Cutis

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

Practice Gap

A male patient presented with 2 concerning lesions, which histopathology revealed were invasive squamous cell carcinoma (SCC) on the right medial chest and SCC in situ on the right upper scapular region. Both were treated with wide local excision; margins were clear in our office the same day.

This case highlighted a practice gap in postoperative care. Two factors posed a challenge to proper postoperative wound care for our patient:

• Because of the high risk of transmission of SARS-CoV-2, the patient hoped to limit exposure by avoiding an office visit to remove the bandage.

• The patient did not have someone at home to serve as an immediate support system, which made it impossible for him to rely on others for postoperative wound care.

Previously, the patient had to ask a friend to remove a bandage for melanoma in situ on the inner aspect of the left upper arm. Therefore, after this procedure, the patient asked if the bandage could be fashioned in a manner that would allow him to remove it without assistance (Figure 1).

Technique

In constructing a bandage that is easier to remove, some necessary pressure that is provided by the bandage often is sacrificed by making it looser. Considering that our patient had moderate bleeding during the procedure—in part because he took low-dose aspirin (81 mg/d)—it was important to maintain firm pressure under the bandage postoperatively to help prevent untoward bleeding. Furthermore, because of the location of the treated site and the patient’s limited range of motion, it was not feasible for him to reach the area on the scapula and remove the bandage.¹

For easy self-removal, we designed a bandage with a pull tab that was within the patient’s reach. Suitable materials for the pull tab bandage included surgical tape, bandaging tape with adequate stretch, sterile nonadhesive gauze, fenestrated surgical gauze, and a topical emollient such as petroleum jelly or antibacterial ointment.

To clean the site and decrease the amount of oil that would reduce the effectiveness of the adhesive, the wound was prepared with 70% alcohol. The site was then treated with petroleum jelly.

Next, we designed 2 pull tab bandage prototypes that allowed easy self-removal. For both prototypes, sterile nonadhesive gauze was applied to the wound along with folded and fenestrated gauze, which provided pressure. We used prototype #1 in our patient, and prototype #2 was demonstrated as an option.

Prototype #1—We created 2 tabs—each 2-feet long—using bandaging tape that was folded on itself once horizontally (Figure 2). The tabs were aligned on either side of the wound, the tops of which sat approximately 2 inches above the top of the first layer of adhesive bandage. An initial layer of adhesive surgical dressing was applied to cover the wound; 1 inch of the dressing was left exposed on the top of each tab. In addition, there were 2 “feet” running on the bottom.

The tops of the tabs were folded back over the adhesive tape, creating a type of “hook.” An additional final layer of adhesive tape was applied to ensure adequate pressure on the surgical site.

The patient was instructed to remove the bandage 2 days after the procedure. The outcome was qualified through a 3-day postoperative telephone call. The patient was asked about postoperative pain and his level of satisfaction with treatment. He was asked if he had any changes such as bleeding, swelling, signs of infection, or increased pain in the days after surgery or perceived postoperative complications, such as irritation. We asked the patient about the relative ease of removing the bandage and if removal was painful. He reported that the bandage was easy to remove, and that doing so was not painful; furthermore, he did not have problems with the bandage or healing and did not experience any medical changes. He found the bandage to be comfortable. The patient stated that the hanging feet of the prototype #1 bandage were not bothersome and were sturdy for the time that the bandage was on.

Prototype #2—We prepared a bandage using surgical packing as the tab (Figure 3). The packing was slowly placed around the site, which was already covered with nonadhesive gauze and fenestrated surgical gauze, with adequate spacing between each loop (for a total of 3 loops), 1 of which crossed over the third loop so that the adhesive bandaging tape could be removed easily. This allowed for a single tab that could be removed by a single pull. A final layer of adhesive tape was applied to ensure adequate pressure, similar to prototype #1. The same postoperative protocol was employed to provide a consistent standard of care. We recommend use of this prototype when surgical tape is not available, and surgical packing can be used as a substitute.

Practice Implications

Patients have a better appreciation for avoiding excess visits to medical offices due to the COVID-19 pandemic. The risk for exposure to SARS-CoV-2 infection is greater when patients who lack a support system must return to the office for aftercare or to have a bandage removed. Although protection offered by the COVID-19 vaccine alleviates concern, many patients have realized the benefits of only visiting medical offices in person when necessary.

The concept of pull tab bandages that can be removed by the patient at home has other applications. For example, patients who travel a long distance to see their physician will benefit from easier aftercare and avoid additional follow-up visits when provided with a self-removable bandage.

