MDedge Dermatology

An ancient tree of the Ginkgoaceae family, Ginkgo biloba is known as a living fossil because its genome has been identified in fossils older than 200 million years.¹ An individual tree can live longer than 1000 years. Originating in China, G biloba (here, “ginkgo”) is cultivated worldwide for its attractive foliage (Figure 1). Ginkgo extract has long been used in traditional Chinese medicine; however, contact with the plant proper can provoke allergic contact dermatitis.

Dermatitis-Inducing Components

The allergenic component of the ginkgo tree is ginkgolic acid, which is structurally similar to urushiol and anacardic acid.^2,3 This compound can cause a cross-reaction in a person previously sensitized by contact with other plants. Urushiol is found in poison ivy(Toxicodendron radicans); anacardic acid is found in the cashew tree (Anacardium occidentale). Both plants belong to the family Anacardiaceae, commonly known as the cashew family.

Members of Anacardiaceae are the most common causes of plant-induced allergic contact dermatitis and include the cashew tree, mango tree, poison ivy, poison oak, and poison sumac. These plants can cross-react to cause contact dermatitis (Table).³ Patch tests have revealed that some individuals who are sensitive to components of the ginkgo tree also demonstrate sensitivity to poison ivy and poison sumac^4,5; countering this finding, Lepoittevin and colleagues⁶ demonstrated in animal studies that there was no cross-reactivity between ginkgo and urushiol, suggesting that patients with a reported cross-reaction might truly have been previously sensitized to both plants. In general, patients who have a history of a reaction to any Anacardiaceae plant should take precautions when handling them.

Therapeutic Benefit of Ginkgo

Ginkgo extract is sold as the herbal supplement EGB761, which acts as an antioxidant.⁷ In France, Germany, and China, it is a commonly prescribed herbal medicine.⁸ It is purported to support memory and attention; studies have shown improvement in cognition and in involvement with activities of daily living for patients with dementia.^9,10 Ginkgo extract might lessen peripheral vascular disease and cerebral circulatory disease, having been shown in vitro and in animal models to prevent platelet aggregation induced by platelet-activating factor and to stimulate vasodilation by increasing production of nitric oxide.^11,12

Furthermore, purified ginkgo extract might have beneficial effects on skin. A study in rats showed that when intraperitoneal ginkgo extract was given prior to radiation therapy, 100% of rats receiving placebo developed radiation dermatitis vs 13% of those that received ginkgo extract (P<.0001). An excisional skin biopsy showed a decrease in markers of oxidative stress in rats that received ginkgo extract prior to radiation.⁷

A randomized, double-blind clinical trial showed a significant reduction in disease progression in vitiligo patients assigned to receive ginkgo extract orally compared to placebo (P=.006).¹³ Research for many possible uses of ginkgo extract is ongoing.

Cutaneous Manifestations

Contact with the fruit of the ginkgo tree can induce allergic contact dermatitis,¹⁴ most often as erythematous papules, vesicles, and in some cases edema.^5,15

Exposures While Picking Berries—In 1939, Bolus¹⁵ reported the case of a patient who presented with edema, erythema, and vesicular lesions involving the hands and face after picking berries from a ginkgo tree. Later, patch testing on this patient, using ginkgo fruit, resulted in burning and stinging that necessitated removal of the patch, suggesting an irritant reaction. This was followed by a vesicular reaction that then developed within 24 hours, which was more consistent with allergy. Similarly, in 1988, a case series of contact dermatitis was reported in 3 patients after gathering ginkgo fruit.⁵

Incidental Exposure While Walking—In 1965, dermatitis broke out in 35 high school students, mainly affecting exposed portions of the leg, after ginkgo fruit fell and its pulp was exposed on a path at their school.⁴ Subsequently, patch testing was performed on 29 volunteers—some who had been exposed to ginkgo on that path, others without prior exposure. It was established that testing with ginkgo pulp directly caused an irritant reaction in all students, regardless of prior ginkgo exposure, but all prior ginkgo-exposed students in this study reacted positively to an acetone extract of ginkgo pulp and either poison ivy extract or pentadecylcatechol.⁴

Systemic Contact After Eating Fruit—An illustrative case of dermatitis, stomatitis, and proctitis was reported in a man with history of poison oak contact dermatitis who had eaten fruit from a ginkgo tree, suggesting systemic contact dermatitis. Weeks after resolution of symptoms, he reacted positively to ginkgo fruit and poison ivy extracts on patch testing.¹⁶

Ginkgo dermatitis tends to resolve upon removal of the inciting agent and application of a topical steroid.^8,17 Although many reported cases involve the fruit, allergic contact dermatitis can result from exposure to any part of the plant. In a reported case, a woman developed airborne contact dermatitis from working with sarcotesta of the ginkgo plant.¹⁸ Despite wearing rubber gloves, she broke out 1 week after exposure with erythema on the face and arms and severe facial edema.

Ginkgo leaves also can cause allergic contact dermatitis.¹⁹ Precautions should be taken when handling any component of the ginkgo tree.

Oral ginkgo supplementation has been implicated in a variety of other cutaneous reactions—from benign to life-threatening. When the ginkgo allergen concentration is too high within the supplement, as has been noted in some formulations, patients have presented with a diffuse morbilliform eruption within 1 or 2 weeks after taking ginkgo.²⁰ One patient—who was not taking any other medication—experienced an episode of acute generalized exanthematous pustulosis 48 hours after taking ginkgo.²¹ Ingestion of ginkgo extract also has been associated with Stevens-Johnson syndrome.^22-24

Other Adverse Reactions

The adverse effects of ginkgo supplement vary widely. In addition to dermatitis, ginkgo supplement can cause headaches, palpitations, tachycardia, vasculitis, nausea, and other symptoms.¹⁴

Metabolic Disturbance—One patient taking ginkgo who died after a seizure was found to have subtherapeutic levels of valproate and phenytoin,²⁵ which could be due to ginkgo’s effect on cytochrome p450 enzyme CYP2C19.²⁶ Ginkgo interactions with many cytochrome enzymes have been studied for potential drug interactions. Any other direct effects remain variable and controversial.^27,28

Hemorrhage—Another serious effect associated with taking ginkgo supplements is hemorrhage, often in conjunction with warfarin¹⁴; however, a meta-analysis indicated that ginkgo generally does not increase the risk of bleeding.²⁹ Other studies have shown that taking ginkgo with warfarin showed no difference in clotting status, and ginkgo with aspirin resulted in no clinically significant difference in bruising, bleeding, or platelet function in an analysis over a period of 1 month.^30,31 These findings notwithstanding, pregnant women, surgical patients, and those taking a blood thinner are advised as a general precaution not to take ginkgo extract.

Carcinogenesis—Ginkgo extract has antioxidant properties, but there is evidence that it might act as a carcinogen. An animal study reported by the US National Toxicology Program found that ginkgo induced mutagenic activity in the liver, thyroid, and nose of mice and rats. Over time, rodent liver underwent changes consistent with hepatic enzyme induction.³² More research is needed to clarify the role of ginkgo in this process.

Toxicity by Ingestion—Ginkgo seeds can cause food poisoning due to the compound 4’-O-methylpyridoxine (also known as ginkgotoxin).³³ Because methylpyridoxine can cause depletion of pyridoxal phosphate (a form of vitamin B₆ necessary for the synthesis of γ-aminobutyric acid), overconsumption of ginkgo seeds, even when fully cooked, might result in convulsions and even death.³³

Nomenclature and Distribution of Plants

Gingko biloba belongs to the Ginkgoaceae family (class Ginkgophytes). The tree originated in China but might no longer exist in a truly wild form. It is grown worldwide for its beauty and longevity. The female ginkgo tree is a gymnosperm, producing fruit with seeds that are not coated by an ovary wall¹⁵; male (nonfruiting) trees are preferentially planted because the fruit is surrounded by a pulp that, when dropped, emits a sour smell described variously as rancid butter, vomit, or excrement.⁵

Identifying Features and Plant Facts

The deciduous ginkgo tree has unique fan-shaped leaves and is cultivated for its beauty and resistance to disease (Figure 2).^4,34 It is nicknamed the maidenhair tree because the leaves are similar to the pinnae of the maidenhair fern.³⁴ Because G biloba is resistant to pollution, it often is planted along city streets.¹⁷ The leaf—5- to 8-cm wide and a symbol of the city of Tokyo, Japan³⁴—grows in clusters (Figure 3)⁵ and is green but turns yellow before it falls in autumn.³⁴ Leaf veins branch out into the blade without anastomosing.³⁴

Male flowers grow in a catkinlike pattern; female flowers grow on long stems.⁵ The fruit is small, dark, and shriveled, with a hint of silver⁴; it typically is 2 to 2.5 cm in diameter and contains the ginkgo nut or seed. The kernel of the ginkgo nut is edible when roasted and is used in traditional Chinese and Japanese cuisine as a dish served on special occasions in autumn.³³

Final Thoughts

Given that G biloba is a beautiful, commonly planted ornamental tree, gardeners and landscapers should be aware of the risk for allergic contact dermatitis and use proper protection. Dermatologists should be aware of its cross-reactivity with other common plants such as poison ivy and poison oak to help patients identify the cause of their reactions and avoid the inciting agent. Because ginkgo extract also can cause a cutaneous reaction or interact with other medications, providers should remember to take a thorough medication history that includes herbal medicines and supplements.

An ancient tree of the Ginkgoaceae family, Ginkgo biloba is known as a living fossil because its genome has been identified in fossils older than 200 million years.¹ An individual tree can live longer than 1000 years. Originating in China, G biloba (here, “ginkgo”) is cultivated worldwide for its attractive foliage (Figure 1). Ginkgo extract has long been used in traditional Chinese medicine; however, contact with the plant proper can provoke allergic contact dermatitis.

Dermatitis-Inducing Components

The allergenic component of the ginkgo tree is ginkgolic acid, which is structurally similar to urushiol and anacardic acid.^2,3 This compound can cause a cross-reaction in a person previously sensitized by contact with other plants. Urushiol is found in poison ivy(Toxicodendron radicans); anacardic acid is found in the cashew tree (Anacardium occidentale). Both plants belong to the family Anacardiaceae, commonly known as the cashew family.

Members of Anacardiaceae are the most common causes of plant-induced allergic contact dermatitis and include the cashew tree, mango tree, poison ivy, poison oak, and poison sumac. These plants can cross-react to cause contact dermatitis (Table).³ Patch tests have revealed that some individuals who are sensitive to components of the ginkgo tree also demonstrate sensitivity to poison ivy and poison sumac^4,5; countering this finding, Lepoittevin and colleagues⁶ demonstrated in animal studies that there was no cross-reactivity between ginkgo and urushiol, suggesting that patients with a reported cross-reaction might truly have been previously sensitized to both plants. In general, patients who have a history of a reaction to any Anacardiaceae plant should take precautions when handling them.

Therapeutic Benefit of Ginkgo

Ginkgo extract is sold as the herbal supplement EGB761, which acts as an antioxidant.⁷ In France, Germany, and China, it is a commonly prescribed herbal medicine.⁸ It is purported to support memory and attention; studies have shown improvement in cognition and in involvement with activities of daily living for patients with dementia.^9,10 Ginkgo extract might lessen peripheral vascular disease and cerebral circulatory disease, having been shown in vitro and in animal models to prevent platelet aggregation induced by platelet-activating factor and to stimulate vasodilation by increasing production of nitric oxide.^11,12

Furthermore, purified ginkgo extract might have beneficial effects on skin. A study in rats showed that when intraperitoneal ginkgo extract was given prior to radiation therapy, 100% of rats receiving placebo developed radiation dermatitis vs 13% of those that received ginkgo extract (P<.0001). An excisional skin biopsy showed a decrease in markers of oxidative stress in rats that received ginkgo extract prior to radiation.⁷

A randomized, double-blind clinical trial showed a significant reduction in disease progression in vitiligo patients assigned to receive ginkgo extract orally compared to placebo (P=.006).¹³ Research for many possible uses of ginkgo extract is ongoing.

