreed that dedicated lectures on skin conditions in skin of color patients are important to gain competence in treating patients. Only 4 respondents were neutral to this question, 2 (17%) MW residents and 2 (25%) SW residents. When asked if reading textbook chapters on multiethnic skin is important to gain competence, 36 (83%) respondents agreed. Two respondents disagreed, 1 (13%) from the NE and 1 (8%) from the MW. Overall, 23% of respondents agreed that a rotation dedicated to skin of color is important to build competency. There was a significant difference in responses between the NE and MW (P=.032) and between the NE and NW (P=.019). Furthermore, 19 (44%) respondents agreed that having a faculty member or departmental expert is important for residents to gain competence in treating conditions affecting skin of color. Again, there was a significant difference in responses between the NE and MW (P=.003) and between the SE and MW (P=.009).

When asked the number of hours of lecture per month necessary to gain competence in conditions affecting patients with skin of color, 67% agreed that 1 to 5 hours was sufficient (Table 3). There were significant differences in the responses between the NE and SE (P=.024) and the SE and MW (P=.007). Of all respondents, 53% reported 1 to 5 months of clinical training are needed to gain competence in treating conditions affecting patients with skin of color, with significant differences in responses between the NE and MW (P<.001), the NE and SW (P=.019), and the SE and MW (P=.015)(Table 4).

Comment

Responses varied by practicing region. Less ethnically diverse regions, such as the MW and NW, were more likely to agree that dedicated clinics and rotations are important to gain competence compared to more ethnically diverse regions such as the NE, SE, and SW. Overall, more residents reported that dedicated lectures and textbook chapters were important to gain competency compared to dedicated clinics or rotations.

Although interactive lectures and textbook readings are important for obtaining a foundational understanding of dermatologic disease, they cannot substitute for clinical interactions and hands-on experience treating patients with skin of color.⁹ Not only do clinical interactions encourage independent reading and the study of encountered diagnoses, but intercommunication with patients may have a more profound and lasting impact on residents’ education.

Different regions of the United States have varying distributions of patients with skin of color, and dermatology residency program training reflects these disparities.⁶ In areas of less diversity, dermatology residents examine, diagnose, and treat substantially fewer patients with skin of color. The desire for more diverse training supports the prior findings of Nijhawan et al⁶ and is reflected in the responses we received in our study, whereby residents from the less ethnically diversified regions of the MW and NW were more likely to agree that clinics and rotations were necessary for training in preparation to sufficiently address the needs of patients with skin of color.

One way to compensate for the lack of ethnic diversity encountered in areas such as the MW and NW would be to develop educational programs featuring experts on skin of color.⁶ These specialists would not only train dermatology residents in areas of the country currently lacking ethnic diversity but also expand the expertise for treating patients with skin of color. Additionally, dedicated multiethnic skin clinics and externships devoted solely to treating patients with skin of color could be encouraged for residency training.⁶ Finally, community outreach through volunteer clinics may provide residents exposure to patients with skin of color seeking dermatologic care.¹⁰

This study was limited by the small number of respondents, but we were able to extract important trends and data from the collected responses. It is possible that respondents felt strongly about topics involving patients with skin of color, and the results were skewed to reflect individual bias. Additional limitations included not asking respondents for program names and population density (eg, urban, suburban, rural). Future studies should be directed toward analyzing how the diversity of the local population influences training in patients with skin of color, comparing program directors’ perceptions with residents’ perceptions on training in skin of color, and assessing patient perception of residents’ training in skin of color.

Conclusion

In the last decade it has become increasingly apparent that the US population is diversifying and that patients with skin of color will comprise a substantial proportion of the future population,^8,11 which emphasizes the need for dermatology residency programs to ensure that residents receive adequate training and exposure to patients with skin of color as well as the distinct skin diseases seen more commonly in these populations.¹²

To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 (jessdawsonmed@gmail.com).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 (jessdawsonmed@gmail.com).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 (jessdawsonmed@gmail.com).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

The Diagnosis: Pseudo-Black Hairy Tongue

Pseudo-black hairy tongue is a benign and painless disorder characterized by transient hyperpigmentation of the tongue with a substance that can be easily scraped off. In this case, the patient's lingual discoloration was secondary to the ingestion of bismuth salicylate. The phenomenon is thought to occur due to a reaction between bismuth and sulfur-containing compounds in the saliva, resulting in the characteristic black substance on the surface of the tongue that nestles between the lingual papillae.¹ An associated feature may include black stools. Other etiologic factors involved in pseudo-black hairy tongue include food coloring, tobacco, and other drugs such antibiotics and antidepressants.²  

