Pigmentation Disorders

To the Editor:

Acanthosis nigricans (AN) is characterized by asymptomatic, hyperpigmented, velvety plaques that can occur anywhere on the body but most often present on the skin of the neck, axillae, groin, and other body folds.^1-12 Although there are 5 subtypes, benign AN is the most common and is related to insulin resistance.^1-4 Insulin can bind to insulinlike growth factor 1 (IGF-1) on keratinocytes, stimulating their proliferation. In type 2 diabetes mellitus, endogenous insulin levels are high enough to bind IGF-1 and activate keratinocytes, leading to the development of AN. Insulin injections have been associated with cutaneous side effects including lipoatrophy, lipohypertrophy, and postinflammatory hyperpigmentation.³ Acanthosis nigricans at insulin injection sites is a rare clinical condition.

A 64-year-old man presented for evaluation of a growing asymptomatic lesion on the abdomen of 6 years’ duration. He had a 17-year history of type 2 diabetes mellitus treated with insulin injections for 14 years after failing oral hypoglycemic agents. The patient reported injecting at the same site on the abdomen for the last 14 years. Physical examination revealed a lichenified, hyperpigmented, verrucous plaque on the lower abdomen under the umbilicus (Figure 1). No similar skin lesions were observed elsewhere on the body. A punch biopsy of the plaque showed hyperkeratosis, papillomatosis, acanthosis, and hyperpigmentation, which was consistent with AN (Figure 2). The patient was instructed to rotate injection sites and avoid the affected area. Over-the-counter ammonium lactate cream applied twice daily to the affected site also was recommended. After 2 months of treatment with this regimen, the patient reported softening and lightening of the lesion on the abdomen.

A PubMed search of articles indexed for MEDLINE for all English-language studies with human participants using the terms acanthosis nigricans and insulin injections yielded 20 results. Of them, 13 discussed localized AN at insulin injection sites: 12 case reports (Table)^1-12 and 1 observational study in a group of diabetic patients.¹³

It has been suggested that localized AN at insulin injection sites develops through similar mechanisms as benign AN. Contributing factors to the development of benign AN may be IGF-1, fibroblast growth factor, and epidermal growth factor.^1-3 Insulin is similar in structure to IGF-1 and can bind to IGF-1 receptors at high enough concentrations. Insulinlike growth factor 1 receptors are present on keratinocytes and fibroblasts, which proliferate upon activation, leading to the development of AN.^1-3 Localized AN is thought to occur when repetitive insulin at the injection site saturates IGF-1 receptors on local keratinocytes.

Based on our patient and prior reports in the literature, localized AN is an uncommon cutaneous complication of insulin injections. Physicians should ask about repetitive insulin injections in the same site when localized AN occurs in patients with diabetes mellitus on insulin therapy. They also should discuss the importance of rotating sites for insulin adminstration to prevent the development of cutaneous complications including AN.

To the Editor:

Acanthosis nigricans (AN) is characterized by asymptomatic, hyperpigmented, velvety plaques that can occur anywhere on the body but most often present on the skin of the neck, axillae, groin, and other body folds.^1-12 Although there are 5 subtypes, benign AN is the most common and is related to insulin resistance.^1-4 Insulin can bind to insulinlike growth factor 1 (IGF-1) on keratinocytes, stimulating their proliferation. In type 2 diabetes mellitus, endogenous insulin levels are high enough to bind IGF-1 and activate keratinocytes, leading to the development of AN. Insulin injections have been associated with cutaneous side effects including lipoatrophy, lipohypertrophy, and postinflammatory hyperpigmentation.³ Acanthosis nigricans at insulin injection sites is a rare clinical condition.

A 64-year-old man presented for evaluation of a growing asymptomatic lesion on the abdomen of 6 years’ duration. He had a 17-year history of type 2 diabetes mellitus treated with insulin injections for 14 years after failing oral hypoglycemic agents. The patient reported injecting at the same site on the abdomen for the last 14 years. Physical examination revealed a lichenified, hyperpigmented, verrucous plaque on the lower abdomen under the umbilicus (Figure 1). No similar skin lesions were observed elsewhere on the body. A punch biopsy of the plaque showed hyperkeratosis, papillomatosis, acanthosis, and hyperpigmentation, which was consistent with AN (Figure 2). The patient was instructed to rotate injection sites and avoid the affected area. Over-the-counter ammonium lactate cream applied twice daily to the affected site also was recommended. After 2 months of treatment with this regimen, the patient reported softening and lightening of the lesion on the abdomen.

A PubMed search of articles indexed for MEDLINE for all English-language studies with human participants using the terms acanthosis nigricans and insulin injections yielded 20 results. Of them, 13 discussed localized AN at insulin injection sites: 12 case reports (Table)^1-12 and 1 observational study in a group of diabetic patients.¹³

It has been suggested that localized AN at insulin injection sites develops through similar mechanisms as benign AN. Contributing factors to the development of benign AN may be IGF-1, fibroblast growth factor, and epidermal growth factor.^1-3 Insulin is similar in structure to IGF-1 and can bind to IGF-1 receptors at high enough concentrations. Insulinlike growth factor 1 receptors are present on keratinocytes and fibroblasts, which proliferate upon activation, leading to the development of AN.^1-3 Localized AN is thought to occur when repetitive insulin at the injection site saturates IGF-1 receptors on local keratinocytes.

Based on our patient and prior reports in the literature, localized AN is an uncommon cutaneous complication of insulin injections. Physicians should ask about repetitive insulin injections in the same site when localized AN occurs in patients with diabetes mellitus on insulin therapy. They also should discuss the importance of rotating sites for insulin adminstration to prevent the development of cutaneous complications including AN.

To the Editor:

Acanthosis nigricans (AN) is characterized by asymptomatic, hyperpigmented, velvety plaques that can occur anywhere on the body but most often present on the skin of the neck, axillae, groin, and other body folds.^1-12 Although there are 5 subtypes, benign AN is the most common and is related to insulin resistance.^1-4 Insulin can bind to insulinlike growth factor 1 (IGF-1) on keratinocytes, stimulating their proliferation. In type 2 diabetes mellitus, endogenous insulin levels are high enough to bind IGF-1 and activate keratinocytes, leading to the development of AN. Insulin injections have been associated with cutaneous side effects including lipoatrophy, lipohypertrophy, and postinflammatory hyperpigmentation.³ Acanthosis nigricans at insulin injection sites is a rare clinical condition.

A 64-year-old man presented for evaluation of a growing asymptomatic lesion on the abdomen of 6 years’ duration. He had a 17-year history of type 2 diabetes mellitus treated with insulin injections for 14 years after failing oral hypoglycemic agents. The patient reported injecting at the same site on the abdomen for the last 14 years. Physical examination revealed a lichenified, hyperpigmented, verrucous plaque on the lower abdomen under the umbilicus (Figure 1). No similar skin lesions were observed elsewhere on the body. A punch biopsy of the plaque showed hyperkeratosis, papillomatosis, acanthosis, and hyperpigmentation, which was consistent with AN (Figure 2). The patient was instructed to rotate injection sites and avoid the affected area. Over-the-counter ammonium lactate cream applied twice daily to the affected site also was recommended. After 2 months of treatment with this regimen, the patient reported softening and lightening of the lesion on the abdomen.

A PubMed search of articles indexed for MEDLINE for all English-language studies with human participants using the terms acanthosis nigricans and insulin injections yielded 20 results. Of them, 13 discussed localized AN at insulin injection sites: 12 case reports (Table)^1-12 and 1 observational study in a group of diabetic patients.¹³

It has been suggested that localized AN at insulin injection sites develops through similar mechanisms as benign AN. Contributing factors to the development of benign AN may be IGF-1, fibroblast growth factor, and epidermal growth factor.^1-3 Insulin is similar in structure to IGF-1 and can bind to IGF-1 receptors at high enough concentrations. Insulinlike growth factor 1 receptors are present on keratinocytes and fibroblasts, which proliferate upon activation, leading to the development of AN.^1-3 Localized AN is thought to occur when repetitive insulin at the injection site saturates IGF-1 receptors on local keratinocytes.

Based on our patient and prior reports in the literature, localized AN is an uncommon cutaneous complication of insulin injections. Physicians should ask about repetitive insulin injections in the same site when localized AN occurs in patients with diabetes mellitus on insulin therapy. They also should discuss the importance of rotating sites for insulin adminstration to prevent the development of cutaneous complications including AN.

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

The Diagnosis: Incontinentia Pigmenti 

The patient was diagnosed clinically with the vesicular stage of incontinentia pigmenti (IP), a rare, X-linked dominant neuroectodermal dysplasia that usually is lethal in males. The genetic mutation has been identified in the IKBKG gene (inhibitor of nuclear factor κB; formally NEMO), which leads to a truncated and defective nuclear factor κB. Female infants survive and display characteristic findings on examination due to X-inactivation leading to mosaicism.¹ Worldwide, there are approximately 27.6 new cases of IP per year. Although it is heritable, the majority (65%-75%) of cases are due to sporadic mutations, with the remaining minority (25%-35%) representing familial disease.¹ 

Cutaneous findings of IP classically progress through 4 stages, though individual patients often do not develop the characteristic lesions of each of the 4 stages. The vesicular stage (stage 1) presented in our patient (quiz image). This stage presents within 2 weeks of birth in 90% of patients and typically disappears when the patient is approximately 4 months of age.^1-3 Although the clinical presentation is striking, it is essential to rule out herpes simplex virus infection, which can mimic vesicular IP. Localized herpes simplex virus is most commonly seen in clusters on the scalp and often is not present at birth. Alternatively, IP is most often seen on the extremities in bands or whorls of distribution along Blaschko lines,⁴ as in this patient. 