Cutaneous Manifestations

Contact with the fruit of the ginkgo tree can induce allergic contact dermatitis,¹⁴ most often as erythematous papules, vesicles, and in some cases edema.^5,15

Exposures While Picking Berries—In 1939, Bolus¹⁵ reported the case of a patient who presented with edema, erythema, and vesicular lesions involving the hands and face after picking berries from a ginkgo tree. Later, patch testing on this patient, using ginkgo fruit, resulted in burning and stinging that necessitated removal of the patch, suggesting an irritant reaction. This was followed by a vesicular reaction that then developed within 24 hours, which was more consistent with allergy. Similarly, in 1988, a case series of contact dermatitis was reported in 3 patients after gathering ginkgo fruit.⁵

Incidental Exposure While Walking—In 1965, dermatitis broke out in 35 high school students, mainly affecting exposed portions of the leg, after ginkgo fruit fell and its pulp was exposed on a path at their school.⁴ Subsequently, patch testing was performed on 29 volunteers—some who had been exposed to ginkgo on that path, others without prior exposure. It was established that testing with ginkgo pulp directly caused an irritant reaction in all students, regardless of prior ginkgo exposure, but all prior ginkgo-exposed students in this study reacted positively to an acetone extract of ginkgo pulp and either poison ivy extract or pentadecylcatechol.⁴

Systemic Contact After Eating Fruit—An illustrative case of dermatitis, stomatitis, and proctitis was reported in a man with history of poison oak contact dermatitis who had eaten fruit from a ginkgo tree, suggesting systemic contact dermatitis. Weeks after resolution of symptoms, he reacted positively to ginkgo fruit and poison ivy extracts on patch testing.¹⁶

Ginkgo dermatitis tends to resolve upon removal of the inciting agent and application of a topical steroid.^8,17 Although many reported cases involve the fruit, allergic contact dermatitis can result from exposure to any part of the plant. In a reported case, a woman developed airborne contact dermatitis from working with sarcotesta of the ginkgo plant.¹⁸ Despite wearing rubber gloves, she broke out 1 week after exposure with erythema on the face and arms and severe facial edema.

Ginkgo leaves also can cause allergic contact dermatitis.¹⁹ Precautions should be taken when handling any component of the ginkgo tree.

Oral ginkgo supplementation has been implicated in a variety of other cutaneous reactions—from benign to life-threatening. When the ginkgo allergen concentration is too high within the supplement, as has been noted in some formulations, patients have presented with a diffuse morbilliform eruption within 1 or 2 weeks after taking ginkgo.²⁰ One patient—who was not taking any other medication—experienced an episode of acute generalized exanthematous pustulosis 48 hours after taking ginkgo.²¹ Ingestion of ginkgo extract also has been associated with Stevens-Johnson syndrome.^22-24

Other Adverse Reactions

The adverse effects of ginkgo supplement vary widely. In addition to dermatitis, ginkgo supplement can cause headaches, palpitations, tachycardia, vasculitis, nausea, and other symptoms.¹⁴

Metabolic Disturbance—One patient taking ginkgo who died after a seizure was found to have subtherapeutic levels of valproate and phenytoin,²⁵ which could be due to ginkgo’s effect on cytochrome p450 enzyme CYP2C19.²⁶ Ginkgo interactions with many cytochrome enzymes have been studied for potential drug interactions. Any other direct effects remain variable and controversial.^27,28

Hemorrhage—Another serious effect associated with taking ginkgo supplements is hemorrhage, often in conjunction with warfarin¹⁴; however, a meta-analysis indicated that ginkgo generally does not increase the risk of bleeding.²⁹ Other studies have shown that taking ginkgo with warfarin showed no difference in clotting status, and ginkgo with aspirin resulted in no clinically significant difference in bruising, bleeding, or platelet function in an analysis over a period of 1 month.^30,31 These findings notwithstanding, pregnant women, surgical patients, and those taking a blood thinner are advised as a general precaution not to take ginkgo extract.

Carcinogenesis—Ginkgo extract has antioxidant properties, but there is evidence that it might act as a carcinogen. An animal study reported by the US National Toxicology Program found that ginkgo induced mutagenic activity in the liver, thyroid, and nose of mice and rats. Over time, rodent liver underwent changes consistent with hepatic enzyme induction.³² More research is needed to clarify the role of ginkgo in this process.

Toxicity by Ingestion—Ginkgo seeds can cause food poisoning due to the compound 4’-O-methylpyridoxine (also known as ginkgotoxin).³³ Because methylpyridoxine can cause depletion of pyridoxal phosphate (a form of vitamin B₆ necessary for the synthesis of γ-aminobutyric acid), overconsumption of ginkgo seeds, even when fully cooked, might result in convulsions and even death.³³

Nomenclature and Distribution of Plants

Gingko biloba belongs to the Ginkgoaceae family (class Ginkgophytes). The tree originated in China but might no longer exist in a truly wild form. It is grown worldwide for its beauty and longevity. The female ginkgo tree is a gymnosperm, producing fruit with seeds that are not coated by an ovary wall¹⁵; male (nonfruiting) trees are preferentially planted because the fruit is surrounded by a pulp that, when dropped, emits a sour smell described variously as rancid butter, vomit, or excrement.⁵

Identifying Features and Plant Facts

The deciduous ginkgo tree has unique fan-shaped leaves and is cultivated for its beauty and resistance to disease (Figure 2).^4,34 It is nicknamed the maidenhair tree because the leaves are similar to the pinnae of the maidenhair fern.³⁴ Because G biloba is resistant to pollution, it often is planted along city streets.¹⁷ The leaf—5- to 8-cm wide and a symbol of the city of Tokyo, Japan³⁴—grows in clusters (Figure 3)⁵ and is green but turns yellow before it falls in autumn.³⁴ Leaf veins branch out into the blade without anastomosing.³⁴

Male flowers grow in a catkinlike pattern; female flowers grow on long stems.⁵ The fruit is small, dark, and shriveled, with a hint of silver⁴; it typically is 2 to 2.5 cm in diameter and contains the ginkgo nut or seed. The kernel of the ginkgo nut is edible when roasted and is used in traditional Chinese and Japanese cuisine as a dish served on special occasions in autumn.³³

Final Thoughts

Given that G biloba is a beautiful, commonly planted ornamental tree, gardeners and landscapers should be aware of the risk for allergic contact dermatitis and use proper protection. Dermatologists should be aware of its cross-reactivity with other common plants such as poison ivy and poison oak to help patients identify the cause of their reactions and avoid the inciting agent. Because ginkgo extract also can cause a cutaneous reaction or interact with other medications, providers should remember to take a thorough medication history that includes herbal medicines and supplements.

An ancient tree of the Ginkgoaceae family, Ginkgo biloba is known as a living fossil because its genome has been identified in fossils older than 200 million years.¹ An individual tree can live longer than 1000 years. Originating in China, G biloba (here, “ginkgo”) is cultivated worldwide for its attractive foliage (Figure 1). Ginkgo extract has long been used in traditional Chinese medicine; however, contact with the plant proper can provoke allergic contact dermatitis.

Dermatitis-Inducing Components

The allergenic component of the ginkgo tree is ginkgolic acid, which is structurally similar to urushiol and anacardic acid.^2,3 This compound can cause a cross-reaction in a person previously sensitized by contact with other plants. Urushiol is found in poison ivy(Toxicodendron radicans); anacardic acid is found in the cashew tree (Anacardium occidentale). Both plants belong to the family Anacardiaceae, commonly known as the cashew family.

Members of Anacardiaceae are the most common causes of plant-induced allergic contact dermatitis and include the cashew tree, mango tree, poison ivy, poison oak, and poison sumac. These plants can cross-react to cause contact dermatitis (Table).³ Patch tests have revealed that some individuals who are sensitive to components of the ginkgo tree also demonstrate sensitivity to poison ivy and poison sumac^4,5; countering this finding, Lepoittevin and colleagues⁶ demonstrated in animal studies that there was no cross-reactivity between ginkgo and urushiol, suggesting that patients with a reported cross-reaction might truly have been previously sensitized to both plants. In general, patients who have a history of a reaction to any Anacardiaceae plant should take precautions when handling them.

Therapeutic Benefit of Ginkgo

Ginkgo extract is sold as the herbal supplement EGB761, which acts as an antioxidant.⁷ In France, Germany, and China, it is a commonly prescribed herbal medicine.⁸ It is purported to support memory and attention; studies have shown improvement in cognition and in involvement with activities of daily living for patients with dementia.^9,10 Ginkgo extract might lessen peripheral vascular disease and cerebral circulatory disease, having been shown in vitro and in animal models to prevent platelet aggregation induced by platelet-activating factor and to stimulate vasodilation by increasing production of nitric oxide.^11,12

Furthermore, purified ginkgo extract might have beneficial effects on skin. A study in rats showed that when intraperitoneal ginkgo extract was given prior to radiation therapy, 100% of rats receiving placebo developed radiation dermatitis vs 13% of those that received ginkgo extract (P<.0001). An excisional skin biopsy showed a decrease in markers of oxidative stress in rats that received ginkgo extract prior to radiation.⁷

A randomized, double-blind clinical trial showed a significant reduction in disease progression in vitiligo patients assigned to receive ginkgo extract orally compared to placebo (P=.006).¹³ Research for many possible uses of ginkgo extract is ongoing.

Cutaneous Manifestations

Contact with the fruit of the ginkgo tree can induce allergic contact dermatitis,¹⁴ most often as erythematous papules, vesicles, and in some cases edema.^5,15

Exposures While Picking Berries—In 1939, Bolus¹⁵ reported the case of a patient who presented with edema, erythema, and vesicular lesions involving the hands and face after picking berries from a ginkgo tree. Later, patch testing on this patient, using ginkgo fruit, resulted in burning and stinging that necessitated removal of the patch, suggesting an irritant reaction. This was followed by a vesicular reaction that then developed within 24 hours, which was more consistent with allergy. Similarly, in 1988, a case series of contact dermatitis was reported in 3 patients after gathering ginkgo fruit.⁵

Incidental Exposure While Walking—In 1965, dermatitis broke out in 35 high school students, mainly affecting exposed portions of the leg, after ginkgo fruit fell and its pulp was exposed on a path at their school.⁴ Subsequently, patch testing was performed on 29 volunteers—some who had been exposed to ginkgo on that path, others without prior exposure. It was established that testing with ginkgo pulp directly caused an irritant reaction in all students, regardless of prior ginkgo exposure, but all prior ginkgo-exposed students in this study reacted positively to an acetone extract of ginkgo pulp and either poison ivy extract or pentadecylcatechol.⁴

Systemic Contact After Eating Fruit—An illustrative case of dermatitis, stomatitis, and proctitis was reported in a man with history of poison oak contact dermatitis who had eaten fruit from a ginkgo tree, suggesting systemic contact dermatitis. Weeks after resolution of symptoms, he reacted positively to ginkgo fruit and poison ivy extracts on patch testing.¹⁶

Ginkgo dermatitis tends to resolve upon removal of the inciting agent and application of a topical steroid.^8,17 Although many reported cases involve the fruit, allergic contact dermatitis can result from exposure to any part of the plant. In a reported case, a woman developed airborne contact dermatitis from working with sarcotesta of the ginkgo plant.¹⁸ Despite wearing rubber gloves, she broke out 1 week after exposure with erythema on the face and arms and severe facial edema.