The differential diagnosis of lingual hyperpigmentation includes lingua villosa nigra (also known as black hairy tongue), pigmented fungiform papillae of the tongue, acanthosis nigricans, and oral hairy leukoplakia. Lingua villosa nigra is a similar condition in which individuals present with a black tongue; however, the tongue also appears hairy. The tongue may appear as other colors such as brown, yellow, or green. Patients additionally may have symptoms of burning, dysgeusia, halitosis, or gagging. Poor oral hygiene, xerostomia, use of tobacco or alcohol, and different medications including antibiotics and antipsychotic medications increase the risk for developing lingua villosa nigra.^2,3 This condition is distinguished from pseudo-black hairy tongue by proliferation and elongation of the filiform papillae.³ Pigmented fungiform papillae of the tongue is a normal variant of tongue morphology, is more common in individuals with darker skin types, and primarily affects the lateral aspect and apex of the tongue.⁴ Acanthosis nigricans can appear in the oral cavity as multiple pigmented papillary lesions on the dorsal and lateral regions of the tongue and frequently involves the lips; this condition may be associated with metabolic disorders or underlying malignancy.^2,3 Oral hairy leukoplakia is caused by Epstein-Barr virus infection and typically presents as white plaques on the dorsal and ventral surfaces of the tongue; this condition largely is found in immunocompromised patients.⁵

In our patient there was an acute onset of tongue discoloration associated with ingestion of bismuth salicylate, no hypertrophy or lengthening of the lingual papillae, and no involvement of the patient's lips, which was consistent with the diagnosis of pseudo-black hairy tongue. Pseudo-black hairy tongue is transient and treated by discontinuation of offending agents and proper hygiene practices.

To the Editor:

The use of sunless tanners has become an alternative for individuals who wish to have tan skin without exposure to UV radiation.¹ We present a case of a patient who experienced persistent hyperpigmented patches on the hands months after the use of a sunless tanner containing dihydroxyacetone (DHA), a carbohydrate that reacts with amino acids in the stratum corneum to produce pigments called melanoidins. The hyperpigmentation caused by DHA is due to the Maillard reaction, which is the nonenzymatic glycation of amino groups of proteins by the carbonyl groups of sugar.² Many sunless tanners contain DHA at varying concentrations. Dermatologists should be aware of the benefits and potential side effects of these alternative products so that they can appropriately counsel patients.

A 20-year-old woman with no history of skin disease presented for evaluation of hyperpigmented patches on the dorsal hands of several months’ duration. Physical examination revealed ill-defined hyperpigmented patches on the dorsal fingers without associated scale or erythema (Figure 1). She had a remote history of Hodgkin lymphoma treated with chemotherapy and was in remission for 5 years prior to the current presentation. Her hematologists referred her to dermatology for evaluation, as they did not believe the patches could be related to her chemotherapy given that she had completed the treatment years before.

Products with DHA only confer a sun protection factor of approximately 3⁴; although patients may appear tan, they have no actual decreased risk for sunburn after use. Reports have shown that the use of sunless tanners containing DHA can alter the appearance of melanocytic lesions clinically and has caused pseudochromhidrosis on the palms.^3,5,6 A study performed on a human keratinocyte cell line, HaCaT, showed that DHA can induce DNA damage, cell-cycle block, and apoptosis.⁷ In addition, as described in our case, patients may experience prolonged hyperpigmentation after use.

This case demonstrates the potential for persistent hyperpigmentation months after the use of sunless tanners containing DHA. Asking patients specific questions regarding their history of tanning product use is essential in identifying the pathology. Although a skin biopsy may not be strictly indicated, it may aid diagnosis, especially when the history is unclear. As more dermatologists support the use of sunless tanner, we must be aware of this possible outcome, especially on more cosmetically sensitive areas such as the fingers in this patient. Clinicians should be aware that the US Food and Drug Administration recommends avoiding contact with mucous membranes when applying products containing DHA and also recommends use of a test spot prior to treating the entire body with the product.⁸ Patients must not only be educated on the benefits of using sunless tanners but on the potential side effects with use of these products as well.

To the Editor:

The use of sunless tanners has become an alternative for individuals who wish to have tan skin without exposure to UV radiation.¹ We present a case of a patient who experienced persistent hyperpigmented patches on the hands months after the use of a sunless tanner containing dihydroxyacetone (DHA), a carbohydrate that reacts with amino acids in the stratum corneum to produce pigments called melanoidins. The hyperpigmentation caused by DHA is due to the Maillard reaction, which is the nonenzymatic glycation of amino groups of proteins by the carbonyl groups of sugar.² Many sunless tanners contain DHA at varying concentrations. Dermatologists should be aware of the benefits and potential side effects of these alternative products so that they can appropriately counsel patients.

A 20-year-old woman with no history of skin disease presented for evaluation of hyperpigmented patches on the dorsal hands of several months’ duration. Physical examination revealed ill-defined hyperpigmented patches on the dorsal fingers without associated scale or erythema (Figure 1). She had a remote history of Hodgkin lymphoma treated with chemotherapy and was in remission for 5 years prior to the current presentation. Her hematologists referred her to dermatology for evaluation, as they did not believe the patches could be related to her chemotherapy given that she had completed the treatment years before.