Stage 2 (the verrucous stage) presents with verrucous papules or pustules in a similar blaschkoid distribution. Areas previously involved in stage 1 are not always the same areas affected in stage 2. Approximately 70% of patients develop stage 2 lesions, usually at 2 to 6 weeks of age.^1-3 Erythema toxicum neonatorum presents in the first week of life with pustules often on the trunk or extremities, but these lesions are not confined to Blaschko lines, differentiating it from IP.⁴ 

The third stage (hyperpigmented stage) lends the disease its name and occurs in 90% to 95% of patients with IP. Linear and whorled hyperpigmentation develops in early infancy and can either persist or fade by adolescence.¹ Pustules and hyperpigmentation in transient neonatal pustular melanosis may be similar to this stage of IP, but the distribution is more variable and progression to other lesions is not seen.⁵ 

The fourth and final stage is the hypopigmented stage, whereby blaschkoid linear and whorled lines of hypopigmentation with or without both atrophy and alopecia develop in 75% of patients. This is the last finding, beginning in adolescence and often persisting into adulthood.¹ Goltz syndrome is another X-linked dominant disorder with features similar to IP. Verrucous and atrophic lesions along Blaschko lines are reminiscent of the second and fourth stages of IP but are differentiated in Goltz syndrome because they present concurrently rather than in sequential stages such as IP. Similar extracutaneous organs are affected such as the eyes, teeth, and nails; however, Goltz syndrome may be associated with more distinguishing systemic signs such as sweating and skeletal abnormalities.⁶ 

Given its unique appearance, physicians usually diagnose IP clinically after identification of characteristic linear lesions along the lines of Blaschko in an infant or neonate. Skin biopsy is confirmatory, which would differ depending on the stage of disease biopsied. The vesicular stage is characterized by eosinophilic spongiosis and is differentiated from other items on the histologic differential diagnosis by the presence of dyskeratosis.⁷ Genetic testing is available and should be performed along with a physical examination of the mother for counseling  purposes.¹ 

Proper diagnosis is critical because of the potential multisystem nature of the disease with implications for longitudinal care and prognosis in patients. As in other neurocutaneous disease, IP can affect the hair, nails, teeth, central nervous system, and eyes. All IP patients receive a referral to ophthalmology at the time of diagnosis for a dilated fundus examination, with repeat examinations every several months initially--every 3 months for a year, every 6 months from 1 to 3 years of age--and annually thereafter. Dental evaluation should occur at 6 months of age or whenever the first tooth erupts.¹ Mental retardation, seizures, and developmental delay can occur and usually are evident in the first year of life. Patients should have developmental milestones closely  monitored and be referred to appropriate specialists if signs or symptoms develop consistent with neurologic involvement.¹ 

LAHAINA, HAWAII – Individuals with vitiligo demonstrated a markedly reduced rate of internal malignancies in a recent first-of-its-kind “big data” study from South Korea, Iltefat Hamzavi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Previous studies by Dr. Hamzavi and others have established that vitiligo patients have a reduced risk of melanoma and perhaps nonmelanoma skin cancers as well. But the South Korean national study of 101,078 vitiligo patients matched by age and sex to twice as many vitiligo-free controls was the first large examination of the association between vitiligo and internal malignancies. The findings suggest that immunosurveillance in patients with the disease is not merely a skin-deep phenomenon, noted Dr. Hamzavi, of the MultiCultural Dermatology Center at Henry Ford Hospital in Detroit.

“Vitiligo is probably a systemic disease in which there may be increased immunosurveillance. The point here is that as we suppress the disease, we have to be careful that we’re not going to increase cancer rates,” the dermatologist explained in an interview. “This is big data, and something to be aware of, but don’t act on it yet in clinical practice. I just want people to be aware that all of these autoimmune diseases are there for a reason. There are lower rates of melanoma and internal cancers in patients who have vitiligo, but what that means for our new therapies that are coming up we don’t know yet.”

He predicted that the study will open up an active new research domain, but it will take time to find definitive answers as to whether emerging immunomodulatory therapies for patients with vitiligo might, in some instances, increase their current favorably lower risk of internal malignancies. In the meantime, physicians interested in treating vitiligo off label with, for example, Janus kinase (JAK) inhibitors will want to be particularly cautious in patients with a strong history of skin cancer or internal malignancies.

The retrospective, population-based study utilized data from the Korean National Health Insurance claims database. The investigators found that the incidence rate of internal malignancies was 612.9 per 100,000 person-years in the vitiligo group and 708.9 per 100,000 person-years in controls, for a statistically significant and clinically meaningful 14% relative risk reduction after adjustment for age, sex, and comorbid conditions.

Among the most striking organ-specific findings: the vitiligo group had a 38% relative risk reduction in colorectal cancer, a 25% reduction in the risk of lung cancer, and a 38% decrease in ovarian cancer. In contrast, they had a 20% increase in the risk of thyroid cancer (J Clin Oncol. 2019 Apr 10;37[11]:903-11).

Despite the fact that vitiligo is a common disease that affects 0.5%-1% of the population worldwide, for decades it has been something of a pharmacotherapeutic backwater. That’s changed recently and in dramatic fashion as a result of new understanding of the disease pathogenesis. The JAK inhibitors are now under active investigation for the treatment of vitiligo. Indeed, ruxolitinib cream, a potent JAK-1 and -2 inhibitor, is now in phase 3 investigation following a highly successful phase 2 trial. Interleukin-15 blockade is another promising avenue.

Dr. Hamzavi reported serving as a consultant to AbbVie, Aclaris, Novartis, and Pfizer, and receiving research funding from Estee Lauder, Clinuvel Pharmaceuticals, Incyte, and Pfizer. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Individuals with vitiligo demonstrated a markedly reduced rate of internal malignancies in a recent first-of-its-kind “big data” study from South Korea, Iltefat Hamzavi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Previous studies by Dr. Hamzavi and others have established that vitiligo patients have a reduced risk of melanoma and perhaps nonmelanoma skin cancers as well. But the South Korean national study of 101,078 vitiligo patients matched by age and sex to twice as many vitiligo-free controls was the first large examination of the association between vitiligo and internal malignancies. The findings suggest that immunosurveillance in patients with the disease is not merely a skin-deep phenomenon, noted Dr. Hamzavi, of the MultiCultural Dermatology Center at Henry Ford Hospital in Detroit.

“Vitiligo is probably a systemic disease in which there may be increased immunosurveillance. The point here is that as we suppress the disease, we have to be careful that we’re not going to increase cancer rates,” the dermatologist explained in an interview. “This is big data, and something to be aware of, but don’t act on it yet in clinical practice. I just want people to be aware that all of these autoimmune diseases are there for a reason. There are lower rates of melanoma and internal cancers in patients who have vitiligo, but what that means for our new therapies that are coming up we don’t know yet.”

He predicted that the study will open up an active new research domain, but it will take time to find definitive answers as to whether emerging immunomodulatory therapies for patients with vitiligo might, in some instances, increase their current favorably lower risk of internal malignancies. In the meantime, physicians interested in treating vitiligo off label with, for example, Janus kinase (JAK) inhibitors will want to be particularly cautious in patients with a strong history of skin cancer or internal malignancies.

The retrospective, population-based study utilized data from the Korean National Health Insurance claims database. The investigators found that the incidence rate of internal malignancies was 612.9 per 100,000 person-years in the vitiligo group and 708.9 per 100,000 person-years in controls, for a statistically significant and clinically meaningful 14% relative risk reduction after adjustment for age, sex, and comorbid conditions.

Among the most striking organ-specific findings: the vitiligo group had a 38% relative risk reduction in colorectal cancer, a 25% reduction in the risk of lung cancer, and a 38% decrease in ovarian cancer. In contrast, they had a 20% increase in the risk of thyroid cancer (J Clin Oncol. 2019 Apr 10;37[11]:903-11).

Despite the fact that vitiligo is a common disease that affects 0.5%-1% of the population worldwide, for decades it has been something of a pharmacotherapeutic backwater. That’s changed recently and in dramatic fashion as a result of new understanding of the disease pathogenesis. The JAK inhibitors are now under active investigation for the treatment of vitiligo. Indeed, ruxolitinib cream, a potent JAK-1 and -2 inhibitor, is now in phase 3 investigation following a highly successful phase 2 trial. Interleukin-15 blockade is another promising avenue.

Dr. Hamzavi reported serving as a consultant to AbbVie, Aclaris, Novartis, and Pfizer, and receiving research funding from Estee Lauder, Clinuvel Pharmaceuticals, Incyte, and Pfizer. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

LAHAINA, HAWAII – Individuals with vitiligo demonstrated a markedly reduced rate of internal malignancies in a recent first-of-its-kind “big data” study from South Korea, Iltefat Hamzavi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/MDedge News

Previous studies by Dr. Hamzavi and others have established that vitiligo patients have a reduced risk of melanoma and perhaps nonmelanoma skin cancers as well. But the South Korean national study of 101,078 vitiligo patients matched by age and sex to twice as many vitiligo-free controls was the first large examination of the association between vitiligo and internal malignancies. The findings suggest that immunosurveillance in patients with the disease is not merely a skin-deep phenomenon, noted Dr. Hamzavi, of the MultiCultural Dermatology Center at Henry Ford Hospital in Detroit.

“Vitiligo is probably a systemic disease in which there may be increased immunosurveillance. The point here is that as we suppress the disease, we have to be careful that we’re not going to increase cancer rates,” the dermatologist explained in an interview. “This is big data, and something to be aware of, but don’t act on it yet in clinical practice. I just want people to be aware that all of these autoimmune diseases are there for a reason. There are lower rates of melanoma and internal cancers in patients who have vitiligo, but what that means for our new therapies that are coming up we don’t know yet.”

He predicted that the study will open up an active new research domain, but it will take time to find definitive answers as to whether emerging immunomodulatory therapies for patients with vitiligo might, in some instances, increase their current favorably lower risk of internal malignancies. In the meantime, physicians interested in treating vitiligo off label with, for example, Janus kinase (JAK) inhibitors will want to be particularly cautious in patients with a strong history of skin cancer or internal malignancies.

The retrospective, population-based study utilized data from the Korean National Health Insurance claims database. The investigators found that the incidence rate of internal malignancies was 612.9 per 100,000 person-years in the vitiligo group and 708.9 per 100,000 person-years in controls, for a statistically significant and clinically meaningful 14% relative risk reduction after adjustment for age, sex, and comorbid conditions.

Among the most striking organ-specific findings: the vitiligo group had a 38% relative risk reduction in colorectal cancer, a 25% reduction in the risk of lung cancer, and a 38% decrease in ovarian cancer. In contrast, they had a 20% increase in the risk of thyroid cancer (J Clin Oncol. 2019 Apr 10;37[11]:903-11).