Practice Gap

A male patient presented with 2 concerning lesions, which histopathology revealed were invasive squamous cell carcinoma (SCC) on the right medial chest and SCC in situ on the right upper scapular region. Both were treated with wide local excision; margins were clear in our office the same day.

This case highlighted a practice gap in postoperative care. Two factors posed a challenge to proper postoperative wound care for our patient:

• Because of the high risk of transmission of SARS-CoV-2, the patient hoped to limit exposure by avoiding an office visit to remove the bandage.

• The patient did not have someone at home to serve as an immediate support system, which made it impossible for him to rely on others for postoperative wound care.

Previously, the patient had to ask a friend to remove a bandage for melanoma in situ on the inner aspect of the left upper arm. Therefore, after this procedure, the patient asked if the bandage could be fashioned in a manner that would allow him to remove it without assistance (Figure 1).

Technique

In constructing a bandage that is easier to remove, some necessary pressure that is provided by the bandage often is sacrificed by making it looser. Considering that our patient had moderate bleeding during the procedure—in part because he took low-dose aspirin (81 mg/d)—it was important to maintain firm pressure under the bandage postoperatively to help prevent untoward bleeding. Furthermore, because of the location of the treated site and the patient’s limited range of motion, it was not feasible for him to reach the area on the scapula and remove the bandage.¹

For easy self-removal, we designed a bandage with a pull tab that was within the patient’s reach. Suitable materials for the pull tab bandage included surgical tape, bandaging tape with adequate stretch, sterile nonadhesive gauze, fenestrated surgical gauze, and a topical emollient such as petroleum jelly or antibacterial ointment.

To clean the site and decrease the amount of oil that would reduce the effectiveness of the adhesive, the wound was prepared with 70% alcohol. The site was then treated with petroleum jelly.

Next, we designed 2 pull tab bandage prototypes that allowed easy self-removal. For both prototypes, sterile nonadhesive gauze was applied to the wound along with folded and fenestrated gauze, which provided pressure. We used prototype #1 in our patient, and prototype #2 was demonstrated as an option.

Prototype #1—We created 2 tabs—each 2-feet long—using bandaging tape that was folded on itself once horizontally (Figure 2). The tabs were aligned on either side of the wound, the tops of which sat approximately 2 inches above the top of the first layer of adhesive bandage. An initial layer of adhesive surgical dressing was applied to cover the wound; 1 inch of the dressing was left exposed on the top of each tab. In addition, there were 2 “feet” running on the bottom.

The tops of the tabs were folded back over the adhesive tape, creating a type of “hook.” An additional final layer of adhesive tape was applied to ensure adequate pressure on the surgical site.

The patient was instructed to remove the bandage 2 days after the procedure. The outcome was qualified through a 3-day postoperative telephone call. The patient was asked about postoperative pain and his level of satisfaction with treatment. He was asked if he had any changes such as bleeding, swelling, signs of infection, or increased pain in the days after surgery or perceived postoperative complications, such as irritation. We asked the patient about the relative ease of removing the bandage and if removal was painful. He reported that the bandage was easy to remove, and that doing so was not painful; furthermore, he did not have problems with the bandage or healing and did not experience any medical changes. He found the bandage to be comfortable. The patient stated that the hanging feet of the prototype #1 bandage were not bothersome and were sturdy for the time that the bandage was on.

Prototype #2—We prepared a bandage using surgical packing as the tab (Figure 3). The packing was slowly placed around the site, which was already covered with nonadhesive gauze and fenestrated surgical gauze, with adequate spacing between each loop (for a total of 3 loops), 1 of which crossed over the third loop so that the adhesive bandaging tape could be removed easily. This allowed for a single tab that could be removed by a single pull. A final layer of adhesive tape was applied to ensure adequate pressure, similar to prototype #1. The same postoperative protocol was employed to provide a consistent standard of care. We recommend use of this prototype when surgical tape is not available, and surgical packing can be used as a substitute.

Practice Implications

Patients have a better appreciation for avoiding excess visits to medical offices due to the COVID-19 pandemic. The risk for exposure to SARS-CoV-2 infection is greater when patients who lack a support system must return to the office for aftercare or to have a bandage removed. Although protection offered by the COVID-19 vaccine alleviates concern, many patients have realized the benefits of only visiting medical offices in person when necessary.

The concept of pull tab bandages that can be removed by the patient at home has other applications. For example, patients who travel a long distance to see their physician will benefit from easier aftercare and avoid additional follow-up visits when provided with a self-removable bandage.