Ginkgo leaves also can cause allergic contact dermatitis.¹⁹ Precautions should be taken when handling any component of the ginkgo tree.

Oral ginkgo supplementation has been implicated in a variety of other cutaneous reactions—from benign to life-threatening. When the ginkgo allergen concentration is too high within the supplement, as has been noted in some formulations, patients have presented with a diffuse morbilliform eruption within 1 or 2 weeks after taking ginkgo.²⁰ One patient—who was not taking any other medication—experienced an episode of acute generalized exanthematous pustulosis 48 hours after taking ginkgo.²¹ Ingestion of ginkgo extract also has been associated with Stevens-Johnson syndrome.^22-24

Other Adverse Reactions

The adverse effects of ginkgo supplement vary widely. In addition to dermatitis, ginkgo supplement can cause headaches, palpitations, tachycardia, vasculitis, nausea, and other symptoms.¹⁴

Metabolic Disturbance—One patient taking ginkgo who died after a seizure was found to have subtherapeutic levels of valproate and phenytoin,²⁵ which could be due to ginkgo’s effect on cytochrome p450 enzyme CYP2C19.²⁶ Ginkgo interactions with many cytochrome enzymes have been studied for potential drug interactions. Any other direct effects remain variable and controversial.^27,28

Hemorrhage—Another serious effect associated with taking ginkgo supplements is hemorrhage, often in conjunction with warfarin¹⁴; however, a meta-analysis indicated that ginkgo generally does not increase the risk of bleeding.²⁹ Other studies have shown that taking ginkgo with warfarin showed no difference in clotting status, and ginkgo with aspirin resulted in no clinically significant difference in bruising, bleeding, or platelet function in an analysis over a period of 1 month.^30,31 These findings notwithstanding, pregnant women, surgical patients, and those taking a blood thinner are advised as a general precaution not to take ginkgo extract.

Carcinogenesis—Ginkgo extract has antioxidant properties, but there is evidence that it might act as a carcinogen. An animal study reported by the US National Toxicology Program found that ginkgo induced mutagenic activity in the liver, thyroid, and nose of mice and rats. Over time, rodent liver underwent changes consistent with hepatic enzyme induction.³² More research is needed to clarify the role of ginkgo in this process.

Toxicity by Ingestion—Ginkgo seeds can cause food poisoning due to the compound 4’-O-methylpyridoxine (also known as ginkgotoxin).³³ Because methylpyridoxine can cause depletion of pyridoxal phosphate (a form of vitamin B₆ necessary for the synthesis of γ-aminobutyric acid), overconsumption of ginkgo seeds, even when fully cooked, might result in convulsions and even death.³³

Nomenclature and Distribution of Plants

Gingko biloba belongs to the Ginkgoaceae family (class Ginkgophytes). The tree originated in China but might no longer exist in a truly wild form. It is grown worldwide for its beauty and longevity. The female ginkgo tree is a gymnosperm, producing fruit with seeds that are not coated by an ovary wall¹⁵; male (nonfruiting) trees are preferentially planted because the fruit is surrounded by a pulp that, when dropped, emits a sour smell described variously as rancid butter, vomit, or excrement.⁵

Identifying Features and Plant Facts

The deciduous ginkgo tree has unique fan-shaped leaves and is cultivated for its beauty and resistance to disease (Figure 2).^4,34 It is nicknamed the maidenhair tree because the leaves are similar to the pinnae of the maidenhair fern.³⁴ Because G biloba is resistant to pollution, it often is planted along city streets.¹⁷ The leaf—5- to 8-cm wide and a symbol of the city of Tokyo, Japan³⁴—grows in clusters (Figure 3)⁵ and is green but turns yellow before it falls in autumn.³⁴ Leaf veins branch out into the blade without anastomosing.³⁴

Male flowers grow in a catkinlike pattern; female flowers grow on long stems.⁵ The fruit is small, dark, and shriveled, with a hint of silver⁴; it typically is 2 to 2.5 cm in diameter and contains the ginkgo nut or seed. The kernel of the ginkgo nut is edible when roasted and is used in traditional Chinese and Japanese cuisine as a dish served on special occasions in autumn.³³

Final Thoughts

Given that G biloba is a beautiful, commonly planted ornamental tree, gardeners and landscapers should be aware of the risk for allergic contact dermatitis and use proper protection. Dermatologists should be aware of its cross-reactivity with other common plants such as poison ivy and poison oak to help patients identify the cause of their reactions and avoid the inciting agent. Because ginkgo extract also can cause a cutaneous reaction or interact with other medications, providers should remember to take a thorough medication history that includes herbal medicines and supplements.

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.¹ But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.¹ However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.² Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.^3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.^1,6

First reported as a possible occupational allergen in 1944,⁷ aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response⁸; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.¹¹ Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,^12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.^14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.¹⁴ There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.¹⁵ Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.¹⁶

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.^17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.⁶ Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.^19,20

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.²¹ Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.²² With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.¹

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.^23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.²⁶ It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.^1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.¹ Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.^29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.^31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.³⁴ Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.¹ Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.²¹

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life^35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.^12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.^35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.^39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.¹⁴ In addition, patients may experience loss of sensitization to aluminum over time⁴¹; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.⁴² The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.⁶ On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.^36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.⁶

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.¹ Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.¹ But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.¹ However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.² Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.^3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.^1,6

First reported as a possible occupational allergen in 1944,⁷ aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response⁸; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.¹¹ Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,^12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.^14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.¹⁴ There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.¹⁵ Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.¹⁶

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.^17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.⁶ Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.^19,20

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.²¹ Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.²² With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.¹

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.^23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.²⁶ It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.^1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.¹ Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.^29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.^31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.³⁴ Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.¹ Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.²¹

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life^35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.^12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.^35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.^39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.¹⁴ In addition, patients may experience loss of sensitization to aluminum over time⁴¹; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.⁴² The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.⁶ On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.^36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.⁶

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.¹ Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.¹ But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.¹ However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.² Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.^3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.^1,6

First reported as a possible occupational allergen in 1944,⁷ aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response⁸; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.¹¹ Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,^12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.^14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.¹⁴ There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.¹⁵ Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.¹⁶

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.^17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.⁶ Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.^19,20

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.²¹ Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.²² With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.¹

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.^23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.²⁶ It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.^1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.¹ Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.^29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.^31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.³⁴ Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.¹ Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.²¹

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life^35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.^12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.^35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.^39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.¹⁴ In addition, patients may experience loss of sensitization to aluminum over time⁴¹; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.⁴² The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.⁶ On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.^36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.⁶

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.¹ Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

A patient presenting with a hand pustule is a phenomenon encountered worldwide requiring careful history-taking. Some occupations, activities, and various religious practices (eg, Eid al-Adha, Passover, Easter) have been implicated worldwide in orf infection. In the United States, orf virus usually is spread from infected animal hosts to humans. Herein, we review the differential for a single hand pustule, which includes both infectious and noninfectious causes. Recognizing orf virus as the etiology of a cutaneous hand pustule in patients is important, as misdiagnosis can lead to unnecessary invasive testing and/or treatments with suboptimal clinical outcomes.

Case Series

When conducting a search for orf virus cases at our institution (University of Iowa Hospitals and Clinics, Iowa City, Iowa), 5 patient cases were identified.

Patient 1—A 27-year-old otherwise healthy woman presented to clinic with a tender red bump on the right ring finger that had been slowly growing over the course of 2 weeks and had recently started to bleed. A social history revealed that she owned several goats, which she frequently milked; 1 of the goats had a cyst on the mouth, which she popped approximately 1 to 2 weeks prior to the appearance of the lesion on the finger. She also endorsed that she owned several cattle and various other animals with which she had frequent contact. A biopsy was obtained with features consistent with orf virus.

Patient 2—A 33-year-old man presented to clinic with a lesion of concern on the left index finger. Several days prior to presentation, the patient had visited the emergency department for swelling and erythema of the same finger after cutting himself with a knife while preparing sheep meat. Radiographs were normal, and the patient was referred to dermatology. In clinic, there was a 0.5-cm fluctuant mass on the distal interphalangeal joint of the third finger. The patient declined a biopsy, and the lesion healed over 4 to 6 weeks without complication.

Patient 3—A 38-year-old man presented to clinic with 2 painless, large, round nodules on the right proximal index finger, with open friable centers noted on physical examination (Figure 1). The patient reported cutting the finger while preparing sheep meat several days prior. The nodules had been present for a few weeks and continued to grow. A punch biopsy revealed evidence of parapoxvirus infection consistent with a diagnosis of orf.

Patient 4—A 48-year-old man was referred to our dermatology clinic for evaluation of a bleeding lesion on the left middle finger. Physical examination revealed an exophytic, friable, ulcerated nodule on the dorsal aspect of the left middle finger (Figure 2). Upon further questioning, the patient mentioned that he handled raw lamb meat after cutting the finger. A punch biopsy was obtained and was consistent with orf virus infection.

Patient 5—A 43-year-old woman presented to clinic with a chronic wound on the mid lower back that was noted to drain and crust over. She thought the lesion was improving, but it had become painful over the last few weeks. A shave biopsy of the lesion was consistent with orf virus. At follow-up, the patient was unable to identify any recent contact with animals.

Transmission From Animals to Humans—Orf virus is a member of the Parapoxvirus genus of the Poxviridae family.¹ This virus is highly contagious among animals and has been described around the globe. The resulting disease also is known as contagious pustular dermatitis,² soremuzzle,³ ecthyma contagiosum of sheep,⁴ and scabby mouth.⁵ This virus most commonly infects young lambs and manifests as raw to crusty papules, pustules, or vesicles around the mouth and nose of the animal.⁴ Additional signs include excessive salivation and weight loss or starvation from the inability to suckle because of the lesions.⁵ Although ecthyma contagiosum infection of sheep and goats has been well known for centuries, human infection was first reported in the literature in 1934.⁶

Transmission of orf to humans can occur when direct contact with an infected animal exhibiting active lesions occurs.⁷ Orf virus also can be transmitted through fomites (eg, from knives, wool, buildings, equipment) that previously were in contact with infected animals, making it relevant to ask all farmers about any animals with pustules around the mouth, nose, udders, or other commonly affected areas. Although sanitation efforts are important for prevention, orf virus is hardy, and fomites can remain on surfaces for many months.⁸ Transmission among animals and from animals to humans frequently occurs; however, human-to-human transmission is less common.⁹ Ecthyma contagiosum is considered an occupational hazard, with the disease being most prevalent in shepherds, veterinarians, and butchers.^1,8 Disease prevalence in these occupations has been reported to be as high as 50%.¹⁰ Infections also are seen in patients who attend petting zoos or who slaughter goats and sheep for cultural practices.⁸

Clinical Characteristics in Humans—The clinical diagnosis of orf is dependent on taking a thorough patient history that includes social, occupational, and religious activities. Development of a nodule or papule on a patient’s hand with recent exposure to fomites or direct contact with a goat or sheep up to 1 week prior is extremely suggestive of an orf virus infection.

Clinically, orf most often begins as an individual papule or nodule on the dorsal surface of the patient’s finger or hand and ranges from completely asymptomatic to pruritic or even painful.^1,8 Depending on how the infection was inoculated, lesions can vary in size and number. Other sites that have been reported less frequently include the genitals, legs, axillae, and head.^11,12 Lesions are roughly 1 cm in diameter but can vary in size. Ecthyma contagiosum is not a static disease but changes in appearance over the course of infection. Typically, lesions will appear 3 to 7 days after inoculation with the orf virus and will self-resolve 6 to 8 weeks later.