Despite the fact that vitiligo is a common disease that affects 0.5%-1% of the population worldwide, for decades it has been something of a pharmacotherapeutic backwater. That’s changed recently and in dramatic fashion as a result of new understanding of the disease pathogenesis. The JAK inhibitors are now under active investigation for the treatment of vitiligo. Indeed, ruxolitinib cream, a potent JAK-1 and -2 inhibitor, is now in phase 3 investigation following a highly successful phase 2 trial. Interleukin-15 blockade is another promising avenue.

Dr. Hamzavi reported serving as a consultant to AbbVie, Aclaris, Novartis, and Pfizer, and receiving research funding from Estee Lauder, Clinuvel Pharmaceuticals, Incyte, and Pfizer. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

bjancin@mdedge.com

Fitzpatrick skin type (FST) is the most commonly used classification system in dermatologic practice. It was developed by Thomas B. Fitzpatrick, MD, PhD, in 1975 to assess the propensity of the skin to burn during phototherapy.¹ Fitzpatrick skin type also can be used to assess the clinical benefits and efficacy of cosmetic procedures, including laser hair removal, chemical peel and dermabrasion, tattoo removal, spray tanning, and laser resurfacing for acne scarring.² The original FST classifications included skin types I through IV; skin types V and VI were later added to include individuals of Asian, Indian, and African origin.¹ As a result, FST often is used by providers as a means of describing constitutive skin color and ethnicity.³

How did FST transition from describing the propensity of the skin to burn from UV light exposure to categorizing skin color, thereby becoming a proxy for race? It most likely occurred because there has not been another widely adopted classification system for describing skin color that can be applied to all skin types. Even when the FST classification scale is used as intended, there are inconsistencies with its accuracy; for example, self-reported FSTs have correlated poorly with sunburn risk as well as physician-reported FSTs.^4,5 Although physician-reported FSTs have been demonstrated to correlate with race, race does not consistently correlate with objective measures of pigmentation or self-reported FSTs.⁵ For example, Japanese women often self-identify as FST type II, but Asian skin generally is considered to be nonwhite.¹ Fitzpatrick himself acknowledged that race and ethnicity are cultural and political terms with no scientific basis.⁶ Fitzpatrick skin type also has been demonstrated to correlate poorly with constitutive skin color and minimal erythema dose values.⁷

We conducted an anonymous survey of dermatologists and dermatology trainees to evaluate how providers use FST in their clinical practice as well as how it is used to describe race and ethnicity.

Methods

The survey was distributed electronically to dermatologists and dermatology trainees from March 13 to March 28, 2019, using the Association of Professors of Dermatology listserv, as well as in person at the annual Skin of Color Society meeting in Washington, DC, on February 28, 2019. The 8-item survey included questions about physician demographics (ie, primary practice setting, board certification, and geographic location); whether the respondent identified as an individual with skin of color; and how the respondent utilized FST in clinical notes (ie, describing race/ethnicity, skin cancer risk, and constitutive [baseline] skin color; determining initial phototherapy dosage and suitability for laser treatments, and likelihood of skin burning). A t test was used to determine whether dermatologists who identified as having skin of color utilized FST differently.

Results

A total of 141 surveys were returned, and 140 respondents were included in the final analysis. Given the methods used to distribute the survey, a response rate could not be calculated. The respondents included more board-certified dermatologists (70%) than dermatology trainees (30%). Ninety-three percent of respondents indicated an academic institution as their primary practice location. Notably, 26% of respondents self-identified as having skin of color.

Forty-one percent of all respondents agreed that FST should be included in their clinical documentation. In response to the question “In what scenarios would you refer to FST in a clinical note?” 31% said they used FST to describe patients’ race or ethnicity, 47% used it to describe patients’ constitutive skin color, and 22% utilized it in both scenarios. Respondents who did not identify as having skin of color were more likely to use FST to describe constitutive skin color, though this finding was not statistically significant (P=.063). Anecdotally, providers also included FST in clinical notes on postinflammatory hyperpigmentation, melasma, and treatment with cryotherapy.

Comment

The US Census Bureau has estimated that half of the US population will be of non-European descent by 2050.⁸ As racial and ethnic distinctions continue to be blurred, attempts to include all nonwhite skin types under the umbrella term skin of color becomes increasingly problematic. The true number of skin colors is unknown but likely is infinite, as Brazilian artist Angélica Dass has demonstrated with her photographic project “Humanae” (Figure). Given this shift in demographics and the limitations of the FST, alternative methods of describing skin color must be developed.

The results of our survey suggest that approximately one-third to half of academic dermatologists/dermatology trainees use FST to describe race/ethnicity and/or constitutive skin color. This misuse of FST may occur more frequently among physicians who do not identify as having skin of color. Additionally, misuse of FST in academic settings may be problematic and confusing for medical students who may learn to use this common dermatologic tool outside of its original intent.

We acknowledge that the conundrum of how to classify individuals with nonwhite skin or skin of color is not simply answered. Several alternative skin classification models have been proposed to improve the sensitivity and specificity of identifying patients with skin of color (Table). Refining FST classification is one approach. Employing terms such as skin irritation, tenderness, itching, or skin becoming darker from sun exposure rather than painful burn or tanning may result in better identification.^1,4 A study conducted in India modified the FST questionnaire to acknowledge cultural behaviors.¹⁵ Because lighter skin is culturally valued in this population, patient experience with purposeful sun exposure was limited; thus, the questionnaire was modified to remove questions on the use of tanning booths and/or creams as well as sun exposure and instead included more objective questions regarding dark brown eye color, black and dark brown hair color, and dark brown skin color.¹⁵ Other studies have suggested that patient-reported photosensitivity assessed via a questionnaire is a valid measure for assessing FST but is associated with an overestimation of skin color, known as “the dark shift.”²⁰

Conclusion

Other investigators have criticized the various limitations of FST, including physician vs patient assessment, interview vs questionnaire, and phrasing of questions on skin type.²³ Our findings suggest that medical providers should be cognizant of conflating race and ethnicity with FST. Two authors of this report (O.R.W. and J.E.D.) are medical students with skin of color and frequently have observed the addition of FST to the medical records of patients who were not receiving phototherapy as a proxy for race. We believe that more culturally appropriate and clinically relevant methods for describing skin of color need to be developed and, in the interim, the original intent of FST should be emphasized and incorporated in medical school and resident education.

Acknowledgment
The authors thank Adewole Adamson, MD (Austin, Texas), for discussion and feedback.

Fitzpatrick skin type (FST) is the most commonly used classification system in dermatologic practice. It was developed by Thomas B. Fitzpatrick, MD, PhD, in 1975 to assess the propensity of the skin to burn during phototherapy.¹ Fitzpatrick skin type also can be used to assess the clinical benefits and efficacy of cosmetic procedures, including laser hair removal, chemical peel and dermabrasion, tattoo removal, spray tanning, and laser resurfacing for acne scarring.² The original FST classifications included skin types I through IV; skin types V and VI were later added to include individuals of Asian, Indian, and African origin.¹ As a result, FST often is used by providers as a means of describing constitutive skin color and ethnicity.³

How did FST transition from describing the propensity of the skin to burn from UV light exposure to categorizing skin color, thereby becoming a proxy for race? It most likely occurred because there has not been another widely adopted classification system for describing skin color that can be applied to all skin types. Even when the FST classification scale is used as intended, there are inconsistencies with its accuracy; for example, self-reported FSTs have correlated poorly with sunburn risk as well as physician-reported FSTs.^4,5 Although physician-reported FSTs have been demonstrated to correlate with race, race does not consistently correlate with objective measures of pigmentation or self-reported FSTs.⁵ For example, Japanese women often self-identify as FST type II, but Asian skin generally is considered to be nonwhite.¹ Fitzpatrick himself acknowledged that race and ethnicity are cultural and political terms with no scientific basis.⁶ Fitzpatrick skin type also has been demonstrated to correlate poorly with constitutive skin color and minimal erythema dose values.⁷

We conducted an anonymous survey of dermatologists and dermatology trainees to evaluate how providers use FST in their clinical practice as well as how it is used to describe race and ethnicity.

Methods

The survey was distributed electronically to dermatologists and dermatology trainees from March 13 to March 28, 2019, using the Association of Professors of Dermatology listserv, as well as in person at the annual Skin of Color Society meeting in Washington, DC, on February 28, 2019. The 8-item survey included questions about physician demographics (ie, primary practice setting, board certification, and geographic location); whether the respondent identified as an individual with skin of color; and how the respondent utilized FST in clinical notes (ie, describing race/ethnicity, skin cancer risk, and constitutive [baseline] skin color; determining initial phototherapy dosage and suitability for laser treatments, and likelihood of skin burning). A t test was used to determine whether dermatologists who identified as having skin of color utilized FST differently.

Results

A total of 141 surveys were returned, and 140 respondents were included in the final analysis. Given the methods used to distribute the survey, a response rate could not be calculated. The respondents included more board-certified dermatologists (70%) than dermatology trainees (30%). Ninety-three percent of respondents indicated an academic institution as their primary practice location. Notably, 26% of respondents self-identified as having skin of color.

Forty-one percent of all respondents agreed that FST should be included in their clinical documentation. In response to the question “In what scenarios would you refer to FST in a clinical note?” 31% said they used FST to describe patients’ race or ethnicity, 47% used it to describe patients’ constitutive skin color, and 22% utilized it in both scenarios. Respondents who did not identify as having skin of color were more likely to use FST to describe constitutive skin color, though this finding was not statistically significant (P=.063). Anecdotally, providers also included FST in clinical notes on postinflammatory hyperpigmentation, melasma, and treatment with cryotherapy.

Comment

The US Census Bureau has estimated that half of the US population will be of non-European descent by 2050.⁸ As racial and ethnic distinctions continue to be blurred, attempts to include all nonwhite skin types under the umbrella term skin of color becomes increasingly problematic. The true number of skin colors is unknown but likely is infinite, as Brazilian artist Angélica Dass has demonstrated with her photographic project “Humanae” (Figure). Given this shift in demographics and the limitations of the FST, alternative methods of describing skin color must be developed.