Practice Gap

A male patient presented with 2 concerning lesions, which histopathology revealed were invasive squamous cell carcinoma (SCC) on the right medial chest and SCC in situ on the right upper scapular region. Both were treated with wide local excision; margins were clear in our office the same day.

This case highlighted a practice gap in postoperative care. Two factors posed a challenge to proper postoperative wound care for our patient:

• Because of the high risk of transmission of SARS-CoV-2, the patient hoped to limit exposure by avoiding an office visit to remove the bandage.

• The patient did not have someone at home to serve as an immediate support system, which made it impossible for him to rely on others for postoperative wound care.

Previously, the patient had to ask a friend to remove a bandage for melanoma in situ on the inner aspect of the left upper arm. Therefore, after this procedure, the patient asked if the bandage could be fashioned in a manner that would allow him to remove it without assistance (Figure 1).

Technique

In constructing a bandage that is easier to remove, some necessary pressure that is provided by the bandage often is sacrificed by making it looser. Considering that our patient had moderate bleeding during the procedure—in part because he took low-dose aspirin (81 mg/d)—it was important to maintain firm pressure under the bandage postoperatively to help prevent untoward bleeding. Furthermore, because of the location of the treated site and the patient’s limited range of motion, it was not feasible for him to reach the area on the scapula and remove the bandage.¹

For easy self-removal, we designed a bandage with a pull tab that was within the patient’s reach. Suitable materials for the pull tab bandage included surgical tape, bandaging tape with adequate stretch, sterile nonadhesive gauze, fenestrated surgical gauze, and a topical emollient such as petroleum jelly or antibacterial ointment.

To clean the site and decrease the amount of oil that would reduce the effectiveness of the adhesive, the wound was prepared with 70% alcohol. The site was then treated with petroleum jelly.

Next, we designed 2 pull tab bandage prototypes that allowed easy self-removal. For both prototypes, sterile nonadhesive gauze was applied to the wound along with folded and fenestrated gauze, which provided pressure. We used prototype #1 in our patient, and prototype #2 was demonstrated as an option.

Prototype #1—We created 2 tabs—each 2-feet long—using bandaging tape that was folded on itself once horizontally (Figure 2). The tabs were aligned on either side of the wound, the tops of which sat approximately 2 inches above the top of the first layer of adhesive bandage. An initial layer of adhesive surgical dressing was applied to cover the wound; 1 inch of the dressing was left exposed on the top of each tab. In addition, there were 2 “feet” running on the bottom.

The tops of the tabs were folded back over the adhesive tape, creating a type of “hook.” An additional final layer of adhesive tape was applied to ensure adequate pressure on the surgical site.

The patient was instructed to remove the bandage 2 days after the procedure. The outcome was qualified through a 3-day postoperative telephone call. The patient was asked about postoperative pain and his level of satisfaction with treatment. He was asked if he had any changes such as bleeding, swelling, signs of infection, or increased pain in the days after surgery or perceived postoperative complications, such as irritation. We asked the patient about the relative ease of removing the bandage and if removal was painful. He reported that the bandage was easy to remove, and that doing so was not painful; furthermore, he did not have problems with the bandage or healing and did not experience any medical changes. He found the bandage to be comfortable. The patient stated that the hanging feet of the prototype #1 bandage were not bothersome and were sturdy for the time that the bandage was on.

Prototype #2—We prepared a bandage using surgical packing as the tab (Figure 3). The packing was slowly placed around the site, which was already covered with nonadhesive gauze and fenestrated surgical gauze, with adequate spacing between each loop (for a total of 3 loops), 1 of which crossed over the third loop so that the adhesive bandaging tape could be removed easily. This allowed for a single tab that could be removed by a single pull. A final layer of adhesive tape was applied to ensure adequate pressure, similar to prototype #1. The same postoperative protocol was employed to provide a consistent standard of care. We recommend use of this prototype when surgical tape is not available, and surgical packing can be used as a substitute.

Practice Implications

Patients have a better appreciation for avoiding excess visits to medical offices due to the COVID-19 pandemic. The risk for exposure to SARS-CoV-2 infection is greater when patients who lack a support system must return to the office for aftercare or to have a bandage removed. Although protection offered by the COVID-19 vaccine alleviates concern, many patients have realized the benefits of only visiting medical offices in person when necessary.

The concept of pull tab bandages that can be removed by the patient at home has other applications. For example, patients who travel a long distance to see their physician will benefit from easier aftercare and avoid additional follow-up visits when provided with a self-removable bandage.