Orf lesions have been described to progress through 6 distinct phases before resolving: maculopapular (erythematous macule or papule forms), targetoid (formation of a necrotic center with red outer halo), acute (lesion begins to weep), regenerative (lesion becomes dry), papilloma (dry crust becomes papillomatous), and regression (skin returns to normal appearance).^1,8,9 Each phase of ecthyma contagiosum is unique and will last up to 1 week before progressing. Because of this prolonged clinical course, patients can present at any stage.

Reports of systemic symptoms are uncommon but can include lymphadenopathy, fever, and malaise.¹³ Although the disease course in immunocompetent individuals is quite mild, immunocompromised patients may experience persistent orf lesions that are painful and can be much larger, with reports of several centimeters in diameter.¹⁴

Dermatopathology and Molecular Studies—When a clinical diagnosis is not possible, biopsy or molecular studies can be helpful.⁸ Histopathology can vary depending on the phase of the lesion. Early stages are characterized by spongiform degeneration of the epidermis with variable vesiculation of the superficial epidermis and eosinophilic cytoplasmic inclusion bodies of keratinocytes (Figure 3). Later stages demonstrate full-thickness necrosis with epidermal balloon degeneration and dense inflammation of the dermis with edema and extravasated erythrocytes from dilated blood vessels. Both early- and late-stage disease commonly show characteristic elongated thin rete ridges.⁸

Molecular studies are another reliable method for diagnosis, though these are not always readily available. Polymerase chain reaction can be used for sensitive and rapid diagnosis.¹⁵ Less commonly, electron microscopy, Western blot, or enzyme-linked immunosorbent assays are used.¹⁶ Laboratory studies, such as complete blood cell count with differential, erythrocyte sedimentation rate, and C-reactive protein, often are unnecessary but may be helpful in ruling out other infectious causes. Tissue culture can be considered if bacterial, fungal, or acid-fast bacilli are in the differential; however, no growth will be seen in the case of orf viral infection.

Differential Diagnosis—The differential diagnosis for patients presenting with a large pustule on the hand or fingers can depend on geographic location, as the potential etiology may vary widely around the world. Several zoonotic viral infections other than orf can present with pustular lesions on the hands (Table).^17-24

Clinically, infection with these named viruses can be hard to distinguish; however, appropriate social history or polymerase chain reaction can be obtained to differentiate them. Other infectious entities include herpetic whitlow, giant molluscum, and anthrax (eTable).^24-26 Biopsy of the lesion with bacterial tissue culture may lead to definitive diagnosis.²⁶

Treatment—Because of the self-resolving nature of orf, treatment usually is not needed in immunocompetent patients with a solitary lesion. However, wound care is essential to prevent secondary infections of the lesion. If secondarily infected, topical or oral antibiotics may be prescribed. Immunocompromised individuals are at increased risk for developing large persistent lesions and sometimes require intervention for successful treatment. Several successful treatment methods have been described and include intralesional interferon injections, electrocautery, topical imiquimod, topical cidofovir, and cryotherapy.^8,14,27-30 Infections that continue to be refractory to less-invasive treatment can be considered for wide local excision; however, recurrence is possible.⁸ Vaccinations are available for animals to prevent the spread of infection in the flock, but there are no formulations of vaccines for human use. Prevention of spread to humans can be done through animal vaccination, careful handling of animal products while wearing nonporous gloves, and proper sanitation techniques.

Complications—Orf has an excellent long-term prognosis in immunocompetent patients, as the virus is epitheliotropic, and inoculation does not lead to viremia.² Although lesions typically are asymptomatic in most patients, complications can occur, especially in immunosuppressed individuals. These complications include systemic symptoms, giant persistent lesions prone to infection or scarring, erysipelas, lymphadenitis, and erythema multiforme.^8,31 Common systemic symptoms of ecthyma contagiosum include fever, fatigue, and myalgia. Lymphadenitis can occur along with local swelling and lymphatic streaking. Although erythema multiforme is a rare complication occurring after initial ecthyma contagiosum infection, this hypersensitivity reaction is postulated to be in response to the immunologic clearing of the orf virus.^32,33 Patients receiving systemic immunosuppressive medications are at an increased risk of developing complications from infection and may even be required to pause systemic treatment for complete resolution of orf lesions.³⁴ Other cutaneous diseases that decrease the skin’s barrier protection, such as bullous pemphigoid or eczema, also can place patients at an increased risk for complications.³⁵ Although human-to-human orf virus transmission is exceptionally rare, there is a case report of this phenomenon in immunosuppressed patients residing in a burn unit.³⁶ Transplant recipients on immunosuppressive medications also can experience orf lesions with exaggerated presentations that continue to grow up to several centimeters in diameter.³¹ Long-term prognosis is still good in these patients with appropriate disease recognition and treatment. Reinfection is not uncommon with repeated exposure to the source, but lesions are less severe and resolve faster than with initial infection.^1,8

Conclusion

The contagious hand pustule caused by orf virus is a distinct clinical entity that is prevalent worldwide and requires thorough evaluation of the clinical course of the lesion and the patient’s social history. Several zoonotic viral infections have been implicated in this presentation. Although biopsy and molecular studies can be helpful, the expert diagnostician can make a clinical diagnosis with careful attention to social history, geographic location, and cultural practices.

A patient presenting with a hand pustule is a phenomenon encountered worldwide requiring careful history-taking. Some occupations, activities, and various religious practices (eg, Eid al-Adha, Passover, Easter) have been implicated worldwide in orf infection. In the United States, orf virus usually is spread from infected animal hosts to humans. Herein, we review the differential for a single hand pustule, which includes both infectious and noninfectious causes. Recognizing orf virus as the etiology of a cutaneous hand pustule in patients is important, as misdiagnosis can lead to unnecessary invasive testing and/or treatments with suboptimal clinical outcomes.

Case Series

When conducting a search for orf virus cases at our institution (University of Iowa Hospitals and Clinics, Iowa City, Iowa), 5 patient cases were identified.

Patient 1—A 27-year-old otherwise healthy woman presented to clinic with a tender red bump on the right ring finger that had been slowly growing over the course of 2 weeks and had recently started to bleed. A social history revealed that she owned several goats, which she frequently milked; 1 of the goats had a cyst on the mouth, which she popped approximately 1 to 2 weeks prior to the appearance of the lesion on the finger. She also endorsed that she owned several cattle and various other animals with which she had frequent contact. A biopsy was obtained with features consistent with orf virus.

Patient 2—A 33-year-old man presented to clinic with a lesion of concern on the left index finger. Several days prior to presentation, the patient had visited the emergency department for swelling and erythema of the same finger after cutting himself with a knife while preparing sheep meat. Radiographs were normal, and the patient was referred to dermatology. In clinic, there was a 0.5-cm fluctuant mass on the distal interphalangeal joint of the third finger. The patient declined a biopsy, and the lesion healed over 4 to 6 weeks without complication.

Patient 3—A 38-year-old man presented to clinic with 2 painless, large, round nodules on the right proximal index finger, with open friable centers noted on physical examination (Figure 1). The patient reported cutting the finger while preparing sheep meat several days prior. The nodules had been present for a few weeks and continued to grow. A punch biopsy revealed evidence of parapoxvirus infection consistent with a diagnosis of orf.

Patient 4—A 48-year-old man was referred to our dermatology clinic for evaluation of a bleeding lesion on the left middle finger. Physical examination revealed an exophytic, friable, ulcerated nodule on the dorsal aspect of the left middle finger (Figure 2). Upon further questioning, the patient mentioned that he handled raw lamb meat after cutting the finger. A punch biopsy was obtained and was consistent with orf virus infection.

Patient 5—A 43-year-old woman presented to clinic with a chronic wound on the mid lower back that was noted to drain and crust over. She thought the lesion was improving, but it had become painful over the last few weeks. A shave biopsy of the lesion was consistent with orf virus. At follow-up, the patient was unable to identify any recent contact with animals.

Transmission From Animals to Humans—Orf virus is a member of the Parapoxvirus genus of the Poxviridae family.¹ This virus is highly contagious among animals and has been described around the globe. The resulting disease also is known as contagious pustular dermatitis,² soremuzzle,³ ecthyma contagiosum of sheep,⁴ and scabby mouth.⁵ This virus most commonly infects young lambs and manifests as raw to crusty papules, pustules, or vesicles around the mouth and nose of the animal.⁴ Additional signs include excessive salivation and weight loss or starvation from the inability to suckle because of the lesions.⁵ Although ecthyma contagiosum infection of sheep and goats has been well known for centuries, human infection was first reported in the literature in 1934.⁶

Transmission of orf to humans can occur when direct contact with an infected animal exhibiting active lesions occurs.⁷ Orf virus also can be transmitted through fomites (eg, from knives, wool, buildings, equipment) that previously were in contact with infected animals, making it relevant to ask all farmers about any animals with pustules around the mouth, nose, udders, or other commonly affected areas. Although sanitation efforts are important for prevention, orf virus is hardy, and fomites can remain on surfaces for many months.⁸ Transmission among animals and from animals to humans frequently occurs; however, human-to-human transmission is less common.⁹ Ecthyma contagiosum is considered an occupational hazard, with the disease being most prevalent in shepherds, veterinarians, and butchers.^1,8 Disease prevalence in these occupations has been reported to be as high as 50%.¹⁰ Infections also are seen in patients who attend petting zoos or who slaughter goats and sheep for cultural practices.⁸

Clinical Characteristics in Humans—The clinical diagnosis of orf is dependent on taking a thorough patient history that includes social, occupational, and religious activities. Development of a nodule or papule on a patient’s hand with recent exposure to fomites or direct contact with a goat or sheep up to 1 week prior is extremely suggestive of an orf virus infection.

Clinically, orf most often begins as an individual papule or nodule on the dorsal surface of the patient’s finger or hand and ranges from completely asymptomatic to pruritic or even painful.^1,8 Depending on how the infection was inoculated, lesions can vary in size and number. Other sites that have been reported less frequently include the genitals, legs, axillae, and head.^11,12 Lesions are roughly 1 cm in diameter but can vary in size. Ecthyma contagiosum is not a static disease but changes in appearance over the course of infection. Typically, lesions will appear 3 to 7 days after inoculation with the orf virus and will self-resolve 6 to 8 weeks later.

Orf lesions have been described to progress through 6 distinct phases before resolving: maculopapular (erythematous macule or papule forms), targetoid (formation of a necrotic center with red outer halo), acute (lesion begins to weep), regenerative (lesion becomes dry), papilloma (dry crust becomes papillomatous), and regression (skin returns to normal appearance).^1,8,9 Each phase of ecthyma contagiosum is unique and will last up to 1 week before progressing. Because of this prolonged clinical course, patients can present at any stage.

Reports of systemic symptoms are uncommon but can include lymphadenopathy, fever, and malaise.¹³ Although the disease course in immunocompetent individuals is quite mild, immunocompromised patients may experience persistent orf lesions that are painful and can be much larger, with reports of several centimeters in diameter.¹⁴

Dermatopathology and Molecular Studies—When a clinical diagnosis is not possible, biopsy or molecular studies can be helpful.⁸ Histopathology can vary depending on the phase of the lesion. Early stages are characterized by spongiform degeneration of the epidermis with variable vesiculation of the superficial epidermis and eosinophilic cytoplasmic inclusion bodies of keratinocytes (Figure 3). Later stages demonstrate full-thickness necrosis with epidermal balloon degeneration and dense inflammation of the dermis with edema and extravasated erythrocytes from dilated blood vessels. Both early- and late-stage disease commonly show characteristic elongated thin rete ridges.⁸

Molecular studies are another reliable method for diagnosis, though these are not always readily available. Polymerase chain reaction can be used for sensitive and rapid diagnosis.¹⁵ Less commonly, electron microscopy, Western blot, or enzyme-linked immunosorbent assays are used.¹⁶ Laboratory studies, such as complete blood cell count with differential, erythrocyte sedimentation rate, and C-reactive protein, often are unnecessary but may be helpful in ruling out other infectious causes. Tissue culture can be considered if bacterial, fungal, or acid-fast bacilli are in the differential; however, no growth will be seen in the case of orf viral infection.