Products with DHA only confer a sun protection factor of approximately 3⁴; although patients may appear tan, they have no actual decreased risk for sunburn after use. Reports have shown that the use of sunless tanners containing DHA can alter the appearance of melanocytic lesions clinically and has caused pseudochromhidrosis on the palms.^3,5,6 A study performed on a human keratinocyte cell line, HaCaT, showed that DHA can induce DNA damage, cell-cycle block, and apoptosis.⁷ In addition, as described in our case, patients may experience prolonged hyperpigmentation after use.

This case demonstrates the potential for persistent hyperpigmentation months after the use of sunless tanners containing DHA. Asking patients specific questions regarding their history of tanning product use is essential in identifying the pathology. Although a skin biopsy may not be strictly indicated, it may aid diagnosis, especially when the history is unclear. As more dermatologists support the use of sunless tanner, we must be aware of this possible outcome, especially on more cosmetically sensitive areas such as the fingers in this patient. Clinicians should be aware that the US Food and Drug Administration recommends avoiding contact with mucous membranes when applying products containing DHA and also recommends use of a test spot prior to treating the entire body with the product.⁸ Patients must not only be educated on the benefits of using sunless tanners but on the potential side effects with use of these products as well.

To the Editor:

The use of sunless tanners has become an alternative for individuals who wish to have tan skin without exposure to UV radiation.¹ We present a case of a patient who experienced persistent hyperpigmented patches on the hands months after the use of a sunless tanner containing dihydroxyacetone (DHA), a carbohydrate that reacts with amino acids in the stratum corneum to produce pigments called melanoidins. The hyperpigmentation caused by DHA is due to the Maillard reaction, which is the nonenzymatic glycation of amino groups of proteins by the carbonyl groups of sugar.² Many sunless tanners contain DHA at varying concentrations. Dermatologists should be aware of the benefits and potential side effects of these alternative products so that they can appropriately counsel patients.

A 20-year-old woman with no history of skin disease presented for evaluation of hyperpigmented patches on the dorsal hands of several months’ duration. Physical examination revealed ill-defined hyperpigmented patches on the dorsal fingers without associated scale or erythema (Figure 1). She had a remote history of Hodgkin lymphoma treated with chemotherapy and was in remission for 5 years prior to the current presentation. Her hematologists referred her to dermatology for evaluation, as they did not believe the patches could be related to her chemotherapy given that she had completed the treatment years before.

Products with DHA only confer a sun protection factor of approximately 3⁴; although patients may appear tan, they have no actual decreased risk for sunburn after use. Reports have shown that the use of sunless tanners containing DHA can alter the appearance of melanocytic lesions clinically and has caused pseudochromhidrosis on the palms.^3,5,6 A study performed on a human keratinocyte cell line, HaCaT, showed that DHA can induce DNA damage, cell-cycle block, and apoptosis.⁷ In addition, as described in our case, patients may experience prolonged hyperpigmentation after use.

This case demonstrates the potential for persistent hyperpigmentation months after the use of sunless tanners containing DHA. Asking patients specific questions regarding their history of tanning product use is essential in identifying the pathology. Although a skin biopsy may not be strictly indicated, it may aid diagnosis, especially when the history is unclear. As more dermatologists support the use of sunless tanner, we must be aware of this possible outcome, especially on more cosmetically sensitive areas such as the fingers in this patient. Clinicians should be aware that the US Food and Drug Administration recommends avoiding contact with mucous membranes when applying products containing DHA and also recommends use of a test spot prior to treating the entire body with the product.⁸ Patients must not only be educated on the benefits of using sunless tanners but on the potential side effects with use of these products as well.

The histopathologic diagnosis of vitiligo is classically understood as the absence of melanocytes and melanin in the skin biopsy.¹ It is difficult for a pathologist to establish the absolute absence of melanocytes and melanin in a skin biopsy. Therefore, we need to take into consideration many variables when we face the possibility to biopsy a vitiligo lesion.

The basis of the clinical diagnosis of vitiligo is the appearance of achromic lesions in periorificial and acral areas; however, sometimes it is difficult to differentiate between an achromic or hypochromic lesion. Although Wood light is of great help in these circumstances, it still can be difficult to make the diagnosis with certainty.

In other cases, the lesions do not present a classic distribution of vitiligo, and other differential diagnoses are considered. For example, if we see a single hypochromic or achromic lesion in a young child, then the main differential diagnosis would be achromic nevus. If there are multiple lesions, then we may consider progressive macular hypomelanosis, postinflammatory hypopigmentation, and hypopigmented mycosis fungoides. In genital lesions, the differential diagnosis between initial lichen sclerosus and vitiligo also can be considered. Finally, we must always bear in mind that both sarcoidosis and Hansen disease can appear as achromic or hypochromic lesions.