The Diagnosis: IgA Pemphigus

Histopathology revealed a neutrophilic pustule and vesicle formation underlying the corneal layer (Figure). Direct immunofluorescence (DIF) showed weak positive staining for IgA within the intercellular keratinocyte in the epithelial compartment and a negative pattern with IgG, IgM, C3, and fibrinogen. The patient received a 40-mg intralesional triamcinolone injection and was placed on an oral prednisone 50-mg taper within 5 days. The plaques, bullae, and pustules began to resolve, but the lesions returned 1 day later. Oral prednisone 10 mg daily was initiated for 1 month, which resulted in full resolution of the lesions.

IgA pemphigus is a rare autoimmune disorder characterized by the occurrence of painful pruritic blisters caused by circulating IgA antibodies, which react against keratinocyte cellular components responsible for mediating cell-to-cell adherence.¹ The etiology of IgA pemphigus presently remains elusive, though it has been reported to occur concomitantly with several chronic malignancies and inflammatory conditions. Although its etiology is unknown, IgA pemphigus most commonly is treated with oral dapsone and corticosteroids.²

IgA pemphigus can be divided into 2 primary subtypes: subcorneal pustular dermatosis and intraepidermal neutrophilic dermatosis.^1,3 The former is characterized by intercellular deposition of IgA that reacts to the glycoprotein desmocollin-1 in the upper layer of the epidermis. Intraepidermal neutrophilic dermatosis is distinguished by the presence of autoantibodies against the desmoglein members of the cadherin superfamily of proteins. Additionally, unlike subcorneal pustular dermatosis, intraepidermal neutrophilic dermatosis autoantibody reactivity occurs in the lower epidermis.⁴

The differential includes dermatitis herpetiformis, which is commonly seen on the elbows, knees, and buttocks, with DIF showing IgA deposition at the dermal papillae. Pemphigus foliaceus is distributed on the scalp, face, and trunk, with DIF showing IgG intercellular deposition. Pustular psoriasis presents as erythematous sterile pustules in a more localized annular pattern. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) has similar clinical and histological findings to IgA pemphigus; however, DIF is negative.

The Diagnosis: IgA Pemphigus

Histopathology revealed a neutrophilic pustule and vesicle formation underlying the corneal layer (Figure). Direct immunofluorescence (DIF) showed weak positive staining for IgA within the intercellular keratinocyte in the epithelial compartment and a negative pattern with IgG, IgM, C3, and fibrinogen. The patient received a 40-mg intralesional triamcinolone injection and was placed on an oral prednisone 50-mg taper within 5 days. The plaques, bullae, and pustules began to resolve, but the lesions returned 1 day later. Oral prednisone 10 mg daily was initiated for 1 month, which resulted in full resolution of the lesions.

IgA pemphigus is a rare autoimmune disorder characterized by the occurrence of painful pruritic blisters caused by circulating IgA antibodies, which react against keratinocyte cellular components responsible for mediating cell-to-cell adherence.¹ The etiology of IgA pemphigus presently remains elusive, though it has been reported to occur concomitantly with several chronic malignancies and inflammatory conditions. Although its etiology is unknown, IgA pemphigus most commonly is treated with oral dapsone and corticosteroids.²

IgA pemphigus can be divided into 2 primary subtypes: subcorneal pustular dermatosis and intraepidermal neutrophilic dermatosis.^1,3 The former is characterized by intercellular deposition of IgA that reacts to the glycoprotein desmocollin-1 in the upper layer of the epidermis. Intraepidermal neutrophilic dermatosis is distinguished by the presence of autoantibodies against the desmoglein members of the cadherin superfamily of proteins. Additionally, unlike subcorneal pustular dermatosis, intraepidermal neutrophilic dermatosis autoantibody reactivity occurs in the lower epidermis.⁴

The differential includes dermatitis herpetiformis, which is commonly seen on the elbows, knees, and buttocks, with DIF showing IgA deposition at the dermal papillae. Pemphigus foliaceus is distributed on the scalp, face, and trunk, with DIF showing IgG intercellular deposition. Pustular psoriasis presents as erythematous sterile pustules in a more localized annular pattern. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) has similar clinical and histological findings to IgA pemphigus; however, DIF is negative.