The results of our survey suggest that approximately one-third to half of academic dermatologists/dermatology trainees use FST to describe race/ethnicity and/or constitutive skin color. This misuse of FST may occur more frequently among physicians who do not identify as having skin of color. Additionally, misuse of FST in academic settings may be problematic and confusing for medical students who may learn to use this common dermatologic tool outside of its original intent.

We acknowledge that the conundrum of how to classify individuals with nonwhite skin or skin of color is not simply answered. Several alternative skin classification models have been proposed to improve the sensitivity and specificity of identifying patients with skin of color (Table). Refining FST classification is one approach. Employing terms such as skin irritation, tenderness, itching, or skin becoming darker from sun exposure rather than painful burn or tanning may result in better identification.^1,4 A study conducted in India modified the FST questionnaire to acknowledge cultural behaviors.¹⁵ Because lighter skin is culturally valued in this population, patient experience with purposeful sun exposure was limited; thus, the questionnaire was modified to remove questions on the use of tanning booths and/or creams as well as sun exposure and instead included more objective questions regarding dark brown eye color, black and dark brown hair color, and dark brown skin color.¹⁵ Other studies have suggested that patient-reported photosensitivity assessed via a questionnaire is a valid measure for assessing FST but is associated with an overestimation of skin color, known as “the dark shift.”²⁰

Conclusion

Other investigators have criticized the various limitations of FST, including physician vs patient assessment, interview vs questionnaire, and phrasing of questions on skin type.²³ Our findings suggest that medical providers should be cognizant of conflating race and ethnicity with FST. Two authors of this report (O.R.W. and J.E.D.) are medical students with skin of color and frequently have observed the addition of FST to the medical records of patients who were not receiving phototherapy as a proxy for race. We believe that more culturally appropriate and clinically relevant methods for describing skin of color need to be developed and, in the interim, the original intent of FST should be emphasized and incorporated in medical school and resident education.

Acknowledgment
The authors thank Adewole Adamson, MD (Austin, Texas), for discussion and feedback.

Fitzpatrick skin type (FST) is the most commonly used classification system in dermatologic practice. It was developed by Thomas B. Fitzpatrick, MD, PhD, in 1975 to assess the propensity of the skin to burn during phototherapy.¹ Fitzpatrick skin type also can be used to assess the clinical benefits and efficacy of cosmetic procedures, including laser hair removal, chemical peel and dermabrasion, tattoo removal, spray tanning, and laser resurfacing for acne scarring.² The original FST classifications included skin types I through IV; skin types V and VI were later added to include individuals of Asian, Indian, and African origin.¹ As a result, FST often is used by providers as a means of describing constitutive skin color and ethnicity.³

How did FST transition from describing the propensity of the skin to burn from UV light exposure to categorizing skin color, thereby becoming a proxy for race? It most likely occurred because there has not been another widely adopted classification system for describing skin color that can be applied to all skin types. Even when the FST classification scale is used as intended, there are inconsistencies with its accuracy; for example, self-reported FSTs have correlated poorly with sunburn risk as well as physician-reported FSTs.^4,5 Although physician-reported FSTs have been demonstrated to correlate with race, race does not consistently correlate with objective measures of pigmentation or self-reported FSTs.⁵ For example, Japanese women often self-identify as FST type II, but Asian skin generally is considered to be nonwhite.¹ Fitzpatrick himself acknowledged that race and ethnicity are cultural and political terms with no scientific basis.⁶ Fitzpatrick skin type also has been demonstrated to correlate poorly with constitutive skin color and minimal erythema dose values.⁷

We conducted an anonymous survey of dermatologists and dermatology trainees to evaluate how providers use FST in their clinical practice as well as how it is used to describe race and ethnicity.

Methods

The survey was distributed electronically to dermatologists and dermatology trainees from March 13 to March 28, 2019, using the Association of Professors of Dermatology listserv, as well as in person at the annual Skin of Color Society meeting in Washington, DC, on February 28, 2019. The 8-item survey included questions about physician demographics (ie, primary practice setting, board certification, and geographic location); whether the respondent identified as an individual with skin of color; and how the respondent utilized FST in clinical notes (ie, describing race/ethnicity, skin cancer risk, and constitutive [baseline] skin color; determining initial phototherapy dosage and suitability for laser treatments, and likelihood of skin burning). A t test was used to determine whether dermatologists who identified as having skin of color utilized FST differently.

Results

A total of 141 surveys were returned, and 140 respondents were included in the final analysis. Given the methods used to distribute the survey, a response rate could not be calculated. The respondents included more board-certified dermatologists (70%) than dermatology trainees (30%). Ninety-three percent of respondents indicated an academic institution as their primary practice location. Notably, 26% of respondents self-identified as having skin of color.

Forty-one percent of all respondents agreed that FST should be included in their clinical documentation. In response to the question “In what scenarios would you refer to FST in a clinical note?” 31% said they used FST to describe patients’ race or ethnicity, 47% used it to describe patients’ constitutive skin color, and 22% utilized it in both scenarios. Respondents who did not identify as having skin of color were more likely to use FST to describe constitutive skin color, though this finding was not statistically significant (P=.063). Anecdotally, providers also included FST in clinical notes on postinflammatory hyperpigmentation, melasma, and treatment with cryotherapy.

Comment

The US Census Bureau has estimated that half of the US population will be of non-European descent by 2050.⁸ As racial and ethnic distinctions continue to be blurred, attempts to include all nonwhite skin types under the umbrella term skin of color becomes increasingly problematic. The true number of skin colors is unknown but likely is infinite, as Brazilian artist Angélica Dass has demonstrated with her photographic project “Humanae” (Figure). Given this shift in demographics and the limitations of the FST, alternative methods of describing skin color must be developed.

The results of our survey suggest that approximately one-third to half of academic dermatologists/dermatology trainees use FST to describe race/ethnicity and/or constitutive skin color. This misuse of FST may occur more frequently among physicians who do not identify as having skin of color. Additionally, misuse of FST in academic settings may be problematic and confusing for medical students who may learn to use this common dermatologic tool outside of its original intent.

We acknowledge that the conundrum of how to classify individuals with nonwhite skin or skin of color is not simply answered. Several alternative skin classification models have been proposed to improve the sensitivity and specificity of identifying patients with skin of color (Table). Refining FST classification is one approach. Employing terms such as skin irritation, tenderness, itching, or skin becoming darker from sun exposure rather than painful burn or tanning may result in better identification.^1,4 A study conducted in India modified the FST questionnaire to acknowledge cultural behaviors.¹⁵ Because lighter skin is culturally valued in this population, patient experience with purposeful sun exposure was limited; thus, the questionnaire was modified to remove questions on the use of tanning booths and/or creams as well as sun exposure and instead included more objective questions regarding dark brown eye color, black and dark brown hair color, and dark brown skin color.¹⁵ Other studies have suggested that patient-reported photosensitivity assessed via a questionnaire is a valid measure for assessing FST but is associated with an overestimation of skin color, known as “the dark shift.”²⁰

Conclusion

Other investigators have criticized the various limitations of FST, including physician vs patient assessment, interview vs questionnaire, and phrasing of questions on skin type.²³ Our findings suggest that medical providers should be cognizant of conflating race and ethnicity with FST. Two authors of this report (O.R.W. and J.E.D.) are medical students with skin of color and frequently have observed the addition of FST to the medical records of patients who were not receiving phototherapy as a proxy for race. We believe that more culturally appropriate and clinically relevant methods for describing skin of color need to be developed and, in the interim, the original intent of FST should be emphasized and incorporated in medical school and resident education.

Acknowledgment
The authors thank Adewole Adamson, MD (Austin, Texas), for discussion and feedback.

A new line of Barbie dolls unveiled by Mattel earlier this month includes one with vitiligo, much to the delight of clinicians who treat children and adolescents with the condition.

Mattel, Inc.

“When I see young children and adolescents with vitiligo, it is very common for me to feel their emotional suffering from their skin condition,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center in Dallas said in an interview. “Kids can be cruel. Name calling, social ostracizing, [and] effects on self-esteem are all things I have seen amongst my patients and their families in their own struggles with vitiligo.”

According to a brand communications representative from toymaker Mattel, which began manufacturing Barbie dolls in 1959, the company worked with a board-certified dermatologist to include a doll with vitiligo in its 2020 “Fashionistas” line. “As we continue to redefine what it means to be a ‘Barbie’ or look like Barbie, offering a doll with vitiligo in our main doll line allows kids to play out even more stories they see in the world around them,” the representative wrote in an email message. Other dolls debuting as part of the lineup include one with no hair, one with a darker skin tone that uses a gold prosthetic limb, and a Ken doll with long rooted hair (think Jeff Spicoli in “Fast Times at Ridgemont High,” but about six inches longer).

Such efforts to celebrate diversity and inclusiveness go far in helping children and young adults to embrace their skin and their own identities, said Dr. Desai, the immediate past president of the Skin of Color Society and a member of the American Academy of Dermatology board of directors. “One nuance, perhaps even more important, is that the Barbie can help to break down barriers, create awareness, and potentially even reduce bullying, stigma, and lack of knowledge about vitiligo amongst the general public who don’t understand vitiligo,” he said. “I hope the public and social media will embrace this new Barbie. Who knows? Pretty soon, vitiligo may no longer be a ‘thing’ that causes ‘stares’ and ‘glares.’ ”

Referring to the Barbie with no hair in the new line of dolls, the Mattel statement said, “ if a girl is experiencing hair loss for any reason, she can see herself reflected in the line.”

Mattel, Inc.

In 2019, Mattel introduced a lineup of Barbie dolls reflecting permanent disabilities, including one with a prosthetic limb. For that effort, the company collaborated with then-12-year-old Jordan Reeves, the “Born Just Right” coauthor “who is on a mission to build creative solutions that help kids with disabilities, to create a play experience that is as representative as possible,” the Mattel representative wrote.

dbrunk@mdedge.com

A new line of Barbie dolls unveiled by Mattel earlier this month includes one with vitiligo, much to the delight of clinicians who treat children and adolescents with the condition.

Mattel, Inc.

“When I see young children and adolescents with vitiligo, it is very common for me to feel their emotional suffering from their skin condition,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center in Dallas said in an interview. “Kids can be cruel. Name calling, social ostracizing, [and] effects on self-esteem are all things I have seen amongst my patients and their families in their own struggles with vitiligo.”