The histologic diagnosis of vitiligo in a completely constituted lesion implies the total loss of melanocytes and melanin in the epidermis. Additional histologic findings are described at the edge of the advanced border, such as the presence of melanocytes that have increased in size with large dendrites and lymphoid infiltrate. In perilesional skin, vacuolated keratinocytes and Langerhans cells have increased in number and repositioned in the basal layer, with visible degeneration of nerves and sweat glands. Lymphocytes also can be found in contact with the melanocytes.² It is important to note that in addition to these histologic findings, it is common to find spongiosis, mononuclear superficial perivascular inflammatory infiltrate, and melanophages in biopsies of vitiligo.³

Given that ensuring the absence of melanocytes is central to diagnosis and melanocytes can be difficult to identify or differentiate from repositioned Langerhans cells in the basal layer with hematoxylin and eosin stain, immunohistochemical techniques must be performed every time we are dealing with vitiligo biopsies. Although there are no studies comparing the diagnostic value of the different immunohistochemical techniques in vitiligo, dihydroxyphenylalanine (DOPA) seems to be a good option, as it will only mark active melanocytes. Human melanoma black 45 (HMB-45), anti-TYRP1 (Mel-5), and antimelanoma gp 100 antibody (NKI/beteb) also have been used. Some authors recommend the use of pan melanoma because it includes 3 markers—HMB-45, tyrosinase, and Mart-1. Currently, SRY-related HMG-box10 (SOX10) seems to be a good option, as it is a nuclear marker that makes it easier to differentiate melanocytes from pigmented keratinocytes.⁴

Establishing a complete absence of melanocytes in the lesions or finding there are melanocytes but they are inactivated is key to evaluating the pathogenesis of vitiligo and directly affects the histologic diagnosis and eventually even the treatment. Le Poole et al⁵ used a panel of 17 monoclonal antibodies and a polyclonal antibody in lesions of 12 patients with vitiligo without identifying the presence of melanocytes. They concluded that there are no melanocytes in lesions of vitiligo.⁵

In a subsequent study with a larger number of patients, Kim et al² found melanocytes that marked with NKI/beteb and Mart-1 in 12 of 100 patients with vitiligo. They also showed melanocytes by electron microscopy in lesional skin of 1 of 3 patients with vitiligo.² Tobin et al⁶ managed to grow melanocytes from skin with vitiligo and confirmed the presence of melanin in basal keratinocytes of lesions of stable vitiligo. From this evidence we can conclude that the absence of melanocytes and melanin in the epidermis confirms the diagnosis of vitiligo; however, the opposite is not true—that is, the presence of melanocytes or melanin in a skin biopsy does not rule out the diagnosis of vitiligo.

Taking this information into consideration, we can understand that if our differential diagnosis is a dermatosis that requires the evaluation of the number of melanocytes as a fundamental diagnostic clue (eg, postinflammatory hypopigmentation), the biopsy will probably not be useful. On the other hand, when our differential diagnosis has characteristic diagnostic findings independent of the number of melanocytes or the presence of melanin, the biopsy will be useful (eg, hypopigmented mycosis fungoides).

Thus, we can understand why the histologic differentiation between vitiligo, pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation is difficult. The histology images of these 4 diseases may show different degrees of melanocyte and melanin decrease, spongiosis, and in the superficial dermis melanophages and mononuclear inflammatory infiltrate.⁷

Nevus depigmentosus also may generate diagnostic confusion with vitiligo. Although it is unilateral and usually congenital, it can appear as late as 3 years of age, leading to an initial clinical differential diagnosis of vitiligo. The histologic findings in this nevus also overlap with vitiligo. The characteristic findings are presence of melanocytes and decreased pigment in the keratinocytes compared with perilesional skin. Therefore, a biopsy is not a solution to this diagnostic dilemma.⁸

In all the differentials named, the solution to the diagnostic doubt is not based on the histologic findings but on the clinical evolution of the patients. In cases of vitiligo, the lesions will become more evident in the evolution. They will eventually disappear in pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation and will remain unchanged in nevus depigmentosus. It is important, especially when we are dealing with concerned parents/guardians, to convey the importance of assessing the evolution of the disease as the main diagnostic procedure. Even though a biopsy is minimally invasive, it is usually stressful on children, it may leave sequelae, and above all it will not contribute to the diagnosis in this clinical context.

There are other clinical circumstances in the scenario of hypochromic or achromic lesions in which the biopsy will be useful: If we consider an initial genital lichen sclerosus vs vitiligo. In lichen sclerosus the biopsy will show dermal hyalinosis and interphase changes; absence of both will support vitiligo. If we need to differentiate hypopigmented mycosis fungoides from vitiligo, we will find an infiltrate of pleomorphic lymphocytes in the epidermis and dermis in the former and an absence of these findings in vitiligo. Finally, if we find granulomas in a biopsy of an achromic or hypopigmented lesion, we may be dealing with hypopigmented sarcoidosis or Hansen disease.

It also is important to choose the best site to perform the biopsy to have the best chance at diagnosing vitiligo histologically. As already described, in the edges and in the perilesional skin we can find remnant melanocytes, Langerhans cells, and interphase changes that do not allow us to clearly evaluate the main change that is the loss of melanocytes and melanin. In fact, a biopsy of the edge of a vitiligo macula can lead to confusion. For example, if the differential diagnosis is lichen sclerosus and the image we see in the biopsy of the edge of a vitiligo lesion is an interface reaction, we can interpret it as a finding that favors lichen sclerosus. In this way, it is better to biopsy the center of a well-constituted vitiligo lesion where we have the best chance to assess the absence of melanin and melanocytes.