The Diagnosis: IgA Pemphigus

Histopathology revealed a neutrophilic pustule and vesicle formation underlying the corneal layer (Figure). Direct immunofluorescence (DIF) showed weak positive staining for IgA within the intercellular keratinocyte in the epithelial compartment and a negative pattern with IgG, IgM, C3, and fibrinogen. The patient received a 40-mg intralesional triamcinolone injection and was placed on an oral prednisone 50-mg taper within 5 days. The plaques, bullae, and pustules began to resolve, but the lesions returned 1 day later. Oral prednisone 10 mg daily was initiated for 1 month, which resulted in full resolution of the lesions.

IgA pemphigus is a rare autoimmune disorder characterized by the occurrence of painful pruritic blisters caused by circulating IgA antibodies, which react against keratinocyte cellular components responsible for mediating cell-to-cell adherence.¹ The etiology of IgA pemphigus presently remains elusive, though it has been reported to occur concomitantly with several chronic malignancies and inflammatory conditions. Although its etiology is unknown, IgA pemphigus most commonly is treated with oral dapsone and corticosteroids.²

IgA pemphigus can be divided into 2 primary subtypes: subcorneal pustular dermatosis and intraepidermal neutrophilic dermatosis.^1,3 The former is characterized by intercellular deposition of IgA that reacts to the glycoprotein desmocollin-1 in the upper layer of the epidermis. Intraepidermal neutrophilic dermatosis is distinguished by the presence of autoantibodies against the desmoglein members of the cadherin superfamily of proteins. Additionally, unlike subcorneal pustular dermatosis, intraepidermal neutrophilic dermatosis autoantibody reactivity occurs in the lower epidermis.⁴

The differential includes dermatitis herpetiformis, which is commonly seen on the elbows, knees, and buttocks, with DIF showing IgA deposition at the dermal papillae. Pemphigus foliaceus is distributed on the scalp, face, and trunk, with DIF showing IgG intercellular deposition. Pustular psoriasis presents as erythematous sterile pustules in a more localized annular pattern. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) has similar clinical and histological findings to IgA pemphigus; however, DIF is negative.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Perineuriomas are benign, slow-growing tumors derived from perineurial cells,¹ which form the structurally supportive perineurium that surrounds individual nerve fascicles.^2,3 Perineuriomas are classified into 2 main forms: intraneural or extraneural.⁴ Intraneural perineuriomas are found within the border of the peripheral nerve,⁵ while extraneural perineuriomas usually are found in soft tissue and skin. Extraneural perineuriomas can be further classified into variants based on their histologic appearance, including reticular, sclerosing, and plexiform subtypes. Extraneural perineuriomas usually present on the extremities or trunk of young to middle-aged adults as a well-circumscribed, painless, subcutaneous masses.¹ These tumors are especially unusual in children.⁴ We present 2 extraneural perineurioma cases in children, and we review the pertinent diagnostic features of perineurioma as well as the presentation in the pediatric population.

Case Reports

Patient 1—A 10-year-old boy with a history of cerebral palsy and related comorbidities presented to the clinic for evaluation of a lesion on the thigh with no associated pain, irritation, erythema, or drainage. Physical examination revealed a soft, pedunculated, mobile nodule on the right medial thigh. An elliptical excision was performed. Gross examination demonstrated a 2.0×2.0×1.8-cm polypoid nodule. Histologic examination showed a dermal-based proliferation of bland spindle cells (Figure 1). The cytomorphology was characterized by elongated tapering nuclei and many areas with delicate bipolar cytoplasmic processes. The constituent cells were arranged in a whorled pattern in a variably myxoid to collagenous stroma. The tumor cells were multifocally positive for CD34; focally positive for smooth muscle actin (SMA); and negative for S-100, epithelial membrane antigen (EMA), GLUT1, claudin-1, STAT6, and desmin. Rb protein was intact. The CD34 immunostain highlighted the cytoplasmic processes. Electron microscopy was performed because the immunohistochemical results were nonspecific despite the favorable histologic features for perineurioma and showed pinocytic vesicles with delicate cytoplasmic processes, characteristic of perineurioma (Figure 2). Follow-up visits were related to the management of multiple comorbidities; no known recurrence of the lesion was documented.

Patient 2—A 15-year-old adolescent boy with no notable medical history presented to the pediatric clinic for a bump on the right upper arm of 4 to 5 months’ duration. He did not recall an injury to the area and denied change in size, redness, bruising, or pain of the lesion. Ultrasonography demonstrated a 2.6×2.3×1.3-cm hypoechoic and slightly heterogeneous, well-circumscribed, subcutaneous mass with internal vascularity. The patient was then referred to a pediatric surgeon. The clinical differential included a lipoma, lymphadenopathy, or sebaceous cyst. An excision was performed. Gross inspection demonstrated a 7-g, 2.8×2.6×1.8-cm, homogeneous, tan-pink, rubbery nodule with minimal surrounding soft tissue. Histologic examination showed a bland proliferation of spindle cells with storiform and whorled patterns (Figure 3). No notable nuclear atypia or necrosis was identified. The tumor cells were focally positive for EMA (Figure 4), claudin-1, and CD34 and negative for S-100, SOX10, GLUT1, desmin, STAT6, pankeratin AE1/AE3, and SMA. The diagnosis of perineurioma was rendered. No recurrence of the lesion was appreciated clinically on a 6-month follow-up examination.