Differential Diagnosis—The differential diagnosis for patients presenting with a large pustule on the hand or fingers can depend on geographic location, as the potential etiology may vary widely around the world. Several zoonotic viral infections other than orf can present with pustular lesions on the hands (Table).^17-24

Clinically, infection with these named viruses can be hard to distinguish; however, appropriate social history or polymerase chain reaction can be obtained to differentiate them. Other infectious entities include herpetic whitlow, giant molluscum, and anthrax (eTable).^24-26 Biopsy of the lesion with bacterial tissue culture may lead to definitive diagnosis.²⁶

Treatment—Because of the self-resolving nature of orf, treatment usually is not needed in immunocompetent patients with a solitary lesion. However, wound care is essential to prevent secondary infections of the lesion. If secondarily infected, topical or oral antibiotics may be prescribed. Immunocompromised individuals are at increased risk for developing large persistent lesions and sometimes require intervention for successful treatment. Several successful treatment methods have been described and include intralesional interferon injections, electrocautery, topical imiquimod, topical cidofovir, and cryotherapy.^8,14,27-30 Infections that continue to be refractory to less-invasive treatment can be considered for wide local excision; however, recurrence is possible.⁸ Vaccinations are available for animals to prevent the spread of infection in the flock, but there are no formulations of vaccines for human use. Prevention of spread to humans can be done through animal vaccination, careful handling of animal products while wearing nonporous gloves, and proper sanitation techniques.

Complications—Orf has an excellent long-term prognosis in immunocompetent patients, as the virus is epitheliotropic, and inoculation does not lead to viremia.² Although lesions typically are asymptomatic in most patients, complications can occur, especially in immunosuppressed individuals. These complications include systemic symptoms, giant persistent lesions prone to infection or scarring, erysipelas, lymphadenitis, and erythema multiforme.^8,31 Common systemic symptoms of ecthyma contagiosum include fever, fatigue, and myalgia. Lymphadenitis can occur along with local swelling and lymphatic streaking. Although erythema multiforme is a rare complication occurring after initial ecthyma contagiosum infection, this hypersensitivity reaction is postulated to be in response to the immunologic clearing of the orf virus.^32,33 Patients receiving systemic immunosuppressive medications are at an increased risk of developing complications from infection and may even be required to pause systemic treatment for complete resolution of orf lesions.³⁴ Other cutaneous diseases that decrease the skin’s barrier protection, such as bullous pemphigoid or eczema, also can place patients at an increased risk for complications.³⁵ Although human-to-human orf virus transmission is exceptionally rare, there is a case report of this phenomenon in immunosuppressed patients residing in a burn unit.³⁶ Transplant recipients on immunosuppressive medications also can experience orf lesions with exaggerated presentations that continue to grow up to several centimeters in diameter.³¹ Long-term prognosis is still good in these patients with appropriate disease recognition and treatment. Reinfection is not uncommon with repeated exposure to the source, but lesions are less severe and resolve faster than with initial infection.^1,8

Conclusion

The contagious hand pustule caused by orf virus is a distinct clinical entity that is prevalent worldwide and requires thorough evaluation of the clinical course of the lesion and the patient’s social history. Several zoonotic viral infections have been implicated in this presentation. Although biopsy and molecular studies can be helpful, the expert diagnostician can make a clinical diagnosis with careful attention to social history, geographic location, and cultural practices.

A patient presenting with a hand pustule is a phenomenon encountered worldwide requiring careful history-taking. Some occupations, activities, and various religious practices (eg, Eid al-Adha, Passover, Easter) have been implicated worldwide in orf infection. In the United States, orf virus usually is spread from infected animal hosts to humans. Herein, we review the differential for a single hand pustule, which includes both infectious and noninfectious causes. Recognizing orf virus as the etiology of a cutaneous hand pustule in patients is important, as misdiagnosis can lead to unnecessary invasive testing and/or treatments with suboptimal clinical outcomes.

Case Series

When conducting a search for orf virus cases at our institution (University of Iowa Hospitals and Clinics, Iowa City, Iowa), 5 patient cases were identified.

Patient 1—A 27-year-old otherwise healthy woman presented to clinic with a tender red bump on the right ring finger that had been slowly growing over the course of 2 weeks and had recently started to bleed. A social history revealed that she owned several goats, which she frequently milked; 1 of the goats had a cyst on the mouth, which she popped approximately 1 to 2 weeks prior to the appearance of the lesion on the finger. She also endorsed that she owned several cattle and various other animals with which she had frequent contact. A biopsy was obtained with features consistent with orf virus.

Patient 2—A 33-year-old man presented to clinic with a lesion of concern on the left index finger. Several days prior to presentation, the patient had visited the emergency department for swelling and erythema of the same finger after cutting himself with a knife while preparing sheep meat. Radiographs were normal, and the patient was referred to dermatology. In clinic, there was a 0.5-cm fluctuant mass on the distal interphalangeal joint of the third finger. The patient declined a biopsy, and the lesion healed over 4 to 6 weeks without complication.

Patient 3—A 38-year-old man presented to clinic with 2 painless, large, round nodules on the right proximal index finger, with open friable centers noted on physical examination (Figure 1). The patient reported cutting the finger while preparing sheep meat several days prior. The nodules had been present for a few weeks and continued to grow. A punch biopsy revealed evidence of parapoxvirus infection consistent with a diagnosis of orf.

Patient 4—A 48-year-old man was referred to our dermatology clinic for evaluation of a bleeding lesion on the left middle finger. Physical examination revealed an exophytic, friable, ulcerated nodule on the dorsal aspect of the left middle finger (Figure 2). Upon further questioning, the patient mentioned that he handled raw lamb meat after cutting the finger. A punch biopsy was obtained and was consistent with orf virus infection.

Patient 5—A 43-year-old woman presented to clinic with a chronic wound on the mid lower back that was noted to drain and crust over. She thought the lesion was improving, but it had become painful over the last few weeks. A shave biopsy of the lesion was consistent with orf virus. At follow-up, the patient was unable to identify any recent contact with animals.

Transmission From Animals to Humans—Orf virus is a member of the Parapoxvirus genus of the Poxviridae family.¹ This virus is highly contagious among animals and has been described around the globe. The resulting disease also is known as contagious pustular dermatitis,² soremuzzle,³ ecthyma contagiosum of sheep,⁴ and scabby mouth.⁵ This virus most commonly infects young lambs and manifests as raw to crusty papules, pustules, or vesicles around the mouth and nose of the animal.⁴ Additional signs include excessive salivation and weight loss or starvation from the inability to suckle because of the lesions.⁵ Although ecthyma contagiosum infection of sheep and goats has been well known for centuries, human infection was first reported in the literature in 1934.⁶

Transmission of orf to humans can occur when direct contact with an infected animal exhibiting active lesions occurs.⁷ Orf virus also can be transmitted through fomites (eg, from knives, wool, buildings, equipment) that previously were in contact with infected animals, making it relevant to ask all farmers about any animals with pustules around the mouth, nose, udders, or other commonly affected areas. Although sanitation efforts are important for prevention, orf virus is hardy, and fomites can remain on surfaces for many months.⁸ Transmission among animals and from animals to humans frequently occurs; however, human-to-human transmission is less common.⁹ Ecthyma contagiosum is considered an occupational hazard, with the disease being most prevalent in shepherds, veterinarians, and butchers.^1,8 Disease prevalence in these occupations has been reported to be as high as 50%.¹⁰ Infections also are seen in patients who attend petting zoos or who slaughter goats and sheep for cultural practices.⁸

Clinical Characteristics in Humans—The clinical diagnosis of orf is dependent on taking a thorough patient history that includes social, occupational, and religious activities. Development of a nodule or papule on a patient’s hand with recent exposure to fomites or direct contact with a goat or sheep up to 1 week prior is extremely suggestive of an orf virus infection.

Clinically, orf most often begins as an individual papule or nodule on the dorsal surface of the patient’s finger or hand and ranges from completely asymptomatic to pruritic or even painful.^1,8 Depending on how the infection was inoculated, lesions can vary in size and number. Other sites that have been reported less frequently include the genitals, legs, axillae, and head.^11,12 Lesions are roughly 1 cm in diameter but can vary in size. Ecthyma contagiosum is not a static disease but changes in appearance over the course of infection. Typically, lesions will appear 3 to 7 days after inoculation with the orf virus and will self-resolve 6 to 8 weeks later.

Orf lesions have been described to progress through 6 distinct phases before resolving: maculopapular (erythematous macule or papule forms), targetoid (formation of a necrotic center with red outer halo), acute (lesion begins to weep), regenerative (lesion becomes dry), papilloma (dry crust becomes papillomatous), and regression (skin returns to normal appearance).^1,8,9 Each phase of ecthyma contagiosum is unique and will last up to 1 week before progressing. Because of this prolonged clinical course, patients can present at any stage.

Reports of systemic symptoms are uncommon but can include lymphadenopathy, fever, and malaise.¹³ Although the disease course in immunocompetent individuals is quite mild, immunocompromised patients may experience persistent orf lesions that are painful and can be much larger, with reports of several centimeters in diameter.¹⁴

Dermatopathology and Molecular Studies—When a clinical diagnosis is not possible, biopsy or molecular studies can be helpful.⁸ Histopathology can vary depending on the phase of the lesion. Early stages are characterized by spongiform degeneration of the epidermis with variable vesiculation of the superficial epidermis and eosinophilic cytoplasmic inclusion bodies of keratinocytes (Figure 3). Later stages demonstrate full-thickness necrosis with epidermal balloon degeneration and dense inflammation of the dermis with edema and extravasated erythrocytes from dilated blood vessels. Both early- and late-stage disease commonly show characteristic elongated thin rete ridges.⁸

Molecular studies are another reliable method for diagnosis, though these are not always readily available. Polymerase chain reaction can be used for sensitive and rapid diagnosis.¹⁵ Less commonly, electron microscopy, Western blot, or enzyme-linked immunosorbent assays are used.¹⁶ Laboratory studies, such as complete blood cell count with differential, erythrocyte sedimentation rate, and C-reactive protein, often are unnecessary but may be helpful in ruling out other infectious causes. Tissue culture can be considered if bacterial, fungal, or acid-fast bacilli are in the differential; however, no growth will be seen in the case of orf viral infection.

Differential Diagnosis—The differential diagnosis for patients presenting with a large pustule on the hand or fingers can depend on geographic location, as the potential etiology may vary widely around the world. Several zoonotic viral infections other than orf can present with pustular lesions on the hands (Table).^17-24

Clinically, infection with these named viruses can be hard to distinguish; however, appropriate social history or polymerase chain reaction can be obtained to differentiate them. Other infectious entities include herpetic whitlow, giant molluscum, and anthrax (eTable).^24-26 Biopsy of the lesion with bacterial tissue culture may lead to definitive diagnosis.²⁶

Treatment—Because of the self-resolving nature of orf, treatment usually is not needed in immunocompetent patients with a solitary lesion. However, wound care is essential to prevent secondary infections of the lesion. If secondarily infected, topical or oral antibiotics may be prescribed. Immunocompromised individuals are at increased risk for developing large persistent lesions and sometimes require intervention for successful treatment. Several successful treatment methods have been described and include intralesional interferon injections, electrocautery, topical imiquimod, topical cidofovir, and cryotherapy.^8,14,27-30 Infections that continue to be refractory to less-invasive treatment can be considered for wide local excision; however, recurrence is possible.⁸ Vaccinations are available for animals to prevent the spread of infection in the flock, but there are no formulations of vaccines for human use. Prevention of spread to humans can be done through animal vaccination, careful handling of animal products while wearing nonporous gloves, and proper sanitation techniques.