The vitiligo differential diagnosis can be divided into 2 groups: entities that are difficult to differentiate from vitiligo histologically (ie, pityriasis alba, postinflammatory hypopigmentation, progressive macular hypopigmentation, nevus depigmentosus) and entities that are easily distinguishable from vitiligo histologically (ie, lichen sclerosus, mycosis fungoides, sarcoidosis, leprosy). If our differential diagnosis was found in the first group, the final diagnosis should be based on the evolution of the patient. If it was in the second group, a biopsy of the center of the lesion will be useful and may allow us to reach a definitive diagnosis.

The histopathologic diagnosis of vitiligo is classically understood as the absence of melanocytes and melanin in the skin biopsy.¹ It is difficult for a pathologist to establish the absolute absence of melanocytes and melanin in a skin biopsy. Therefore, we need to take into consideration many variables when we face the possibility to biopsy a vitiligo lesion.

The basis of the clinical diagnosis of vitiligo is the appearance of achromic lesions in periorificial and acral areas; however, sometimes it is difficult to differentiate between an achromic or hypochromic lesion. Although Wood light is of great help in these circumstances, it still can be difficult to make the diagnosis with certainty.

In other cases, the lesions do not present a classic distribution of vitiligo, and other differential diagnoses are considered. For example, if we see a single hypochromic or achromic lesion in a young child, then the main differential diagnosis would be achromic nevus. If there are multiple lesions, then we may consider progressive macular hypomelanosis, postinflammatory hypopigmentation, and hypopigmented mycosis fungoides. In genital lesions, the differential diagnosis between initial lichen sclerosus and vitiligo also can be considered. Finally, we must always bear in mind that both sarcoidosis and Hansen disease can appear as achromic or hypochromic lesions.

The histologic diagnosis of vitiligo in a completely constituted lesion implies the total loss of melanocytes and melanin in the epidermis. Additional histologic findings are described at the edge of the advanced border, such as the presence of melanocytes that have increased in size with large dendrites and lymphoid infiltrate. In perilesional skin, vacuolated keratinocytes and Langerhans cells have increased in number and repositioned in the basal layer, with visible degeneration of nerves and sweat glands. Lymphocytes also can be found in contact with the melanocytes.² It is important to note that in addition to these histologic findings, it is common to find spongiosis, mononuclear superficial perivascular inflammatory infiltrate, and melanophages in biopsies of vitiligo.³

Given that ensuring the absence of melanocytes is central to diagnosis and melanocytes can be difficult to identify or differentiate from repositioned Langerhans cells in the basal layer with hematoxylin and eosin stain, immunohistochemical techniques must be performed every time we are dealing with vitiligo biopsies. Although there are no studies comparing the diagnostic value of the different immunohistochemical techniques in vitiligo, dihydroxyphenylalanine (DOPA) seems to be a good option, as it will only mark active melanocytes. Human melanoma black 45 (HMB-45), anti-TYRP1 (Mel-5), and antimelanoma gp 100 antibody (NKI/beteb) also have been used. Some authors recommend the use of pan melanoma because it includes 3 markers—HMB-45, tyrosinase, and Mart-1. Currently, SRY-related HMG-box10 (SOX10) seems to be a good option, as it is a nuclear marker that makes it easier to differentiate melanocytes from pigmented keratinocytes.⁴

Establishing a complete absence of melanocytes in the lesions or finding there are melanocytes but they are inactivated is key to evaluating the pathogenesis of vitiligo and directly affects the histologic diagnosis and eventually even the treatment. Le Poole et al⁵ used a panel of 17 monoclonal antibodies and a polyclonal antibody in lesions of 12 patients with vitiligo without identifying the presence of melanocytes. They concluded that there are no melanocytes in lesions of vitiligo.⁵

In a subsequent study with a larger number of patients, Kim et al² found melanocytes that marked with NKI/beteb and Mart-1 in 12 of 100 patients with vitiligo. They also showed melanocytes by electron microscopy in lesional skin of 1 of 3 patients with vitiligo.² Tobin et al⁶ managed to grow melanocytes from skin with vitiligo and confirmed the presence of melanin in basal keratinocytes of lesions of stable vitiligo. From this evidence we can conclude that the absence of melanocytes and melanin in the epidermis confirms the diagnosis of vitiligo; however, the opposite is not true—that is, the presence of melanocytes or melanin in a skin biopsy does not rule out the diagnosis of vitiligo.

Taking this information into consideration, we can understand that if our differential diagnosis is a dermatosis that requires the evaluation of the number of melanocytes as a fundamental diagnostic clue (eg, postinflammatory hypopigmentation), the biopsy will probably not be useful. On the other hand, when our differential diagnosis has characteristic diagnostic findings independent of the number of melanocytes or the presence of melanin, the biopsy will be useful (eg, hypopigmented mycosis fungoides).