Comment

Characteristics of Perineuriomas—On gross evaluation, perineuriomas are firm, gray-white, and well circumscribed but not encapsulated. Histologically, perineuriomas can have a storiform, whorled, or lamellar pattern of spindle cells. Perivascular whorls can be a histologic clue. The spindle cells are bland appearing and typically are elongated and slender but can appear slightly ovoid and plump. The background stroma can be myxoid, collagenous, or mixed. There usually is no atypia, and mitotic figures are rare.^2,3,6,7 Intraneural perineuriomas vary architecturally in that they display a unique onion bulb–like appearance in which whorls of cytoplasmic material of variable sizes surround central axons.³

Diagnosis—The diagnosis of perineuriomas usually requires characteristic immunohistochemical and sometimes ultrastructural features. Perineuriomas are positive for EMA and GLUT1 and variable for CD34.⁶ Approximately 20% to 91% will be positive for claudin-1, a tight junction protein associated with perineuriomas.⁸ Of note, EMA and GLUT1 usually are positive in both neoplastic and nonneoplastic perineurial cells.^9,10 Occasionally, these tumors can be focally positive for SMA and negative for S-100 and glial fibrillary acidic protein. The bipolar, thin, delicate, cytoplasmic processes with long-tapering nuclei may be easier to appreciate on electron microscopy than on conventional light microscopy. In addition, the cells contain pinocytotic vesicles and a discontinuous external lamina, which may be helpful for diagnosis.¹⁰

Genetics—Genetic alterations in perineurioma continue to be elucidated. Although many soft tissue perineuriomas possess deletion of chromosome 22q material, this is not a consistent finding and is not pathognomonic. Notably, the NF2 tumor suppressor gene is found on chromosome 22.¹¹ For the sclerosing variant of perineurioma, rearrangements or deletions of chromosome 10q have been described. A study of 14 soft tissue/extraneural perineuriomas using whole-exome sequencing and single nucleotide polymorphism array showed 6 cases of recurrent chromosome 22q deletions containing the NF2 locus and 4 cases with a previously unreported finding of chromosome 17q deletions containing the NF1 locus that were mutually exclusive events in all but 1 case.¹² Although perineuriomas can harbor NF1 or NF2 mutations, perineuriomas are not considered to be associated with neurofibromatosis type 1 or 2 (NF1 or NF2, respectively). Patients with NF1 or NF2 and perineurioma are exceedingly rare. One pediatric patient with both soft tissue perineurioma and NF1 has been reported in the literature.¹³

Differential Diagnosis—Perineuriomas should be distinguished from other benign neural neoplasms of the skin and soft tissue. Commonly considered in the differential diagnosis is schwannoma and neurofibroma. Schwannomas are encapsulated epineurial nerve sheath tumors comprised of a neoplastic proliferation of Schwann cells. Schwannomas morphologically differ from perineuriomas because of the presence of the hypercellular Antoni A with Verocay bodies and the hypocellular myxoid Antoni B patterns of spindle cells with elongated wavy nuclei and tapered ends. Other features include hyalinized vessels, hemosiderin deposition, cystic degeneration, and/or degenerative atypia.^3,14 Importantly, the constituent cells of schwannomas are positive for S-100 and SOX10 and negative for EMA.³ Neurofibromas consist of fascicles and whorls of Schwann cells in a background myxoid stroma with scattered mast cells, lymphocytes, fibroblasts, and perineurial cells. Similar to schwannomas, neurofibromas also are positive for S-100 and negative for EMA.^3,14 Neurofibromas can have either a somatic or germline mutation of the biallelic NF1 gene on chromosome 17q11.2 with subsequent loss of protein neurofibromin activity.¹⁵ Less common but still a consideration are the hybrid peripheral nerve sheath tumors that may present with a biphasic or intermingled morphology. Combinations include neurofibroma-schwannoma, schwannoma-perineurioma, and neurofibroma-perineurioma. The hybrid schwannoma-perineurioma has a mixture of thin and plump spindle cells with tapered nuclei as well as patchy S-100 positivity corresponding to schwannian areas. Similarly, S-100 will highlight the wavy Schwann cells in neurofibroma-perineurioma as well as CD34-highlighting fibroblasts.^7,15 In both aforementioned hybrid tumors, EMA will be positive in the perineurial areas. Another potential diagnostic consideration that can occur in both pediatric and adult populations is dermatofibrosarcoma protuberans (DFSP), which is comprised of a dermal proliferation of monomorphic fusiform spindle cells. Although both perineuriomas and DFSP can have a storiform architecture, DFSP is more asymmetric and infiltrative. Dermatofibrosarcoma protuberans is recognized in areas of individual adipocyte trapping, referred to as honeycombing. Dermatofibrosarcoma protuberans typically does not express EMA, though the sclerosing variant of DFSP has been reported to sometimes demonstrate focal EMA reactivity.^11,14,16 For morphologically challenging cases, cytogenetic studies will show t(17;22) translocation fusing the COL1A1 and PDGFRB genes.¹⁶ Finally, for subcutaneous or deep-seated tumors, one also may consider other mesenchymal neoplasms, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, or low-grade malignant peripheral nerve sheath tumor (MPNST).¹¹