Complications—Orf has an excellent long-term prognosis in immunocompetent patients, as the virus is epitheliotropic, and inoculation does not lead to viremia.² Although lesions typically are asymptomatic in most patients, complications can occur, especially in immunosuppressed individuals. These complications include systemic symptoms, giant persistent lesions prone to infection or scarring, erysipelas, lymphadenitis, and erythema multiforme.^8,31 Common systemic symptoms of ecthyma contagiosum include fever, fatigue, and myalgia. Lymphadenitis can occur along with local swelling and lymphatic streaking. Although erythema multiforme is a rare complication occurring after initial ecthyma contagiosum infection, this hypersensitivity reaction is postulated to be in response to the immunologic clearing of the orf virus.^32,33 Patients receiving systemic immunosuppressive medications are at an increased risk of developing complications from infection and may even be required to pause systemic treatment for complete resolution of orf lesions.³⁴ Other cutaneous diseases that decrease the skin’s barrier protection, such as bullous pemphigoid or eczema, also can place patients at an increased risk for complications.³⁵ Although human-to-human orf virus transmission is exceptionally rare, there is a case report of this phenomenon in immunosuppressed patients residing in a burn unit.³⁶ Transplant recipients on immunosuppressive medications also can experience orf lesions with exaggerated presentations that continue to grow up to several centimeters in diameter.³¹ Long-term prognosis is still good in these patients with appropriate disease recognition and treatment. Reinfection is not uncommon with repeated exposure to the source, but lesions are less severe and resolve faster than with initial infection.^1,8

Conclusion

The contagious hand pustule caused by orf virus is a distinct clinical entity that is prevalent worldwide and requires thorough evaluation of the clinical course of the lesion and the patient’s social history. Several zoonotic viral infections have been implicated in this presentation. Although biopsy and molecular studies can be helpful, the expert diagnostician can make a clinical diagnosis with careful attention to social history, geographic location, and cultural practices.

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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

World Health Organization officials announced July 6 that they’re tracking a new subvariant of Omicron, which is becoming more common in India.

The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.

“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.

The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.

“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.

The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.

Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.

BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.

Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.

The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.

BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.

“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.

“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.

Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.

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

World Health Organization officials announced July 6 that they’re tracking a new subvariant of Omicron, which is becoming more common in India.

The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.

“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.

The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.

“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.

The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.

Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.

BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.

Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.

The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.

BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.

“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.

“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.

Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.

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

World Health Organization officials announced July 6 that they’re tracking a new subvariant of Omicron, which is becoming more common in India.

The subvariant, a sublineage of BA.2 being called BA.2.75, has been reported in eight countries and hasn’t yet been declared a variant of concern.

“There’s been an emergence of a ‘could be’ subvariant. It’s been not yet officially called, but some people are referring to it as BA.2.75,” Soumya Swaminathan, MD, the WHO’s chief scientist, said in a video posted on Twitter.

The subvariant appears to have mutations similar to other contagious strains, she said, though there are a limited number of sequences available to analyze. How transmissible and severe it is, and how well it can evade our immunity, aren’t yet known.

“We have to wait and see, and of course, we are tracking it,” Dr. Swaminathan said.

The WHO committee responsible for analyzing global coronavirus data will label the subvariant officially and release more information as the situation warrants it, she said.

Public health experts around the world are also talking about the subvariant, which has been nicknamed Centaurus. BA.2.75 was first found in India in May and is now competing with BA.5, which has become dominant in the United States.

BA.2.75 has eight mutations beyond those seen in BA.5, which “could make immune escape worse than what we’re seeing now,” Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief at Medscape, wrote in a Twitter post.

Individually, the extra mutations aren’t too concerning, “but all appearing together at once is another matter,” Tom Peacock, PhD, a virologist at Imperial College London, wrote in a Twitter post.

The “apparent rapid growth and wide geographical spread” are “worth keeping a close eye on,” he said.

BA.2.75 has been found in a handful of cases in the United States, Australia, Canada, Germany, Japan, New Zealand, and the United Kingdom. In India, the sequence accounts for about 23% of recent samples.

“It is really too early to know if BA.2.75 will take over relative to BA.2 or even relative to BA.5,” Ulrich Elling, PhD, a researcher at Australia’s Institute of Molecular Biotechnology, wrote in a Twitter post.

“Just to emphasize it again: While the distribution across Indian regions as well as internationally and the very rapid appearance makes it likely we are dealing with a variant spreading fast and spread widely already, the absolute data points are few,” he said.

Globally, coronavirus cases have increased nearly 30% during the past 2 weeks, the WHO said July 6. Four out of six of the WHO subregions reported an increase in the last week, with BA.4 and BA.5 driving waves in the United States and Europe.

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

Among 1,065 adults with atopic dermatitis (AD) who were surveyed about their condition, no single element of disease burden, including sleep, stood out as having a strong association with overall disease burden. However, AD severity and spending 11 hours or more per week managing the condition did correlate with higher overall disease burden.

“Research has documented the disease burden of AD, including its visible nature and the effect on itch and sleep, but knowledge gaps remain,” Aaron M. Drucker, MD, of the division of dermatology at the University of Toronto, and colleagues wrote in the study published online in JAMA Dermatology. “Gaps include a poor understanding of symptoms other than itch, patients’ treatment experience, and how different elements of burden of disease interact.”

©aniaostudio/Thinkstock.com

Dr. Drucker and colleagues collected data from an externally led patient-focused drug development survey on AD, a 32-item questionnaire that was administered electronically between Aug. 1, 2019, and Oct. 11, 2019. Respondents were asked to rate the overall impact of their AD in the past months and the specific elements of disease burden on a 1-5 scale, with 1 meaning no impact, and 5 meaning a significant impact. They were also asked to rate current mood changes and mood changes at the worst point of AD on a 4-point scale that ranged from “not present” to “severe.” The researchers used multivariable ordinal regression to examine associations between demographic and clinical variables and patient-reported overall AD impact scores.
 

Survey results

Of the 1,065 respondents, 33% were aged 18-34 years, 50% were aged 35-50 years, 17% were aged 65 years or older, and 83% were female. Nearly half (45%) reported having moderate AD, while 28% had severe AD. When asked about the overall disease burden of AD symptoms in the past month, 30% reported a significant impact on life, 28% reported a moderate impact score, 21% reported a high impact score, 18% reported a low impact score, and 3% of respondents reported no impact.

In the multivariable proportional odds analysis, moderate AD (odds ratio [OR], 4.13) and severe AD (OR, 13.63) were both associated with greater disease burden compared with mild AD. Also, spending 11 or more hours per week managing AD symptoms was associated with greater disease burden compared with 0 to 4 hours (an OR of 2.67 for 11-20 hours per week spent managing AD and OR of 5.34 for 21 or more hours per week spent managing AD).

Correlations between specific impact domains such as sleep, cognitive thinking, and physical activity and overall AD impact scores ranged from weak to moderate, and no individual aspect of disease burden correlated strongly with overall impact scores. The researchers observed similar results after they stratified the analysis by age, current severity, and time spent managing AD.

In other findings, 40% of study participants reported mild changes in mood related to their AD, 30% reported moderate changes, 9% reported severe changes, while the remainder reported no changes in mood. The variable most strongly associated with current mood changes was having severe AD at the time of the survey (OR 5.29).
 

Understanding of disease burden ‘limited’

“Atopic dermatitis is associated with an immense clinical burden,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “However, our understanding of disease burden from the patient perspective is limited,” he added.

“Interestingly, no single specific element of disease burden was strongly correlated with overall burden, further supporting the complex, multidimensional nature” of the impact of AD, he said, noting that the study “highlights the need for clinicians to look beyond the skin when it comes to AD and underscores the need for additional research to better understand the patient and caregiver perspective.”

Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, who was also asked to comment on the study, noted that aside from the well discussed impact and burden of itch and its impact on sleep loss, much remains to be learned about the full impact of AD, particularly among adults.

“For example, it is commonly accepted and expected that patients with more severe AD likely experience higher disease burden, but are there other factors that can influence this risk?” she asked. “Can we explain the high impact of AD disease aside from the level of disease severity, particularly among adults with AD?”

The study, she added, “is important because it provides additional insights into those possible factors, including ‘time spent managing their disease’ and ‘associated depression.’ In particular, understanding the association between ‘time spent managing their disease’ and higher disease burden is critical because, in my opinion, it emphasizes the need to develop better strategies for improving the care of patients with AD including the development of more efficacious and safer treatment strategies.”

Dr. Drucker and colleagues acknowledged certain limitations of the analysis, including its cross-sectional design, the potential for selection bias, and the fact that it did not use the patient-oriented outcome measure or the dermatology life quality index. “Further work to address the complex burden of AD, including strategies to reduce time spent managing AD, and understanding the fullness of the patient experience is needed,” they concluded.

The work was supported in part by a grant from the National Eczema Association (NEA). Dr. Drucker reported that he receives compensation from the British Journal of Dermatology (as reviewer and section editor), American Academy of Dermatology (guidelines writer), and NEA (grant reviewer). Coauthors representing the NEA and other patient organizations including the Allergy & Asthma Network, Asthma and Allergy Foundation of America, Global Parents for Eczema Research, and International Topical Steroid Awareness Network received organizational grants (Pfizer) and sponsorship funding for these analyses from AbbVie, Eli Lilly, Incyte, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi Genzyme.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, EPI Health, Incyte, L’Oréal, the NEA, Pfizer, Regeneron, Sanofi, and UCB.

Dr. Chiesa Fuxench disclosed that she has received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, and Vanda for work related to AD She has served as consultant for the Asthma and Allergy Foundation of America, NEA, AbbVie, Incyte Corporation, and Pfizer; and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer.

Among 1,065 adults with atopic dermatitis (AD) who were surveyed about their condition, no single element of disease burden, including sleep, stood out as having a strong association with overall disease burden. However, AD severity and spending 11 hours or more per week managing the condition did correlate with higher overall disease burden.

“Research has documented the disease burden of AD, including its visible nature and the effect on itch and sleep, but knowledge gaps remain,” Aaron M. Drucker, MD, of the division of dermatology at the University of Toronto, and colleagues wrote in the study published online in JAMA Dermatology. “Gaps include a poor understanding of symptoms other than itch, patients’ treatment experience, and how different elements of burden of disease interact.”

©aniaostudio/Thinkstock.com

Dr. Drucker and colleagues collected data from an externally led patient-focused drug development survey on AD, a 32-item questionnaire that was administered electronically between Aug. 1, 2019, and Oct. 11, 2019. Respondents were asked to rate the overall impact of their AD in the past months and the specific elements of disease burden on a 1-5 scale, with 1 meaning no impact, and 5 meaning a significant impact. They were also asked to rate current mood changes and mood changes at the worst point of AD on a 4-point scale that ranged from “not present” to “severe.” The researchers used multivariable ordinal regression to examine associations between demographic and clinical variables and patient-reported overall AD impact scores.
 

Survey results

Of the 1,065 respondents, 33% were aged 18-34 years, 50% were aged 35-50 years, 17% were aged 65 years or older, and 83% were female. Nearly half (45%) reported having moderate AD, while 28% had severe AD. When asked about the overall disease burden of AD symptoms in the past month, 30% reported a significant impact on life, 28% reported a moderate impact score, 21% reported a high impact score, 18% reported a low impact score, and 3% of respondents reported no impact.