Thus, we can understand why the histologic differentiation between vitiligo, pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation is difficult. The histology images of these 4 diseases may show different degrees of melanocyte and melanin decrease, spongiosis, and in the superficial dermis melanophages and mononuclear inflammatory infiltrate.⁷

Nevus depigmentosus also may generate diagnostic confusion with vitiligo. Although it is unilateral and usually congenital, it can appear as late as 3 years of age, leading to an initial clinical differential diagnosis of vitiligo. The histologic findings in this nevus also overlap with vitiligo. The characteristic findings are presence of melanocytes and decreased pigment in the keratinocytes compared with perilesional skin. Therefore, a biopsy is not a solution to this diagnostic dilemma.⁸

In all the differentials named, the solution to the diagnostic doubt is not based on the histologic findings but on the clinical evolution of the patients. In cases of vitiligo, the lesions will become more evident in the evolution. They will eventually disappear in pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation and will remain unchanged in nevus depigmentosus. It is important, especially when we are dealing with concerned parents/guardians, to convey the importance of assessing the evolution of the disease as the main diagnostic procedure. Even though a biopsy is minimally invasive, it is usually stressful on children, it may leave sequelae, and above all it will not contribute to the diagnosis in this clinical context.

There are other clinical circumstances in the scenario of hypochromic or achromic lesions in which the biopsy will be useful: If we consider an initial genital lichen sclerosus vs vitiligo. In lichen sclerosus the biopsy will show dermal hyalinosis and interphase changes; absence of both will support vitiligo. If we need to differentiate hypopigmented mycosis fungoides from vitiligo, we will find an infiltrate of pleomorphic lymphocytes in the epidermis and dermis in the former and an absence of these findings in vitiligo. Finally, if we find granulomas in a biopsy of an achromic or hypopigmented lesion, we may be dealing with hypopigmented sarcoidosis or Hansen disease.

It also is important to choose the best site to perform the biopsy to have the best chance at diagnosing vitiligo histologically. As already described, in the edges and in the perilesional skin we can find remnant melanocytes, Langerhans cells, and interphase changes that do not allow us to clearly evaluate the main change that is the loss of melanocytes and melanin. In fact, a biopsy of the edge of a vitiligo macula can lead to confusion. For example, if the differential diagnosis is lichen sclerosus and the image we see in the biopsy of the edge of a vitiligo lesion is an interface reaction, we can interpret it as a finding that favors lichen sclerosus. In this way, it is better to biopsy the center of a well-constituted vitiligo lesion where we have the best chance to assess the absence of melanin and melanocytes.

The vitiligo differential diagnosis can be divided into 2 groups: entities that are difficult to differentiate from vitiligo histologically (ie, pityriasis alba, postinflammatory hypopigmentation, progressive macular hypopigmentation, nevus depigmentosus) and entities that are easily distinguishable from vitiligo histologically (ie, lichen sclerosus, mycosis fungoides, sarcoidosis, leprosy). If our differential diagnosis was found in the first group, the final diagnosis should be based on the evolution of the patient. If it was in the second group, a biopsy of the center of the lesion will be useful and may allow us to reach a definitive diagnosis.

The histopathologic diagnosis of vitiligo is classically understood as the absence of melanocytes and melanin in the skin biopsy.¹ It is difficult for a pathologist to establish the absolute absence of melanocytes and melanin in a skin biopsy. Therefore, we need to take into consideration many variables when we face the possibility to biopsy a vitiligo lesion.

The basis of the clinical diagnosis of vitiligo is the appearance of achromic lesions in periorificial and acral areas; however, sometimes it is difficult to differentiate between an achromic or hypochromic lesion. Although Wood light is of great help in these circumstances, it still can be difficult to make the diagnosis with certainty.

In other cases, the lesions do not present a classic distribution of vitiligo, and other differential diagnoses are considered. For example, if we see a single hypochromic or achromic lesion in a young child, then the main differential diagnosis would be achromic nevus. If there are multiple lesions, then we may consider progressive macular hypomelanosis, postinflammatory hypopigmentation, and hypopigmented mycosis fungoides. In genital lesions, the differential diagnosis between initial lichen sclerosus and vitiligo also can be considered. Finally, we must always bear in mind that both sarcoidosis and Hansen disease can appear as achromic or hypochromic lesions.