According to a brand communications representative from toymaker Mattel, which began manufacturing Barbie dolls in 1959, the company worked with a board-certified dermatologist to include a doll with vitiligo in its 2020 “Fashionistas” line. “As we continue to redefine what it means to be a ‘Barbie’ or look like Barbie, offering a doll with vitiligo in our main doll line allows kids to play out even more stories they see in the world around them,” the representative wrote in an email message. Other dolls debuting as part of the lineup include one with no hair, one with a darker skin tone that uses a gold prosthetic limb, and a Ken doll with long rooted hair (think Jeff Spicoli in “Fast Times at Ridgemont High,” but about six inches longer).

Such efforts to celebrate diversity and inclusiveness go far in helping children and young adults to embrace their skin and their own identities, said Dr. Desai, the immediate past president of the Skin of Color Society and a member of the American Academy of Dermatology board of directors. “One nuance, perhaps even more important, is that the Barbie can help to break down barriers, create awareness, and potentially even reduce bullying, stigma, and lack of knowledge about vitiligo amongst the general public who don’t understand vitiligo,” he said. “I hope the public and social media will embrace this new Barbie. Who knows? Pretty soon, vitiligo may no longer be a ‘thing’ that causes ‘stares’ and ‘glares.’ ”

Referring to the Barbie with no hair in the new line of dolls, the Mattel statement said, “ if a girl is experiencing hair loss for any reason, she can see herself reflected in the line.”

Mattel, Inc.

In 2019, Mattel introduced a lineup of Barbie dolls reflecting permanent disabilities, including one with a prosthetic limb. For that effort, the company collaborated with then-12-year-old Jordan Reeves, the “Born Just Right” coauthor “who is on a mission to build creative solutions that help kids with disabilities, to create a play experience that is as representative as possible,” the Mattel representative wrote.

dbrunk@mdedge.com

A new line of Barbie dolls unveiled by Mattel earlier this month includes one with vitiligo, much to the delight of clinicians who treat children and adolescents with the condition.

Mattel, Inc.

“When I see young children and adolescents with vitiligo, it is very common for me to feel their emotional suffering from their skin condition,” Seemal R. Desai, MD, a dermatologist at the University of Texas Southwestern Medical Center in Dallas said in an interview. “Kids can be cruel. Name calling, social ostracizing, [and] effects on self-esteem are all things I have seen amongst my patients and their families in their own struggles with vitiligo.”

According to a brand communications representative from toymaker Mattel, which began manufacturing Barbie dolls in 1959, the company worked with a board-certified dermatologist to include a doll with vitiligo in its 2020 “Fashionistas” line. “As we continue to redefine what it means to be a ‘Barbie’ or look like Barbie, offering a doll with vitiligo in our main doll line allows kids to play out even more stories they see in the world around them,” the representative wrote in an email message. Other dolls debuting as part of the lineup include one with no hair, one with a darker skin tone that uses a gold prosthetic limb, and a Ken doll with long rooted hair (think Jeff Spicoli in “Fast Times at Ridgemont High,” but about six inches longer).

Such efforts to celebrate diversity and inclusiveness go far in helping children and young adults to embrace their skin and their own identities, said Dr. Desai, the immediate past president of the Skin of Color Society and a member of the American Academy of Dermatology board of directors. “One nuance, perhaps even more important, is that the Barbie can help to break down barriers, create awareness, and potentially even reduce bullying, stigma, and lack of knowledge about vitiligo amongst the general public who don’t understand vitiligo,” he said. “I hope the public and social media will embrace this new Barbie. Who knows? Pretty soon, vitiligo may no longer be a ‘thing’ that causes ‘stares’ and ‘glares.’ ”

Referring to the Barbie with no hair in the new line of dolls, the Mattel statement said, “ if a girl is experiencing hair loss for any reason, she can see herself reflected in the line.”

Mattel, Inc.

In 2019, Mattel introduced a lineup of Barbie dolls reflecting permanent disabilities, including one with a prosthetic limb. For that effort, the company collaborated with then-12-year-old Jordan Reeves, the “Born Just Right” coauthor “who is on a mission to build creative solutions that help kids with disabilities, to create a play experience that is as representative as possible,” the Mattel representative wrote.

dbrunk@mdedge.com

A dermatologist-led nonprofit organization has entered into a partnership with the United Nations to achieve global progress towards greater inclusivity for people with albinism.

Courtesy NYDG Foundation

Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.

“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.

Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
 

Striving to do good work

Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.

Stephanie Sinclair, courtesy NYDG Foundation

Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.

“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.

“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.

Courtesy Dr. David Colbert

Philanthropic work in dermatology

Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.

“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.

He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”

Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.

“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”

Dr. Colbert reported that he has no relevant conflicts of interest.
 

Standing Voice also provides resources in East Africa

The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.

Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

koakes@mdedge.com

A dermatologist-led nonprofit organization has entered into a partnership with the United Nations to achieve global progress towards greater inclusivity for people with albinism.

Courtesy NYDG Foundation

Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.

“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.

Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
 

Striving to do good work

Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.

Stephanie Sinclair, courtesy NYDG Foundation

Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.

“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.

“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.

Courtesy Dr. David Colbert

Philanthropic work in dermatology

Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.

“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.

He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”

Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.

“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”

Dr. Colbert reported that he has no relevant conflicts of interest.
 

Standing Voice also provides resources in East Africa

The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.

Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

koakes@mdedge.com

A dermatologist-led nonprofit organization has entered into a partnership with the United Nations to achieve global progress towards greater inclusivity for people with albinism.

Courtesy NYDG Foundation

Representatives from the New York–based NYDG Foundation, including dermatologist David Colbert, MD, recently signed the agreement with the United Nations High Commissioner for Human Rights. At the center of the inclusivity efforts is the foundation’s ColorFull campaign, which aims to shape a collective response to the discrimination and violence that individuals with albinism face around the world.

“We really need to build more inclusive and communal health care systems for all. Partnering with the United Nations will help us to reach our goals and build stronger bonds with those health care providers working with one of the most marginalized and vulnerable groups in Africa,” Dr. Colbert said in an interview.

Stylish images of individuals with albinism, including prominent model Diandra Forrest, anchor the ColorFull campaign’s messaging; Ms. Forrest is featured in a video posted by the United Nations in November announcing the joint human rights campaign. Because the consequences of albinism can be deadly serious for affected individuals in many parts of the world, awareness is desperately needed, participants in NYDG’s work and in Standing Voice, another nonprofit that provides resources for people with albinism in East Africa, emphasized in interviews.
 

Striving to do good work

Stephan Bognar, a seasoned leader of international nonprofits, has teamed up with Dr. Colbert, NYDG Foundation’s founding physician, to craft the international campaign to raise awareness of albinism and increase acceptance of those with the condition. “You don’t always have to stand alone to break down the walls of exclusion. The fight for social justice and human rights for persons with albinism requires a collective responsibility,” Mr. Bognar said in an interview.

Stephanie Sinclair, courtesy NYDG Foundation

Dr. Colbert, senior partner of the New York Dermatology Group, a large Manhattan-based practice, founded the nonprofit when he became involved in wound-care efforts in Haiti following the 2010 earthquake. The foundation has since supported such philanthropic efforts as helping people with albinism, offering scholarships, and raising awareness of the importance of sun protection among youth athletes.

“One day, 3 years ago or so, I was reading the New York Times and I came across this article – it was called ‘The Hunted,’ ” Dr. Colbert recalled. “It was something I knew nothing about. In Eastern Africa, people with albinism are often hunted down for body parts and their lives are at risk” from being hunted and murdered – but also because their body parts are used for witchcraft and magic, he noted.

“I was captivated by that, and I remember I called Stephan, and I said, ‘I have a project for you.’ ” Because of extensive previous work with international nongovernmental organizations and the United Nations, Mr. Bognar, who is now the executive director of the NYDG Foundation, “had the pedigree to make things happen instead of spinning our wheels,” Dr. Colbert said.

Courtesy Dr. David Colbert

Philanthropic work in dermatology

Despite his busy practice, Dr. Colbert said he has found great satisfaction in pursuing philanthropic work. For physicians considering similar efforts, he said that genuine engagement with the issue is critical and global travel isn’t necessary to make a real difference.

“I think that, first, this should be something that you’re interested in and that you have the means to make some impact,” Dr. Colbert said. “Doing something doesn’t need to be a global campaign. You don’t need to have a home run – every little thing counts. Catching one squamous cell cancer on one patient with albinism makes a difference. But if you want to go bigger, you have to look at your community and see who has the resources and who might also be interested” in a cause you’re passionate about.

He added that a busy physician shouldn’t expect to do it all. “You have to find the right partner because we as physicians are taking care of our patients and paying the rent, so taking on a partner who is trained to do that can ... help you achieve what you envision.”

Though the NYDG Foundation has funded trips to Africa and participates in teledermatology there, Dr. Colbert said that the awareness campaign the NYDG is cosponsoring with the United Nations is of fundamental importance as well. “This is a really great example of the positive impact that social media can have on our society – in a good way, instead of a negative or self-serving way,” he said.

“I think that the ColorFull campaign will normalize the idea of people who are living without melanin in their skin. It keeps it out of the realm of ‘Don’t say anything.’ People don’t know what it means, so if we bring out the science, and show successful people who have normal lives, who have children, and we explain what it is, it demystifies it – and everybody wins. ... We’re all just people, no matter how many melanin granules we have.”

Dr. Colbert reported that he has no relevant conflicts of interest.
 

Standing Voice also provides resources in East Africa

The work of other nongovernmental organizations is also making a difference for people in East Africa with albinism.

Standing Voice is a United Kingdom–based nonprofit that provides education and resources that include sunscreen, as well as assessment and treatment of skin conditions for people with albinism in Tanzania and Malawi.

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

Courtesy Standing Voice

koakes@mdedge.com

A low-density nonablative laser successfully treated postinflammatory hyperpigmentation (PIH) in a group of patients with darker skin types, Yoon‐Soo Cindy Bae, MD, and colleagues reported.