In the multivariable proportional odds analysis, moderate AD (odds ratio [OR], 4.13) and severe AD (OR, 13.63) were both associated with greater disease burden compared with mild AD. Also, spending 11 or more hours per week managing AD symptoms was associated with greater disease burden compared with 0 to 4 hours (an OR of 2.67 for 11-20 hours per week spent managing AD and OR of 5.34 for 21 or more hours per week spent managing AD).

Correlations between specific impact domains such as sleep, cognitive thinking, and physical activity and overall AD impact scores ranged from weak to moderate, and no individual aspect of disease burden correlated strongly with overall impact scores. The researchers observed similar results after they stratified the analysis by age, current severity, and time spent managing AD.

In other findings, 40% of study participants reported mild changes in mood related to their AD, 30% reported moderate changes, 9% reported severe changes, while the remainder reported no changes in mood. The variable most strongly associated with current mood changes was having severe AD at the time of the survey (OR 5.29).
 

Understanding of disease burden ‘limited’

“Atopic dermatitis is associated with an immense clinical burden,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “However, our understanding of disease burden from the patient perspective is limited,” he added.

“Interestingly, no single specific element of disease burden was strongly correlated with overall burden, further supporting the complex, multidimensional nature” of the impact of AD, he said, noting that the study “highlights the need for clinicians to look beyond the skin when it comes to AD and underscores the need for additional research to better understand the patient and caregiver perspective.”

Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, who was also asked to comment on the study, noted that aside from the well discussed impact and burden of itch and its impact on sleep loss, much remains to be learned about the full impact of AD, particularly among adults.

“For example, it is commonly accepted and expected that patients with more severe AD likely experience higher disease burden, but are there other factors that can influence this risk?” she asked. “Can we explain the high impact of AD disease aside from the level of disease severity, particularly among adults with AD?”

The study, she added, “is important because it provides additional insights into those possible factors, including ‘time spent managing their disease’ and ‘associated depression.’ In particular, understanding the association between ‘time spent managing their disease’ and higher disease burden is critical because, in my opinion, it emphasizes the need to develop better strategies for improving the care of patients with AD including the development of more efficacious and safer treatment strategies.”

Dr. Drucker and colleagues acknowledged certain limitations of the analysis, including its cross-sectional design, the potential for selection bias, and the fact that it did not use the patient-oriented outcome measure or the dermatology life quality index. “Further work to address the complex burden of AD, including strategies to reduce time spent managing AD, and understanding the fullness of the patient experience is needed,” they concluded.

The work was supported in part by a grant from the National Eczema Association (NEA). Dr. Drucker reported that he receives compensation from the British Journal of Dermatology (as reviewer and section editor), American Academy of Dermatology (guidelines writer), and NEA (grant reviewer). Coauthors representing the NEA and other patient organizations including the Allergy & Asthma Network, Asthma and Allergy Foundation of America, Global Parents for Eczema Research, and International Topical Steroid Awareness Network received organizational grants (Pfizer) and sponsorship funding for these analyses from AbbVie, Eli Lilly, Incyte, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi Genzyme.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, EPI Health, Incyte, L’Oréal, the NEA, Pfizer, Regeneron, Sanofi, and UCB.

Dr. Chiesa Fuxench disclosed that she has received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, and Vanda for work related to AD She has served as consultant for the Asthma and Allergy Foundation of America, NEA, AbbVie, Incyte Corporation, and Pfizer; and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer.

Among 1,065 adults with atopic dermatitis (AD) who were surveyed about their condition, no single element of disease burden, including sleep, stood out as having a strong association with overall disease burden. However, AD severity and spending 11 hours or more per week managing the condition did correlate with higher overall disease burden.

“Research has documented the disease burden of AD, including its visible nature and the effect on itch and sleep, but knowledge gaps remain,” Aaron M. Drucker, MD, of the division of dermatology at the University of Toronto, and colleagues wrote in the study published online in JAMA Dermatology. “Gaps include a poor understanding of symptoms other than itch, patients’ treatment experience, and how different elements of burden of disease interact.”

©aniaostudio/Thinkstock.com

Dr. Drucker and colleagues collected data from an externally led patient-focused drug development survey on AD, a 32-item questionnaire that was administered electronically between Aug. 1, 2019, and Oct. 11, 2019. Respondents were asked to rate the overall impact of their AD in the past months and the specific elements of disease burden on a 1-5 scale, with 1 meaning no impact, and 5 meaning a significant impact. They were also asked to rate current mood changes and mood changes at the worst point of AD on a 4-point scale that ranged from “not present” to “severe.” The researchers used multivariable ordinal regression to examine associations between demographic and clinical variables and patient-reported overall AD impact scores.
 

Survey results

Of the 1,065 respondents, 33% were aged 18-34 years, 50% were aged 35-50 years, 17% were aged 65 years or older, and 83% were female. Nearly half (45%) reported having moderate AD, while 28% had severe AD. When asked about the overall disease burden of AD symptoms in the past month, 30% reported a significant impact on life, 28% reported a moderate impact score, 21% reported a high impact score, 18% reported a low impact score, and 3% of respondents reported no impact.

In the multivariable proportional odds analysis, moderate AD (odds ratio [OR], 4.13) and severe AD (OR, 13.63) were both associated with greater disease burden compared with mild AD. Also, spending 11 or more hours per week managing AD symptoms was associated with greater disease burden compared with 0 to 4 hours (an OR of 2.67 for 11-20 hours per week spent managing AD and OR of 5.34 for 21 or more hours per week spent managing AD).

Correlations between specific impact domains such as sleep, cognitive thinking, and physical activity and overall AD impact scores ranged from weak to moderate, and no individual aspect of disease burden correlated strongly with overall impact scores. The researchers observed similar results after they stratified the analysis by age, current severity, and time spent managing AD.

In other findings, 40% of study participants reported mild changes in mood related to their AD, 30% reported moderate changes, 9% reported severe changes, while the remainder reported no changes in mood. The variable most strongly associated with current mood changes was having severe AD at the time of the survey (OR 5.29).
 

Understanding of disease burden ‘limited’

“Atopic dermatitis is associated with an immense clinical burden,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “However, our understanding of disease burden from the patient perspective is limited,” he added.

“Interestingly, no single specific element of disease burden was strongly correlated with overall burden, further supporting the complex, multidimensional nature” of the impact of AD, he said, noting that the study “highlights the need for clinicians to look beyond the skin when it comes to AD and underscores the need for additional research to better understand the patient and caregiver perspective.”

Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, who was also asked to comment on the study, noted that aside from the well discussed impact and burden of itch and its impact on sleep loss, much remains to be learned about the full impact of AD, particularly among adults.

“For example, it is commonly accepted and expected that patients with more severe AD likely experience higher disease burden, but are there other factors that can influence this risk?” she asked. “Can we explain the high impact of AD disease aside from the level of disease severity, particularly among adults with AD?”

The study, she added, “is important because it provides additional insights into those possible factors, including ‘time spent managing their disease’ and ‘associated depression.’ In particular, understanding the association between ‘time spent managing their disease’ and higher disease burden is critical because, in my opinion, it emphasizes the need to develop better strategies for improving the care of patients with AD including the development of more efficacious and safer treatment strategies.”

Dr. Drucker and colleagues acknowledged certain limitations of the analysis, including its cross-sectional design, the potential for selection bias, and the fact that it did not use the patient-oriented outcome measure or the dermatology life quality index. “Further work to address the complex burden of AD, including strategies to reduce time spent managing AD, and understanding the fullness of the patient experience is needed,” they concluded.

The work was supported in part by a grant from the National Eczema Association (NEA). Dr. Drucker reported that he receives compensation from the British Journal of Dermatology (as reviewer and section editor), American Academy of Dermatology (guidelines writer), and NEA (grant reviewer). Coauthors representing the NEA and other patient organizations including the Allergy & Asthma Network, Asthma and Allergy Foundation of America, Global Parents for Eczema Research, and International Topical Steroid Awareness Network received organizational grants (Pfizer) and sponsorship funding for these analyses from AbbVie, Eli Lilly, Incyte, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi Genzyme.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, EPI Health, Incyte, L’Oréal, the NEA, Pfizer, Regeneron, Sanofi, and UCB.

Dr. Chiesa Fuxench disclosed that she has received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, and Vanda for work related to AD She has served as consultant for the Asthma and Allergy Foundation of America, NEA, AbbVie, Incyte Corporation, and Pfizer; and received honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi and Pfizer.

INDIANAPOLIS – Among children and adolescents diagnosed with melanoma, females had higher rates of superficial spreading disease, while males were more frequently affected by nodular melanoma.

In addition, male gender was independently associated with increased mortality, but age was not.

Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.

“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”

Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.

Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).

Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).

Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).

In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).

When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.

“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”

She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”

Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.

Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”

Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Among children and adolescents diagnosed with melanoma, females had higher rates of superficial spreading disease, while males were more frequently affected by nodular melanoma.

In addition, male gender was independently associated with increased mortality, but age was not.

Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.

“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”

Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.

Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).

Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).

Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).

In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).

When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.

“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”

She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”

Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.

Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”

Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Among children and adolescents diagnosed with melanoma, females had higher rates of superficial spreading disease, while males were more frequently affected by nodular melanoma.

In addition, male gender was independently associated with increased mortality, but age was not.

Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.

“There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males,” co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona, Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session. “However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma.”

Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona, Phoenix, Dr. Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018. The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.

Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Dr. Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and “unspecified” (1.9% vs. 3.7%).

Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).

Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).

In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).

When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.

“It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males,” Dr. Thiede said. “When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential,” she advised. “It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis.”

She acknowledged certain limitations of the study, including its reliance on one database, “as comparing multiple databases would strengthen the conclusions,” she said. “There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival.”

Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children’s Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females “could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma.” Those differences “could influence how providers evaluate melanocytic lesions in children,” she added.

Dr. Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children’s Hospital, said it was “interesting” that the authors found no association between older age and an increased risk of death. “It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas,” she said. “Also, knowing the distribution of melanoma across the age categories could provide more insight into their data.”

Ms. Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

We have attended grand rounds presentations at which students announce that Mohs micrographic surgery evaluates 100% of the surgical margin, whereas standard excision samples 1% to 2% of the margin; we have even fielded questions from neighbors who have come across this information on the internet.^1-5 This statement describes a best-case scenario for Mohs surgery and a worst-case scenario for standard excision. We believe that it is important for clinicians to have a more nuanced understanding of how simple excisions are processed so that they can have pertinent discussions with patients, especially now that there is increasing access to personal health information along with increased agency in patient decision-making.

Margins for Mohs Surgery

Theoretically, Mohs surgery should sample all true surgical margins by complete circumferential, peripheral, and deep-margin assessment. Unfortunately, some sections are not cut full face—sections may not always sample a complete surface—when technicians make an error or lack expertise. Some sections may have small tissue folds or small gaps that prevent complete visualization. We estimate that the Mohs sections we review in consultation that are prepared by private practice Mohs surgeons in our communities visualize approximately 98% of surgical margins on average. Incomplete sections contribute to the rare tumor recurrences after Mohs surgery of approximately 2% to 3%.⁶

Standard Excision Margins

When we obtained the references cited in articles asserting that standard excision samples less than 0.5%, 1%, or 2% of the surgical margin, we did not find evidence-based information confirming this generally accepted conclusion. We believe the assertions are derived by comparing the sum of the thickness of all microscopic sections added together against the longitudinal length of the entire specimen.Sampling less than 0.5% of a margin has been described as providing the illusion of microscopic control.⁵ We have encountered medical students, nondermatologist physicians, and patients who have come across this information and have understandably concluded that standard margin assessment must be inadequate if only such a small amount of margin is assessed.