The histologic diagnosis of vitiligo in a completely constituted lesion implies the total loss of melanocytes and melanin in the epidermis. Additional histologic findings are described at the edge of the advanced border, such as the presence of melanocytes that have increased in size with large dendrites and lymphoid infiltrate. In perilesional skin, vacuolated keratinocytes and Langerhans cells have increased in number and repositioned in the basal layer, with visible degeneration of nerves and sweat glands. Lymphocytes also can be found in contact with the melanocytes.² It is important to note that in addition to these histologic findings, it is common to find spongiosis, mononuclear superficial perivascular inflammatory infiltrate, and melanophages in biopsies of vitiligo.³

Given that ensuring the absence of melanocytes is central to diagnosis and melanocytes can be difficult to identify or differentiate from repositioned Langerhans cells in the basal layer with hematoxylin and eosin stain, immunohistochemical techniques must be performed every time we are dealing with vitiligo biopsies. Although there are no studies comparing the diagnostic value of the different immunohistochemical techniques in vitiligo, dihydroxyphenylalanine (DOPA) seems to be a good option, as it will only mark active melanocytes. Human melanoma black 45 (HMB-45), anti-TYRP1 (Mel-5), and antimelanoma gp 100 antibody (NKI/beteb) also have been used. Some authors recommend the use of pan melanoma because it includes 3 markers—HMB-45, tyrosinase, and Mart-1. Currently, SRY-related HMG-box10 (SOX10) seems to be a good option, as it is a nuclear marker that makes it easier to differentiate melanocytes from pigmented keratinocytes.⁴

Establishing a complete absence of melanocytes in the lesions or finding there are melanocytes but they are inactivated is key to evaluating the pathogenesis of vitiligo and directly affects the histologic diagnosis and eventually even the treatment. Le Poole et al⁵ used a panel of 17 monoclonal antibodies and a polyclonal antibody in lesions of 12 patients with vitiligo without identifying the presence of melanocytes. They concluded that there are no melanocytes in lesions of vitiligo.⁵

In a subsequent study with a larger number of patients, Kim et al² found melanocytes that marked with NKI/beteb and Mart-1 in 12 of 100 patients with vitiligo. They also showed melanocytes by electron microscopy in lesional skin of 1 of 3 patients with vitiligo.² Tobin et al⁶ managed to grow melanocytes from skin with vitiligo and confirmed the presence of melanin in basal keratinocytes of lesions of stable vitiligo. From this evidence we can conclude that the absence of melanocytes and melanin in the epidermis confirms the diagnosis of vitiligo; however, the opposite is not true—that is, the presence of melanocytes or melanin in a skin biopsy does not rule out the diagnosis of vitiligo.

Taking this information into consideration, we can understand that if our differential diagnosis is a dermatosis that requires the evaluation of the number of melanocytes as a fundamental diagnostic clue (eg, postinflammatory hypopigmentation), the biopsy will probably not be useful. On the other hand, when our differential diagnosis has characteristic diagnostic findings independent of the number of melanocytes or the presence of melanin, the biopsy will be useful (eg, hypopigmented mycosis fungoides).

Thus, we can understand why the histologic differentiation between vitiligo, pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation is difficult. The histology images of these 4 diseases may show different degrees of melanocyte and melanin decrease, spongiosis, and in the superficial dermis melanophages and mononuclear inflammatory infiltrate.⁷

Nevus depigmentosus also may generate diagnostic confusion with vitiligo. Although it is unilateral and usually congenital, it can appear as late as 3 years of age, leading to an initial clinical differential diagnosis of vitiligo. The histologic findings in this nevus also overlap with vitiligo. The characteristic findings are presence of melanocytes and decreased pigment in the keratinocytes compared with perilesional skin. Therefore, a biopsy is not a solution to this diagnostic dilemma.⁸

In all the differentials named, the solution to the diagnostic doubt is not based on the histologic findings but on the clinical evolution of the patients. In cases of vitiligo, the lesions will become more evident in the evolution. They will eventually disappear in pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation and will remain unchanged in nevus depigmentosus. It is important, especially when we are dealing with concerned parents/guardians, to convey the importance of assessing the evolution of the disease as the main diagnostic procedure. Even though a biopsy is minimally invasive, it is usually stressful on children, it may leave sequelae, and above all it will not contribute to the diagnosis in this clinical context.

There are other clinical circumstances in the scenario of hypochromic or achromic lesions in which the biopsy will be useful: If we consider an initial genital lichen sclerosus vs vitiligo. In lichen sclerosus the biopsy will show dermal hyalinosis and interphase changes; absence of both will support vitiligo. If we need to differentiate hypopigmented mycosis fungoides from vitiligo, we will find an infiltrate of pleomorphic lymphocytes in the epidermis and dermis in the former and an absence of these findings in vitiligo. Finally, if we find granulomas in a biopsy of an achromic or hypopigmented lesion, we may be dealing with hypopigmented sarcoidosis or Hansen disease.

It also is important to choose the best site to perform the biopsy to have the best chance at diagnosing vitiligo histologically. As already described, in the edges and in the perilesional skin we can find remnant melanocytes, Langerhans cells, and interphase changes that do not allow us to clearly evaluate the main change that is the loss of melanocytes and melanin. In fact, a biopsy of the edge of a vitiligo macula can lead to confusion. For example, if the differential diagnosis is lichen sclerosus and the image we see in the biopsy of the edge of a vitiligo lesion is an interface reaction, we can interpret it as a finding that favors lichen sclerosus. In this way, it is better to biopsy the center of a well-constituted vitiligo lesion where we have the best chance to assess the absence of melanin and melanocytes.