Management—Perineuriomas are considered benign. The presence of mitotic figures, pleomorphism, and degenerative nuclear atypia akin to ancient change, as seen in ancient schwannoma, does not affect their benign clinical behavior. Treatment of a perineurioma typically is surgical excision with conservative margins and minimal chance of recurrence.^1,11 So-called malignant perineuriomas are better classified as MPNSTs with perineural differentiation or perineurial MPNST. They also are positive for EMA and may be distinguished from perineurioma by the presence of major atypia and an infiltrative growth pattern.^17,18

Considerations in the Pediatric Population—Few pediatric soft tissue perineuriomas have been reported. A clinicopathologic analysis by Hornick and Fletcher¹ of patients with soft tissue perineurioma showed that only 6 of 81 patients were younger than 20 years. The youngest reported case of perineurioma occurred as an extraneural perineurioma on the scalp in an infant.¹⁹ Only 1 soft tissue perineural MPNST has been reported in the pediatric population, arising on the face of an 11-year-old boy. In a case series of 11 pediatric perineuriomas, including extraneural and intraneural, there was no evidence of recurrence or metastasis at follow-up.⁴

Conclusion

Perineuriomas are rare benign peripheral nerve sheath tumors with unique histologic and immunohistochemical features. Soft tissue perineuriomas in the pediatric population are an important diagnostic consideration, especially for the pediatrician or dermatologist when encountering a well-circumscribed nodular soft tissue lesion of the extremity or when encountering a neural-appearing tumor in the subcutaneous tissue.

Acknowledgment—We would like to thank Christopher Fletcher, MD (Boston, Massachusetts), for his expertise in outside consultation for patient 1.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism that typically presents in infancy.¹ Although it is clinically characterized by acral and periorificial dermatitis, alopecia, and diarrhea, only 20% of cases present with this triad.² Zinc deficiency in AE can either be acquired or inborn (congenital). Acquired forms can occur from dietary inadequacy or malabsorption, whereas genetic causes are related to an autosomal-recessive disorder affecting zinc transporters.¹ We report a case of a 3-month-old female infant with acquired AE who was successfully treated with zinc supplementation over the course of 3 weeks.

Case Report

A 3-month-old female infant presented to the emergency department with a rash of 2 weeks’ duration. She was born full term with no birth complications. The patient’s mother reported that the rash started on the cheeks, then enlarged and spread to the neck, back, and perineum. The patient also had been having diarrhea during this time. She previously had received mupirocin and cephalexin with no response to treatment. Maternal history was negative for lupus, and the mother’s diet consisted of a variety of foods but not many vegetables. The patient was exclusively breastfed, and there was no pertinent history of similar rashes occurring in other family members.

Physical examination revealed the patient had annular and polycyclic, hyperkeratotic, crusted papules and plaques on the cheeks, neck, back, and axillae, as well as the perineum/groin and perianal regions (Figure 1). The differential diagnosis at the time included neonatal lupus, zinc deficiency, and syphilis. Relevant laboratory testing and a shave biopsy of the left axilla were obtained.