Here is a simple example to show that more margin is accessed in some cases. Consider this hypothetical situation: If a tumor can be readily visualized grossly and housed entirely within an imaginary cuboid (rectangular) prism that is removed in an elliptical specimen with a length of 6 cm, a width of 2 cm, and a height of 1 cm (Figure), then standard sectioning assesses a greater margin.

Bread-loaf sectioning would be expected to examine the complete surface of 2 sides (faces) of the cuboid. Assessing 2 of the 5 clinically relevant sides provides information for approximately 50% of the margins, as sections in the next parallel plane can be expected to be clear after the first clear section is identified. The clinically useful information is not limited to the sum of the widths of sections. Encountering a clear plane typically indicates that there will be no tumor in more distal parallel planes. Warne et al⁶ developed a formula that can accurately predict the percentage of the margin evaluated by proxy that considers the curvature of the ellipse.

Comparing Standard Excision and Mohs Surgery

Mohs surgery consistently results in the best outcomes, but standard excision is effective, too. Standard excision is relatively simple, requires less equipment, is less time consuming, and can provide good value when resources are finite. Data on recurrence of basal cell carcinoma after simple excision are limited, but the recurrence rate is reported to be approximately 3%.^7,8 A meta-analysis found that the recurrence rate of basal cell carcinoma treated with standard excision was 0.4%, 1.6%, 2.6%, and 4% with 5-mm, 4-mm, 3-mm, and 2-mm surgical margins, respectively.⁹

Mohs surgery is the best, most effective, and most tissue-sparing technique for certain nonmelanoma skin cancers. This observation is reflected in guidelines worldwide.¹⁰ The adequacy of standard approaches to margin evaluation depends on the capabilities and focus of the laboratory team. Dermatopathologists often are called to the laboratory to decide which technique will be best for a particular case.¹¹ Technicians are trained to take more sections in areas where abnormalities are seen, and some laboratories take photographs of specimens or provide sketches for correlation. Dermatopathologists also routinely request additional sections in areas where visible tumor extends close to surgical margins on microscopic examination.

It is not simply a matter of knowing how much of the margin is sampled but if the most pertinent areas are adequately sampled. Simple sectioning can work well and be cost effective. Many clinicians are unaware of how tissue processing can vary from laboratory to laboratory. There are no uniformly accepted standards for how tissue should be processed. Assiduous and thoughtful evaluation of specimens can affect results. As with any service, some laboratories provide more detailed and conscientious care while others focus more on immediate costs. Clinicians should understand how their specimens are processed by discussing margin evaluation with their dermatopathologist.

Final Thoughts

Used appropriately, Mohs surgery is an excellent technique that can provide outstanding results. Standard excision also has an important place in the dermatologist’s armamentarium and typically provides information about more than 1% to 2% of the margin. Understanding the techniques used to process specimens is critical to delivering the best possible care.

We have attended grand rounds presentations at which students announce that Mohs micrographic surgery evaluates 100% of the surgical margin, whereas standard excision samples 1% to 2% of the margin; we have even fielded questions from neighbors who have come across this information on the internet.^1-5 This statement describes a best-case scenario for Mohs surgery and a worst-case scenario for standard excision. We believe that it is important for clinicians to have a more nuanced understanding of how simple excisions are processed so that they can have pertinent discussions with patients, especially now that there is increasing access to personal health information along with increased agency in patient decision-making.

Margins for Mohs Surgery

Theoretically, Mohs surgery should sample all true surgical margins by complete circumferential, peripheral, and deep-margin assessment. Unfortunately, some sections are not cut full face—sections may not always sample a complete surface—when technicians make an error or lack expertise. Some sections may have small tissue folds or small gaps that prevent complete visualization. We estimate that the Mohs sections we review in consultation that are prepared by private practice Mohs surgeons in our communities visualize approximately 98% of surgical margins on average. Incomplete sections contribute to the rare tumor recurrences after Mohs surgery of approximately 2% to 3%.⁶

Standard Excision Margins

When we obtained the references cited in articles asserting that standard excision samples less than 0.5%, 1%, or 2% of the surgical margin, we did not find evidence-based information confirming this generally accepted conclusion. We believe the assertions are derived by comparing the sum of the thickness of all microscopic sections added together against the longitudinal length of the entire specimen.Sampling less than 0.5% of a margin has been described as providing the illusion of microscopic control.⁵ We have encountered medical students, nondermatologist physicians, and patients who have come across this information and have understandably concluded that standard margin assessment must be inadequate if only such a small amount of margin is assessed.

Here is a simple example to show that more margin is accessed in some cases. Consider this hypothetical situation: If a tumor can be readily visualized grossly and housed entirely within an imaginary cuboid (rectangular) prism that is removed in an elliptical specimen with a length of 6 cm, a width of 2 cm, and a height of 1 cm (Figure), then standard sectioning assesses a greater margin.

Bread-loaf sectioning would be expected to examine the complete surface of 2 sides (faces) of the cuboid. Assessing 2 of the 5 clinically relevant sides provides information for approximately 50% of the margins, as sections in the next parallel plane can be expected to be clear after the first clear section is identified. The clinically useful information is not limited to the sum of the widths of sections. Encountering a clear plane typically indicates that there will be no tumor in more distal parallel planes. Warne et al⁶ developed a formula that can accurately predict the percentage of the margin evaluated by proxy that considers the curvature of the ellipse.

Comparing Standard Excision and Mohs Surgery

Mohs surgery consistently results in the best outcomes, but standard excision is effective, too. Standard excision is relatively simple, requires less equipment, is less time consuming, and can provide good value when resources are finite. Data on recurrence of basal cell carcinoma after simple excision are limited, but the recurrence rate is reported to be approximately 3%.^7,8 A meta-analysis found that the recurrence rate of basal cell carcinoma treated with standard excision was 0.4%, 1.6%, 2.6%, and 4% with 5-mm, 4-mm, 3-mm, and 2-mm surgical margins, respectively.⁹

Mohs surgery is the best, most effective, and most tissue-sparing technique for certain nonmelanoma skin cancers. This observation is reflected in guidelines worldwide.¹⁰ The adequacy of standard approaches to margin evaluation depends on the capabilities and focus of the laboratory team. Dermatopathologists often are called to the laboratory to decide which technique will be best for a particular case.¹¹ Technicians are trained to take more sections in areas where abnormalities are seen, and some laboratories take photographs of specimens or provide sketches for correlation. Dermatopathologists also routinely request additional sections in areas where visible tumor extends close to surgical margins on microscopic examination.

It is not simply a matter of knowing how much of the margin is sampled but if the most pertinent areas are adequately sampled. Simple sectioning can work well and be cost effective. Many clinicians are unaware of how tissue processing can vary from laboratory to laboratory. There are no uniformly accepted standards for how tissue should be processed. Assiduous and thoughtful evaluation of specimens can affect results. As with any service, some laboratories provide more detailed and conscientious care while others focus more on immediate costs. Clinicians should understand how their specimens are processed by discussing margin evaluation with their dermatopathologist.

Final Thoughts

Used appropriately, Mohs surgery is an excellent technique that can provide outstanding results. Standard excision also has an important place in the dermatologist’s armamentarium and typically provides information about more than 1% to 2% of the margin. Understanding the techniques used to process specimens is critical to delivering the best possible care.

We have attended grand rounds presentations at which students announce that Mohs micrographic surgery evaluates 100% of the surgical margin, whereas standard excision samples 1% to 2% of the margin; we have even fielded questions from neighbors who have come across this information on the internet.^1-5 This statement describes a best-case scenario for Mohs surgery and a worst-case scenario for standard excision. We believe that it is important for clinicians to have a more nuanced understanding of how simple excisions are processed so that they can have pertinent discussions with patients, especially now that there is increasing access to personal health information along with increased agency in patient decision-making.

Margins for Mohs Surgery

Theoretically, Mohs surgery should sample all true surgical margins by complete circumferential, peripheral, and deep-margin assessment. Unfortunately, some sections are not cut full face—sections may not always sample a complete surface—when technicians make an error or lack expertise. Some sections may have small tissue folds or small gaps that prevent complete visualization. We estimate that the Mohs sections we review in consultation that are prepared by private practice Mohs surgeons in our communities visualize approximately 98% of surgical margins on average. Incomplete sections contribute to the rare tumor recurrences after Mohs surgery of approximately 2% to 3%.⁶

Standard Excision Margins

When we obtained the references cited in articles asserting that standard excision samples less than 0.5%, 1%, or 2% of the surgical margin, we did not find evidence-based information confirming this generally accepted conclusion. We believe the assertions are derived by comparing the sum of the thickness of all microscopic sections added together against the longitudinal length of the entire specimen.Sampling less than 0.5% of a margin has been described as providing the illusion of microscopic control.⁵ We have encountered medical students, nondermatologist physicians, and patients who have come across this information and have understandably concluded that standard margin assessment must be inadequate if only such a small amount of margin is assessed.

Here is a simple example to show that more margin is accessed in some cases. Consider this hypothetical situation: If a tumor can be readily visualized grossly and housed entirely within an imaginary cuboid (rectangular) prism that is removed in an elliptical specimen with a length of 6 cm, a width of 2 cm, and a height of 1 cm (Figure), then standard sectioning assesses a greater margin.

Bread-loaf sectioning would be expected to examine the complete surface of 2 sides (faces) of the cuboid. Assessing 2 of the 5 clinically relevant sides provides information for approximately 50% of the margins, as sections in the next parallel plane can be expected to be clear after the first clear section is identified. The clinically useful information is not limited to the sum of the widths of sections. Encountering a clear plane typically indicates that there will be no tumor in more distal parallel planes. Warne et al⁶ developed a formula that can accurately predict the percentage of the margin evaluated by proxy that considers the curvature of the ellipse.

Comparing Standard Excision and Mohs Surgery

Mohs surgery consistently results in the best outcomes, but standard excision is effective, too. Standard excision is relatively simple, requires less equipment, is less time consuming, and can provide good value when resources are finite. Data on recurrence of basal cell carcinoma after simple excision are limited, but the recurrence rate is reported to be approximately 3%.^7,8 A meta-analysis found that the recurrence rate of basal cell carcinoma treated with standard excision was 0.4%, 1.6%, 2.6%, and 4% with 5-mm, 4-mm, 3-mm, and 2-mm surgical margins, respectively.⁹

Mohs surgery is the best, most effective, and most tissue-sparing technique for certain nonmelanoma skin cancers. This observation is reflected in guidelines worldwide.¹⁰ The adequacy of standard approaches to margin evaluation depends on the capabilities and focus of the laboratory team. Dermatopathologists often are called to the laboratory to decide which technique will be best for a particular case.¹¹ Technicians are trained to take more sections in areas where abnormalities are seen, and some laboratories take photographs of specimens or provide sketches for correlation. Dermatopathologists also routinely request additional sections in areas where visible tumor extends close to surgical margins on microscopic examination.

It is not simply a matter of knowing how much of the margin is sampled but if the most pertinent areas are adequately sampled. Simple sectioning can work well and be cost effective. Many clinicians are unaware of how tissue processing can vary from laboratory to laboratory. There are no uniformly accepted standards for how tissue should be processed. Assiduous and thoughtful evaluation of specimens can affect results. As with any service, some laboratories provide more detailed and conscientious care while others focus more on immediate costs. Clinicians should understand how their specimens are processed by discussing margin evaluation with their dermatopathologist.

Final Thoughts

Used appropriately, Mohs surgery is an excellent technique that can provide outstanding results. Standard excision also has an important place in the dermatologist’s armamentarium and typically provides information about more than 1% to 2% of the margin. Understanding the techniques used to process specimens is critical to delivering the best possible care.

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

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

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

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

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

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