The vitiligo differential diagnosis can be divided into 2 groups: entities that are difficult to differentiate from vitiligo histologically (ie, pityriasis alba, postinflammatory hypopigmentation, progressive macular hypopigmentation, nevus depigmentosus) and entities that are easily distinguishable from vitiligo histologically (ie, lichen sclerosus, mycosis fungoides, sarcoidosis, leprosy). If our differential diagnosis was found in the first group, the final diagnosis should be based on the evolution of the patient. If it was in the second group, a biopsy of the center of the lesion will be useful and may allow us to reach a definitive diagnosis.

LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.

Bruce Jancin/MDedge News

Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.

PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.

“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.

Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.

There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).

 

‘Hemangiomas – but we were taught that they go away’

Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).

Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.

“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.

The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.

“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.

The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.

“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”

Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.

Bruce Jancin/MDedge News

Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.

PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.

“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.

Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.

There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).

 

‘Hemangiomas – but we were taught that they go away’

Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).

Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.

“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.

The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.

“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.

The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.

“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”

Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Reassuring evidence of the safety of oral propranolol for treatment of complicated infantile hemangiomas in patients with PHACE syndrome comes from a recent multicenter study.

Bruce Jancin/MDedge News

Oral propranolol is now well-ensconced as first-line therapy for complicated infantile hemangiomas in otherwise healthy children. However, the beta-blocker’s use in PHACE (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, and Eye abnormalities) syndrome has been controversial, with concerns raised by some that it might raise the risk for arterial ischemic stroke. Not so, Moise L. Levy, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“I’m not suggesting you use propranolol with reckless abandon in this population, but this stroke concern is something that should be put to bed based on this study,” advised Dr. Levy, professor of dermatology and pediatrics at Dell Medical School in Austin, Tex., and physician-in-chief at Dell Children’s Medical Center.

PHACE syndrome is characterized by large, thick, plaque-like hemangiomas greater than 5 cm in size, most commonly on the face, although they can be located elsewhere.

“There was concern that if you found severely altered cerebrovascular arterial flow and you put a kid on a beta-blocker you might be causing some harm. But what I will tell you is that in this recently published paper this was not in fact an issue,” he said.

Dr. Levy was not an investigator in the multicenter retrospective study, which included 76 patients with PHACE syndrome treated for infantile hemangioma with oral propranolol at 0.3 mg/kg per dose or more at 11 academic tertiary care pediatric dermatology clinics. Treatment started at a median age of 56 days.

There were no strokes, TIAs, cardiovascular events, or other significant problems associated with treatment. Twenty-nine children experienced mild adverse events: minor gastrointestinal or respiratory symptoms, and sleep disturbances were threefold more frequent than reported with placebo in another study. The investigators noted that the safety experience in their PHACE syndrome population compared favorably with that in 726 infants without PHACE syndrome who received oral propranolol for hemangiomas, where the incidence of serious adverse events on treatment was 0.4% (JAMA Dermatol. 2019 Dec 11. doi: 10.1001/jamadermatol.2019.3839).

 

‘Hemangiomas – but we were taught that they go away’

Dr. Levy gave a shout-out to the American Academy of Pediatrics for publishing interdisciplinary expert consensus-based practice guidelines for the management of infantile hemangiomas, which he praised as “quite well done” (Pediatrics. 2019 Jan;143[1]. pii: e20183475. doi: 10.1542/peds.2018-3475).

Following release of the guidelines last year, he and other pediatric vascular anomalies experts saw an uptick in referrals from general pediatricians, which has since tapered off.

“It’s probably like for all of us: We read an article, it’s fresh on the mind, then you forget about the article and what you’ve read. So we need a little reinforcement from a learning perspective. This is a great article,” he said.

The guidelines debunk as myth the classic teaching that infantile hemangiomas go away. Explicit information is provided about the high-risk anatomic sites warranting consideration for early referral, including the periocular, lumbosacral, and perineal areas, the lip, and lower face.

“The major point is early identification of those lesions requiring evaluation and intervention. Hemangiomas generally speaking are at their ultimate size by 3-5 months of age. The bottom line is if you think something needs to be done, please send that patient, or act upon that patient, sooner rather than later. I can’t tell you how many cases of hemangiomas I’ve seen when the kid is 18 months of age, 3 years of age, 5 years, with a large area of redundant skin, scarring, or something of that sort, and it would have been really nice to have seen them earlier and acted upon them then,” the pediatric dermatologist said.

The guidelines recommend intervention or referral by 1 month of age, ideally. Guidance is provided about the use of oral propranolol as first-line therapy.

“Propranolol is something that has been a real game changer for us,” he noted. “Many people continue to be worried about side effects in using this, particularly in the young childhood population, but this paper shows pretty clearly that hypotension or bradycardia is not a real concern. I never hospitalize these patients for propranolol therapy except in high-risk populations: very preemie, any history of breathing problems. We check the blood pressure and heart rate at baseline, again at 7-10 days, and at every visit. We’ve never found any significant drop in blood pressure.”

Dr. Levy reported financial relationships with half a dozen pharmaceutical companies, none relevant to his presentation.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com