Among patients treated with the nonablative fractional 1,927 nm laser, there was a mean improvement of about 43% in hyperpigmented areas, and no side effects were reported, wrote Dr. Bae, of the department of dermatology at New York University and the Laser & Skin Surgery Center of New York, and coauthors in Lasers in Surgery and Medicine.

Lasers have not been the first choice for hyperpigmentation in Fitzpatrick skin types IV, V, and VI, they pointed out. More commonly used treatments are hydroquinone and chemical peels that use glycolic acid or salicylic acid. But these are not always ideal options, Dr. Bae said in an interview.

“There are side effects to medical therapy. The drawbacks of medical therapy include compliance issues, risk of skin irritation from the product ... and a risk of hyperpigmentation specifically for hydroquinone. There are also risks to laser therapy, including dyspigmentation and scarring,” she added. “However, the laser we used is a low energy, nonablative type of laser, so the risk of scarring is extremely rare and the dyspigmentation is actually what we are aiming to treat.”

The retrospective study comprised 61 patients with PIH who had received more than one treatment with the low energy fractionated 1,927 nm diode laser between 2013 and 2016. Most were Fitzpatrick type IV (73.8%). The remainder were Type V (16.4%) and Type VI (9.8%). The most common treatment site was the face or cheeks (68.9%), followed by legs (13%), the rest of the cases were unspecified.

Patients had received treatment with the laser with fixed fluence at 5 mJ, fixed spot size of 140 micrometers, depth of 170 micrometers, and 5% coverage. They required several treatments: 15 had two, 14 had three, 16 had four, and the remainder had five or more. Topical treatment data were not collected. Photographs taken before treatment and before the last treatment were evaluated by dermatologists who had not treated the patients. Based on those evaluations, the mean improvement was a statistically significant 43.2%.

There did not, however, appear to be much difference between the treatment groups. The mean improvement among patients with two treatments was 44.5%; three treatments, 44.29%; four treatments, 40.63%; five or more treatments, 43.75%.

Although those with darker skin types tended to have better results, there were no statistically significant differences between the skin-type groups. Among those with Fitzpatrick skin type IV, the mean improvement was 40.39%; skin type V, 47.25%; and skin type VI, 57.92%.

“The fact that there was no correlation between Fitzpatrick skin type … and average percent improvement demonstrates that this laser is a viable treatment option for patients with very dark skin,” the authors wrote. “There were also no significant differences between the average percent improvements for people receiving different numbers of treatments. A trend was observed that favored treating patients with darker skin type; however, this lacked statistical significance. This may have been due to an underpowered study.”

Limitations of the study included the retrospective design and nonstandardization of photographs; “further studies with prospective controlled designs are needed to confirm our findings,” they added.

No funding or disclosure information was provided.

msullivan@mdedge.com

SOURCE: Bae YS et al. Lasers Surg Med. 2019 Oct 29. doi: 10.1002/lsm.23173.

A low-density nonablative laser successfully treated postinflammatory hyperpigmentation (PIH) in a group of patients with darker skin types, Yoon‐Soo Cindy Bae, MD, and colleagues reported.

Among patients treated with the nonablative fractional 1,927 nm laser, there was a mean improvement of about 43% in hyperpigmented areas, and no side effects were reported, wrote Dr. Bae, of the department of dermatology at New York University and the Laser & Skin Surgery Center of New York, and coauthors in Lasers in Surgery and Medicine.

Lasers have not been the first choice for hyperpigmentation in Fitzpatrick skin types IV, V, and VI, they pointed out. More commonly used treatments are hydroquinone and chemical peels that use glycolic acid or salicylic acid. But these are not always ideal options, Dr. Bae said in an interview.

“There are side effects to medical therapy. The drawbacks of medical therapy include compliance issues, risk of skin irritation from the product ... and a risk of hyperpigmentation specifically for hydroquinone. There are also risks to laser therapy, including dyspigmentation and scarring,” she added. “However, the laser we used is a low energy, nonablative type of laser, so the risk of scarring is extremely rare and the dyspigmentation is actually what we are aiming to treat.”

The retrospective study comprised 61 patients with PIH who had received more than one treatment with the low energy fractionated 1,927 nm diode laser between 2013 and 2016. Most were Fitzpatrick type IV (73.8%). The remainder were Type V (16.4%) and Type VI (9.8%). The most common treatment site was the face or cheeks (68.9%), followed by legs (13%), the rest of the cases were unspecified.

Patients had received treatment with the laser with fixed fluence at 5 mJ, fixed spot size of 140 micrometers, depth of 170 micrometers, and 5% coverage. They required several treatments: 15 had two, 14 had three, 16 had four, and the remainder had five or more. Topical treatment data were not collected. Photographs taken before treatment and before the last treatment were evaluated by dermatologists who had not treated the patients. Based on those evaluations, the mean improvement was a statistically significant 43.2%.

There did not, however, appear to be much difference between the treatment groups. The mean improvement among patients with two treatments was 44.5%; three treatments, 44.29%; four treatments, 40.63%; five or more treatments, 43.75%.

Although those with darker skin types tended to have better results, there were no statistically significant differences between the skin-type groups. Among those with Fitzpatrick skin type IV, the mean improvement was 40.39%; skin type V, 47.25%; and skin type VI, 57.92%.

“The fact that there was no correlation between Fitzpatrick skin type … and average percent improvement demonstrates that this laser is a viable treatment option for patients with very dark skin,” the authors wrote. “There were also no significant differences between the average percent improvements for people receiving different numbers of treatments. A trend was observed that favored treating patients with darker skin type; however, this lacked statistical significance. This may have been due to an underpowered study.”

Limitations of the study included the retrospective design and nonstandardization of photographs; “further studies with prospective controlled designs are needed to confirm our findings,” they added.

No funding or disclosure information was provided.

msullivan@mdedge.com

SOURCE: Bae YS et al. Lasers Surg Med. 2019 Oct 29. doi: 10.1002/lsm.23173.

A low-density nonablative laser successfully treated postinflammatory hyperpigmentation (PIH) in a group of patients with darker skin types, Yoon‐Soo Cindy Bae, MD, and colleagues reported.

Among patients treated with the nonablative fractional 1,927 nm laser, there was a mean improvement of about 43% in hyperpigmented areas, and no side effects were reported, wrote Dr. Bae, of the department of dermatology at New York University and the Laser & Skin Surgery Center of New York, and coauthors in Lasers in Surgery and Medicine.

Lasers have not been the first choice for hyperpigmentation in Fitzpatrick skin types IV, V, and VI, they pointed out. More commonly used treatments are hydroquinone and chemical peels that use glycolic acid or salicylic acid. But these are not always ideal options, Dr. Bae said in an interview.

“There are side effects to medical therapy. The drawbacks of medical therapy include compliance issues, risk of skin irritation from the product ... and a risk of hyperpigmentation specifically for hydroquinone. There are also risks to laser therapy, including dyspigmentation and scarring,” she added. “However, the laser we used is a low energy, nonablative type of laser, so the risk of scarring is extremely rare and the dyspigmentation is actually what we are aiming to treat.”

The retrospective study comprised 61 patients with PIH who had received more than one treatment with the low energy fractionated 1,927 nm diode laser between 2013 and 2016. Most were Fitzpatrick type IV (73.8%). The remainder were Type V (16.4%) and Type VI (9.8%). The most common treatment site was the face or cheeks (68.9%), followed by legs (13%), the rest of the cases were unspecified.

Patients had received treatment with the laser with fixed fluence at 5 mJ, fixed spot size of 140 micrometers, depth of 170 micrometers, and 5% coverage. They required several treatments: 15 had two, 14 had three, 16 had four, and the remainder had five or more. Topical treatment data were not collected. Photographs taken before treatment and before the last treatment were evaluated by dermatologists who had not treated the patients. Based on those evaluations, the mean improvement was a statistically significant 43.2%.

There did not, however, appear to be much difference between the treatment groups. The mean improvement among patients with two treatments was 44.5%; three treatments, 44.29%; four treatments, 40.63%; five or more treatments, 43.75%.

Although those with darker skin types tended to have better results, there were no statistically significant differences between the skin-type groups. Among those with Fitzpatrick skin type IV, the mean improvement was 40.39%; skin type V, 47.25%; and skin type VI, 57.92%.

“The fact that there was no correlation between Fitzpatrick skin type … and average percent improvement demonstrates that this laser is a viable treatment option for patients with very dark skin,” the authors wrote. “There were also no significant differences between the average percent improvements for people receiving different numbers of treatments. A trend was observed that favored treating patients with darker skin type; however, this lacked statistical significance. This may have been due to an underpowered study.”

Limitations of the study included the retrospective design and nonstandardization of photographs; “further studies with prospective controlled designs are needed to confirm our findings,” they added.

No funding or disclosure information was provided.

msullivan@mdedge.com

SOURCE: Bae YS et al. Lasers Surg Med. 2019 Oct 29. doi: 10.1002/lsm.23173.

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

bjancin@mdedge.com

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

bjancin@mdedge.com

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

bjancin@mdedge.com

The Diagnosis: Bleomycin-Induced Flagellate Hyperpigmentation 

Histopathology of the affected skin demonstrated a slight increase in collagen bundle thickness, a chronic dermal perivascular inflammation, and associated pigment incontinence with dermal melanophages compared to unaffected skin (Figure). CD34 was faintly decreased, and dermal mucin increased in affected skin. This postinflammatory pigmentary alteration with subtle dermal sclerosis had persisted unchanged for more than 5 years after cessation of bleomycin therapy. Topical hydroquinone, physical blocker photoprotection, and laser modalities such as the Q-switched alexandrite (755-nm)/Nd:YAG (1064-nm) and ablative CO₂ resurfacing lasers were attempted with minimal overall impact on cosmesis. 