Comment

Etiology of AE—Acrodermatitis enteropathica was first identified in 1942 as an acral rash associated with diarrhea³; in 1973, Barnes and Moynahan⁴ discovered zinc deficiency as a causal agent for these findings. The causes of AE are further subclassified as either an acquired or inborn etiology. Congenital causes commonly are seen in infants within the first few months of life, whereas acquired forms are seen at any age. Acquired forms in infants can occur from failure of the mother to secrete zinc in breast milk, low maternal serum zinc levels, or other reasons causing low nutritional intake. A single mutation in the SLC30A2 gene has been found to markedly reduce zinc concentrations in breast milk, thus causing zinc deficiency in breastfed infants.⁵ Other acquired forms can be caused by malabsorption, sometimes after surgery such as intestinal bypass or from intravenous nutrition without sufficient zinc.¹ The congenital form of AE is an autosomal-recessive disorder occurring from mutations in the SLC39A4 gene located on band 8q24.3. Affected individuals have a decreased ability to absorb zinc in the small intestine because of defects in zinc transporters ZIP and ZnT.⁶ Based on our patient’s laboratory findings and history, it is believed that the zinc deficiency was acquired, as the condition normalized with repletion and has not required any supplementation in the year of follow-up. In addition, the absence of a pertinent family history supported an acquired diagnosis, which has various etiologies, whereas the congenital form primarily is a genetic disease.

Diagnosis of AE—The characteristic clinical features of AE include erythematous, dry, scaly papules and plaques that may evolve into crusted, erosive, pustular lesions. These lesions typically are distributed in a periorificial and acral pattern.^1,2 Although AE includes the clinical triad of acral and periorificial dermatitis, alopecia, and diarrhea, most cases present with only partial features of this syndrome, as seen in our patient, who presented with only 2 symptoms—dermatitis and diarrhea. The diagnosis of AE is based on clinical and laboratory abnormalities, especially a low serum zinc level. Low levels of zinc-dependent enzymes, such as alkaline phosphatase, may support the diagnosis, as seen in our patient. Histologic evaluation is characteristic but is not diagnostic, as the same findings can be seen in other nutritional disorders. Such findings include confluent parakeratosis associated with a reduced granular layer in early lesions and subsequent ballooning of subcorneal keratinocytes, upper epidermal pallor, and intraepidermal clefts. Late lesions exhibit psoriasiform hyperplasia of the epidermis with less epidermal pallor.⁷

Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.¹ Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.² Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD²; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).^3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.⁵ In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.⁴ Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.⁶ Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.^7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.⁴ Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.⁹

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.⁶ Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.¹⁰ Other causes of PTCD include tar products and certain medications.¹¹ Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.⁶ Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.^14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.¹⁵ A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.^16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.^16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.¹⁶ These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.¹⁸

In the largest and most recent PPT series from North America (1999-2009),² sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.^19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.^2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.^19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.²⁴ In the most recent NACDG patch test data, MI was the second most common contact allergen.²⁵ Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.²⁶ In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.^26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.^25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.³³ Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.^2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.^36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.^40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.²

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.^2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.⁴⁴

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.⁴⁵ Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.⁴

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.⁴

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.¹ Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.² Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD²; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).^3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.⁵ In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.⁴ Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.⁶ Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.^7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.⁴ Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.⁹

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.⁶ Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.¹⁰ Other causes of PTCD include tar products and certain medications.¹¹ Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.⁶ Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.^14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.¹⁵ A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.^16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.^16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.¹⁶ These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.¹⁸

In the largest and most recent PPT series from North America (1999-2009),² sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.^19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.^2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.^19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.²⁴ In the most recent NACDG patch test data, MI was the second most common contact allergen.²⁵ Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.²⁶ In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.^26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.^25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.³³ Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.^2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.^36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.^40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.²

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.^2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.⁴⁴

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.⁴⁵ Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.⁴

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.⁴

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.¹ Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.² Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD²; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).^3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.⁵ In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.⁴ Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.⁶ Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.^7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.⁴ Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.⁹

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.⁶ Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.¹⁰ Other causes of PTCD include tar products and certain medications.¹¹ Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.⁶ Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.^14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.¹⁵ A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.^16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.^16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.¹⁶ These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.¹⁸

In the largest and most recent PPT series from North America (1999-2009),² sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.^19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.^2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.^19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.²⁴ In the most recent NACDG patch test data, MI was the second most common contact allergen.²⁵ Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.²⁶ In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.^26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.^25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.³³ Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.^2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.^36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.^40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.²

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.^2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.⁴⁴

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.⁴⁵ Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.⁴

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.⁴

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.¹ Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.²

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion³:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.⁴

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.⁵Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.⁶Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.⁴

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.⁷

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.^8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.⁹

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.¹⁰In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.⁹The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.¹¹ The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.¹² In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.¹³

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.¹⁴

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.^6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.