Bleomycin is a chemotherapeutic antibiotic that has been commonly used to treat Hodgkin lymphoma, germ cell tumors, and recurrent malignant pleural effusions.¹ The drug is inactivated in most tissues by the enzyme bleomycin hydrolase. This enzyme is not present in skin and lung tissue; as a result, these organs are the most common sites of bleomycin toxicity.¹ There are a variety of cutaneous effects associated with bleomycin including alopecia, hyperpigmentation, acral erythema, Raynaud phenomenon, and nail dystrophy.² Flagellate hyperpigmentation is a less common cutaneous toxicity. It is an unusual eruption that appears as whiplike linear streaks on the upper chest and back, limbs, and flanks.³ This cutaneous manifestation was once thought to be specific to bleomycin use; however, it also has been described in dermatomyositis, adult-onset Still disease, and after the ingestion of uncooked or undercooked shiitake mushrooms.⁴ Flagellate hyperpigmentation also was once thought to be dose dependent; however, it has been described in even very small doses.⁵ The eruption has been described as independent of the route of drug administration, appearing with intravenous, subcutaneous, and intramuscular bleomycin.² The association of bleomycin and flagellate hyperpigmentation has been reported since 1970; however, it is less commonly seen in clinical practice with the declining use of bleomycin.¹  

The exact mechanism for the hyperpigmentation is unknown. It has been proposed that the linear lesions are related to areas of pruritus and subsequent excoriations.¹ Dermatographism may be present to a limited extent, but it is unlikely to be a chief cause of flagellate hyperpigmentation, as linear streaks have been reported in the absence of trauma. It also has been proposed that bleomycin has a direct toxic effect on the melanocytes, which stimulates increased melanin secretion.² The hyperpigmentation also may be due to pigmentary incontinence secondary to inflammation.⁵ Histopathologic findings usually are varied and nonspecific.² There may be a deep perivascular lymphocytic infiltrate, which is nonspecific but can be associated with drug-induced pathology.⁴ Bleomycin also is used to induce localized scleroderma in mouse-model research⁶ and has been reported to cause localized scleroderma at an infusion site or after an intralesional injection,^7,8 which is not typically reported in flagellate erythema, but bleomycin's sclerosing effects may have played a role in the visible and sclerosing atrophy noted in our patient. Yamamoto et al⁹ reported a similar case of dermal sclerosis induced by bleomycin.  

Flagellate hyperpigmentation typically lasts for up to 6 months.³ Patients with cutaneous manifestations from bleomycin therapy usually respond to steroid therapy and discontinuation of the drug. Bleomycin re-exposure should be avoided, as it may cause extension or widespread recurrence of flagellate hyperpigmentation.³ Postinflammatory pigment alteration may persist in patients with darker skin types and in patients with dramatic inciting inflammation.  

Atrophoderma of Pasini and Pierini is a form of dermal atrophy that presents with 1 or more sharply demarcated depressed patches. There is some debate whether it is a distinct entity or a primary atrophic morphea.¹⁰ Linear atrophoderma of Moulin has a similar morphology with hyperpigmented depressions and "cliff-drop" borders, but these lesions follow the lines of Blaschko.¹¹ Linear morphea initially can present as a linear erythematous streak but more commonly appears as a plaque-type morphea lesion that forms a scarlike band.¹² Erythema dyschromicum perstans is an ashy dermatosis characterized by gray or blue-brown macules seen in Fitzpatrick skin types III through V and typically is chronic and progressive.¹³  

The Diagnosis: Bleomycin-Induced Flagellate Hyperpigmentation 

Histopathology of the affected skin demonstrated a slight increase in collagen bundle thickness, a chronic dermal perivascular inflammation, and associated pigment incontinence with dermal melanophages compared to unaffected skin (Figure). CD34 was faintly decreased, and dermal mucin increased in affected skin. This postinflammatory pigmentary alteration with subtle dermal sclerosis had persisted unchanged for more than 5 years after cessation of bleomycin therapy. Topical hydroquinone, physical blocker photoprotection, and laser modalities such as the Q-switched alexandrite (755-nm)/Nd:YAG (1064-nm) and ablative CO₂ resurfacing lasers were attempted with minimal overall impact on cosmesis. 

Bleomycin is a chemotherapeutic antibiotic that has been commonly used to treat Hodgkin lymphoma, germ cell tumors, and recurrent malignant pleural effusions.¹ The drug is inactivated in most tissues by the enzyme bleomycin hydrolase. This enzyme is not present in skin and lung tissue; as a result, these organs are the most common sites of bleomycin toxicity.¹ There are a variety of cutaneous effects associated with bleomycin including alopecia, hyperpigmentation, acral erythema, Raynaud phenomenon, and nail dystrophy.² Flagellate hyperpigmentation is a less common cutaneous toxicity. It is an unusual eruption that appears as whiplike linear streaks on the upper chest and back, limbs, and flanks.³ This cutaneous manifestation was once thought to be specific to bleomycin use; however, it also has been described in dermatomyositis, adult-onset Still disease, and after the ingestion of uncooked or undercooked shiitake mushrooms.⁴ Flagellate hyperpigmentation also was once thought to be dose dependent; however, it has been described in even very small doses.⁵ The eruption has been described as independent of the route of drug administration, appearing with intravenous, subcutaneous, and intramuscular bleomycin.² The association of bleomycin and flagellate hyperpigmentation has been reported since 1970; however, it is less commonly seen in clinical practice with the declining use of bleomycin.¹  

The exact mechanism for the hyperpigmentation is unknown. It has been proposed that the linear lesions are related to areas of pruritus and subsequent excoriations.¹ Dermatographism may be present to a limited extent, but it is unlikely to be a chief cause of flagellate hyperpigmentation, as linear streaks have been reported in the absence of trauma. It also has been proposed that bleomycin has a direct toxic effect on the melanocytes, which stimulates increased melanin secretion.² The hyperpigmentation also may be due to pigmentary incontinence secondary to inflammation.⁵ Histopathologic findings usually are varied and nonspecific.² There may be a deep perivascular lymphocytic infiltrate, which is nonspecific but can be associated with drug-induced pathology.⁴ Bleomycin also is used to induce localized scleroderma in mouse-model research⁶ and has been reported to cause localized scleroderma at an infusion site or after an intralesional injection,^7,8 which is not typically reported in flagellate erythema, but bleomycin's sclerosing effects may have played a role in the visible and sclerosing atrophy noted in our patient. Yamamoto et al⁹ reported a similar case of dermal sclerosis induced by bleomycin.  

Flagellate hyperpigmentation typically lasts for up to 6 months.³ Patients with cutaneous manifestations from bleomycin therapy usually respond to steroid therapy and discontinuation of the drug. Bleomycin re-exposure should be avoided, as it may cause extension or widespread recurrence of flagellate hyperpigmentation.³ Postinflammatory pigment alteration may persist in patients with darker skin types and in patients with dramatic inciting inflammation.  

Atrophoderma of Pasini and Pierini is a form of dermal atrophy that presents with 1 or more sharply demarcated depressed patches. There is some debate whether it is a distinct entity or a primary atrophic morphea.¹⁰ Linear atrophoderma of Moulin has a similar morphology with hyperpigmented depressions and "cliff-drop" borders, but these lesions follow the lines of Blaschko.¹¹ Linear morphea initially can present as a linear erythematous streak but more commonly appears as a plaque-type morphea lesion that forms a scarlike band.¹² Erythema dyschromicum perstans is an ashy dermatosis characterized by gray or blue-brown macules seen in Fitzpatrick skin types III through V and typically is chronic and progressive.¹³  

The Diagnosis: Bleomycin-Induced Flagellate Hyperpigmentation 

Histopathology of the affected skin demonstrated a slight increase in collagen bundle thickness, a chronic dermal perivascular inflammation, and associated pigment incontinence with dermal melanophages compared to unaffected skin (Figure). CD34 was faintly decreased, and dermal mucin increased in affected skin. This postinflammatory pigmentary alteration with subtle dermal sclerosis had persisted unchanged for more than 5 years after cessation of bleomycin therapy. Topical hydroquinone, physical blocker photoprotection, and laser modalities such as the Q-switched alexandrite (755-nm)/Nd:YAG (1064-nm) and ablative CO₂ resurfacing lasers were attempted with minimal overall impact on cosmesis. 

Bleomycin is a chemotherapeutic antibiotic that has been commonly used to treat Hodgkin lymphoma, germ cell tumors, and recurrent malignant pleural effusions.¹ The drug is inactivated in most tissues by the enzyme bleomycin hydrolase. This enzyme is not present in skin and lung tissue; as a result, these organs are the most common sites of bleomycin toxicity.¹ There are a variety of cutaneous effects associated with bleomycin including alopecia, hyperpigmentation, acral erythema, Raynaud phenomenon, and nail dystrophy.² Flagellate hyperpigmentation is a less common cutaneous toxicity. It is an unusual eruption that appears as whiplike linear streaks on the upper chest and back, limbs, and flanks.³ This cutaneous manifestation was once thought to be specific to bleomycin use; however, it also has been described in dermatomyositis, adult-onset Still disease, and after the ingestion of uncooked or undercooked shiitake mushrooms.⁴ Flagellate hyperpigmentation also was once thought to be dose dependent; however, it has been described in even very small doses.⁵ The eruption has been described as independent of the route of drug administration, appearing with intravenous, subcutaneous, and intramuscular bleomycin.² The association of bleomycin and flagellate hyperpigmentation has been reported since 1970; however, it is less commonly seen in clinical practice with the declining use of bleomycin.¹  

The exact mechanism for the hyperpigmentation is unknown. It has been proposed that the linear lesions are related to areas of pruritus and subsequent excoriations.¹ Dermatographism may be present to a limited extent, but it is unlikely to be a chief cause of flagellate hyperpigmentation, as linear streaks have been reported in the absence of trauma. It also has been proposed that bleomycin has a direct toxic effect on the melanocytes, which stimulates increased melanin secretion.² The hyperpigmentation also may be due to pigmentary incontinence secondary to inflammation.⁵ Histopathologic findings usually are varied and nonspecific.² There may be a deep perivascular lymphocytic infiltrate, which is nonspecific but can be associated with drug-induced pathology.⁴ Bleomycin also is used to induce localized scleroderma in mouse-model research⁶ and has been reported to cause localized scleroderma at an infusion site or after an intralesional injection,^7,8 which is not typically reported in flagellate erythema, but bleomycin's sclerosing effects may have played a role in the visible and sclerosing atrophy noted in our patient. Yamamoto et al⁹ reported a similar case of dermal sclerosis induced by bleomycin.  

Flagellate hyperpigmentation typically lasts for up to 6 months.³ Patients with cutaneous manifestations from bleomycin therapy usually respond to steroid therapy and discontinuation of the drug. Bleomycin re-exposure should be avoided, as it may cause extension or widespread recurrence of flagellate hyperpigmentation.³ Postinflammatory pigment alteration may persist in patients with darker skin types and in patients with dramatic inciting inflammation.  

Atrophoderma of Pasini and Pierini is a form of dermal atrophy that presents with 1 or more sharply demarcated depressed patches. There is some debate whether it is a distinct entity or a primary atrophic morphea.¹⁰ Linear atrophoderma of Moulin has a similar morphology with hyperpigmented depressions and "cliff-drop" borders, but these lesions follow the lines of Blaschko.¹¹ Linear morphea initially can present as a linear erythematous streak but more commonly appears as a plaque-type morphea lesion that forms a scarlike band.¹² Erythema dyschromicum perstans is an ashy dermatosis characterized by gray or blue-brown macules seen in Fitzpatrick skin types III through V and typically is chronic and progressive.¹³  

To the Editor:

Hyperkeratosis lenticularis perstans (HLP), or Flegel disease, is a rare keratinization disorder characterized by asymptomatic, red-brown, 1- to 5-mm papules with irregular horny scales commonly seen on the dorsal feet and lower legs.¹ Hyperkeratosis lenticularis perstans is notorious for being difficult to treat. Various treatment options, including 5-fluorouracil, topical and oral retinoids, vitamin D₃ derivatives, psoralen plus UVA therapy, and dermabrasion, have been explored but none have proven to be consistently effective.

A woman in her 50s presented with an asymptomatic eruption on the legs and thighs that had been present for the last 20 years. She had been misdiagnosed by multiple outside providers with atopic dermatitis and was treated with topical steroids without considerable improvement. Upon initial presentation to our clinic , physical examination revealed a woman with Fitzpatrick skin type II with multiple hyperpigmented, red-brown, 2- to 6-mm papules on the extensor surfaces of the lower legs and upper thighs (Figure, A). A 3-mm punch biopsy of a lesion on the right upper thigh revealed hyperkeratosis and parakeratosis with basal layer degeneration and a perivascular lymphocytic infiltrate. The clinical and histopathologic findings were consistent with HLP.

The patient was started on treatment with 5-fluorouracil cream on the right leg and tazarotene cream 0.1% on the left leg to determine which agent would work best. After 9 weeks of treatment, slight improvement was observed on both legs, but the lesions were still erythematous (Figure, B). Treatment was continued, and after 14 weeks complete resolution of the lesions was noted on both legs; however, postinflammatory hyperpigmentation (PIH) was observed on the left leg, which had been treated with tazarotene (Figure, C). The patient was lost to follow-up prior to treatment of the PIH.

In PIH, there is either abnormal production or distribution of melanin pigment in the epidermis and/or dermis. Several mechanisms for PIH have been suggested. One potential mechanism is disruption of the basal cell layer due to dermal lymphocytic inflammation, causing melanin to be released and trapped by macrophages present in the dermal papillae. Another possible mechanism is epidermal hypermelanosis, in which the release and oxidation of arachidonic acid to prostaglandins and leukotrienes alters immune cells and melanocytes, causing an increase in melanin and increased transfer of melanin to keratinocytes in the surrounding epidermis.⁴

Treatment of PIH can be a difficult and prolonged process, especially when a dermal rather than epidermal melanosis is observed. Topical retinoids, topical hydroquinone, azelaic acid, corticosteroids, tretinoin cream, glycolic acid, and trichloroacetic acid have been shown to be effective in treating epidermal PIH. Tazarotene is a synthetic retinoid that has been proven to be an effective treatment of PIH³; however, in our patient the PIH progressed with treatment. One plausible explanation is that irritation caused by the medication led to further PIH.^2,5

It is uncommon for tazarotene to cause PIH. Hyperpigmentation is listed as an adverse effect observed during the postmarketing experience according to one manufacturer⁶ and the US Food and Drug Administration; however, details about prior incidents of hyperpigmentation have not been reported in the literature. Our case is unique because both treatments showed considerable improvement in HLP, but more PIH was observed on the tazarotene-treated leg.

To the Editor:

Hyperkeratosis lenticularis perstans (HLP), or Flegel disease, is a rare keratinization disorder characterized by asymptomatic, red-brown, 1- to 5-mm papules with irregular horny scales commonly seen on the dorsal feet and lower legs.¹ Hyperkeratosis lenticularis perstans is notorious for being difficult to treat. Various treatment options, including 5-fluorouracil, topical and oral retinoids, vitamin D₃ derivatives, psoralen plus UVA therapy, and dermabrasion, have been explored but none have proven to be consistently effective.

A woman in her 50s presented with an asymptomatic eruption on the legs and thighs that had been present for the last 20 years. She had been misdiagnosed by multiple outside providers with atopic dermatitis and was treated with topical steroids without considerable improvement. Upon initial presentation to our clinic , physical examination revealed a woman with Fitzpatrick skin type II with multiple hyperpigmented, red-brown, 2- to 6-mm papules on the extensor surfaces of the lower legs and upper thighs (Figure, A). A 3-mm punch biopsy of a lesion on the right upper thigh revealed hyperkeratosis and parakeratosis with basal layer degeneration and a perivascular lymphocytic infiltrate. The clinical and histopathologic findings were consistent with HLP.

The patient was started on treatment with 5-fluorouracil cream on the right leg and tazarotene cream 0.1% on the left leg to determine which agent would work best. After 9 weeks of treatment, slight improvement was observed on both legs, but the lesions were still erythematous (Figure, B). Treatment was continued, and after 14 weeks complete resolution of the lesions was noted on both legs; however, postinflammatory hyperpigmentation (PIH) was observed on the left leg, which had been treated with tazarotene (Figure, C). The patient was lost to follow-up prior to treatment of the PIH.

In PIH, there is either abnormal production or distribution of melanin pigment in the epidermis and/or dermis. Several mechanisms for PIH have been suggested. One potential mechanism is disruption of the basal cell layer due to dermal lymphocytic inflammation, causing melanin to be released and trapped by macrophages present in the dermal papillae. Another possible mechanism is epidermal hypermelanosis, in which the release and oxidation of arachidonic acid to prostaglandins and leukotrienes alters immune cells and melanocytes, causing an increase in melanin and increased transfer of melanin to keratinocytes in the surrounding epidermis.⁴

Treatment of PIH can be a difficult and prolonged process, especially when a dermal rather than epidermal melanosis is observed. Topical retinoids, topical hydroquinone, azelaic acid, corticosteroids, tretinoin cream, glycolic acid, and trichloroacetic acid have been shown to be effective in treating epidermal PIH. Tazarotene is a synthetic retinoid that has been proven to be an effective treatment of PIH³; however, in our patient the PIH progressed with treatment. One plausible explanation is that irritation caused by the medication led to further PIH.^2,5

It is uncommon for tazarotene to cause PIH. Hyperpigmentation is listed as an adverse effect observed during the postmarketing experience according to one manufacturer⁶ and the US Food and Drug Administration; however, details about prior incidents of hyperpigmentation have not been reported in the literature. Our case is unique because both treatments showed considerable improvement in HLP, but more PIH was observed on the tazarotene-treated leg.

To the Editor:

Hyperkeratosis lenticularis perstans (HLP), or Flegel disease, is a rare keratinization disorder characterized by asymptomatic, red-brown, 1- to 5-mm papules with irregular horny scales commonly seen on the dorsal feet and lower legs.¹ Hyperkeratosis lenticularis perstans is notorious for being difficult to treat. Various treatment options, including 5-fluorouracil, topical and oral retinoids, vitamin D₃ derivatives, psoralen plus UVA therapy, and dermabrasion, have been explored but none have proven to be consistently effective.

A woman in her 50s presented with an asymptomatic eruption on the legs and thighs that had been present for the last 20 years. She had been misdiagnosed by multiple outside providers with atopic dermatitis and was treated with topical steroids without considerable improvement. Upon initial presentation to our clinic , physical examination revealed a woman with Fitzpatrick skin type II with multiple hyperpigmented, red-brown, 2- to 6-mm papules on the extensor surfaces of the lower legs and upper thighs (Figure, A). A 3-mm punch biopsy of a lesion on the right upper thigh revealed hyperkeratosis and parakeratosis with basal layer degeneration and a perivascular lymphocytic infiltrate. The clinical and histopathologic findings were consistent with HLP.

The patient was started on treatment with 5-fluorouracil cream on the right leg and tazarotene cream 0.1% on the left leg to determine which agent would work best. After 9 weeks of treatment, slight improvement was observed on both legs, but the lesions were still erythematous (Figure, B). Treatment was continued, and after 14 weeks complete resolution of the lesions was noted on both legs; however, postinflammatory hyperpigmentation (PIH) was observed on the left leg, which had been treated with tazarotene (Figure, C). The patient was lost to follow-up prior to treatment of the PIH.

In PIH, there is either abnormal production or distribution of melanin pigment in the epidermis and/or dermis. Several mechanisms for PIH have been suggested. One potential mechanism is disruption of the basal cell layer due to dermal lymphocytic inflammation, causing melanin to be released and trapped by macrophages present in the dermal papillae. Another possible mechanism is epidermal hypermelanosis, in which the release and oxidation of arachidonic acid to prostaglandins and leukotrienes alters immune cells and melanocytes, causing an increase in melanin and increased transfer of melanin to keratinocytes in the surrounding epidermis.⁴

Treatment of PIH can be a difficult and prolonged process, especially when a dermal rather than epidermal melanosis is observed. Topical retinoids, topical hydroquinone, azelaic acid, corticosteroids, tretinoin cream, glycolic acid, and trichloroacetic acid have been shown to be effective in treating epidermal PIH. Tazarotene is a synthetic retinoid that has been proven to be an effective treatment of PIH³; however, in our patient the PIH progressed with treatment. One plausible explanation is that irritation caused by the medication led to further PIH.^2,5

It is uncommon for tazarotene to cause PIH. Hyperpigmentation is listed as an adverse effect observed during the postmarketing experience according to one manufacturer⁶ and the US Food and Drug Administration; however, details about prior incidents of hyperpigmentation have not been reported in the literature. Our case is unique because both treatments showed considerable improvement in HLP, but more PIH was observed on the tazarotene-treated leg.