Contact Dermatitis

One of the perils of patch testing is fielding questions about which type of allergens will be used. Patients often ask if the patch test includes milk, foods, dander, mold, pets, and grass. Most patch testers spend a substantial amount of time explaining that the purpose of patch testing is to detect applied chemical allergens: It’s not what you eat; rather, it’s what touches your skin. However, the big caveat is that some oral, parenteral, inhaled, and even cutaneous allergens can produce systemic contact dermatitis (SCD), which represents a unique clinical scenario that we will review in this month’s Final Interpretation column.

There are many patterns of SCD. Familiarity with potential clinical presentations can aid in diagnosis and counseling. Systemic contact dermatitis tends to be symmetrical. Dyshidrotic hand dermatitis is a reported pattern for systemic metal allergy, most commonly nickel. Refractory eyelid or genital dermatitis can reflect a systemic exposure, particularly if the dermatitis is in areas not caused by direct skin contact with the allergen. Systemic drug-related intertriginous and flexural exanthema is, as the name describes, an eruption involving axillae, genital skin, and flexural sites. It usually is a type of drug reaction, but the culprit can be an ingested allergen. So-called baboon syndrome SCD can cause persistent genital and intertriginous dermatitis. Other clues to SCD include dermatitis flare at the patch test site and erythema multiforme. Some patients also describe systemic symptoms, including headache, fatigue, and malaise.

Rhus Dermatitis

Poison ivy is the most common cause of acute contact dermatitis but also can be a cause of SCD. From the family Anacardiaceae, this sneaky plant is common in many parts of the United States; most allergic patients are familiar with their allergy from prior exposure.

In 1982, 54 Little League baseball attendees developed diffuse vesicular dermatitis involving the flexures after ingesting packaged cashews contaminated with cashew shells.¹ In the same family as poison ivy, the cashew nut tree (Anacardium occidentale) produces a cashew apple containing the cashew nut. The cashew shell is the site that contains the allergenic oils. Typically, cashews are processed to remove the shell and oil prior to consumption. Ingestion of raw cashews is more likely to lead to SCD than roasted cashews because the heat in the roasting process can break down any allergenic oil.²

Metals

Systemic exposures to nickel usually are dietary. Clinically, SCD from nickel most commonly presents as refractory dyshidrotic hand eczema or papular elbow dermatitis.³ Nickel is commonly found in vitamins and supplements as well as certain whole grains, vegetables, beans, coffee, chocolate, and tea.⁴ Sometimes, cookware also can be a source of nickel exposure, particularly with steel cookware, from which nickel can leach into food.

In general, a diet lower than 150 μg/d is needed to prevent flares.⁵ A point-based diet is available for nickel-allergic patients.⁵ Patients should ingest a restricted amount of nickel (15 points daily); those who are extremely allergic might need to limit nickel ingestion to less than 5 points daily. Because of the challenges associated with maintaining a low-nickel diet, chelation therapy has been recommended to prevent nickel absorption. Disulfiram³ and ascorbic acid⁵ have been recommended, but larger studies are lacking.

Cobalt and chromium are other metals that, when ingested, can lead to SCD; both can be found in multivitamins. Other sources of dietary chromium include vegetables, coffee, beans, certain meats, and seafood.⁴ For cobalt, the dietary exposures are similar with the addition of nuts, apricots, and whole-grain flour. A point-based cobalt avoidance diet has been published. This diet recommends less than 12 μg of cobalt daily; patients can ingest up to 12 cobalt points daily.⁶

Likewise, gold has been reported to cause SCD, with one case attributed to gold in a homeopathic cardiac medication.⁷ Gold SCD also should be considered in the setting of ingested gold-containing alcoholic beverages and historically has been associated with intramuscular gold sodium thiomalate for the treatment of rheumatoid arthritis.⁸

Metal implants, including prosthetic joints, stents, and other devices, have been implicated in SCD. (More to come on this topic soon; yes, dear reader, that is a teaser!)

Fragrances

Balsam of Peru
Secreted by the tree Myroxylon balsamum var pereirae, balsam of Peru (BOP) contains several potential allergens, including cinnamon oils (eg, eugenol, vanillin, cinnamates), coniferin derivatives, and benzoic acid derivatives.⁹ Foods and beverages associated with BOP include citrus, pickled vegetables, chocolate, ice cream, chili, pizza, tomatoes, wine, beer, gin, vermouth, flavored tea, and soft drinks.¹⁰ Flavoring agents, spices (eg, cloves, curry, vanilla, cinnamon, allspice, ginger, anise), and condiments (eg, ketchup, barbeque sauce) are potential sources, as are cough medicines, lozenges, and flavored tobacco.

Salam and Fowler¹⁰ described BOP-allergic patients whose condition improved with dietary restriction of BOP. Avoidance of tomatoes, citrus, spices, and cola most commonly contributed to improvement.¹⁰ Scheman et al⁹ proposed BOP subgroups, including the eugenol, vanillin, cinnamate, benzoate, ferulic acid, and coniferin groups. Targeted patch testing can identify relevant subgroups, and patients can focus dietary restrictions by subgroup.

Plants
Systemic contact dermatitis has been reported in association with a number of plants and herbals, including chamomile in tea,¹¹ goldenrod in a medicated extract,¹²Hosta plantaginea roots,¹³ and garlic extract for hyperlipidemia.¹⁴ Many more have been described.

Propolis
Also known as bee glue, propolis comprises a mixture of balsams, resins, waxes, essential oils, pollen, cinnamic alcohol, and vitamins. It can be found in many cosmetic products, foods, and chewing gum.¹⁵ Propolis has been reported to be the source of SCD from ingestion of propolis capsules, which have been used to promote immune stimulation,¹⁵ and propolis solution as a natural tonic.¹⁶

Propylene Glycol

Propylene glycol (PG) can be found in (believe it or not) foods and medications. In foods, it typically is used for its softening, humectant, and preservative properties.¹⁷ Common food sources of PG include sauces, desserts, snack foods, and salad dressings.

Many topical prescription medications, including corticosteroids and newer nonsteroidal anti-inflammatory topicals, might contain PG; providers must specifically request PG-free products for PG-allergic patients. A detailed PG-avoidance diet lists products to avoid and products that are PG free.¹⁸

Preservatives

Sulfites
These compounds are preservatives found in cosmetics, hair dyes, and certain foods. Systemic contact dermatitis caused by sulfites in food has been described in numerous patients. One unfortunate vacationer developed axillary and groin dermatitis after ingesting large amounts of grapes, wine, shrimp, and french fries while vacationing in Italy.¹⁹ Among dietary sources, beer and wine contain higher levels of sulfites. Sulfites also can be found in some pickled foods; bottled citrus juice; dried fruits; and commercial prepared foods, such as powdered potatoes and gravy mixes. Other reports of SCD from sulfites include an enema preparation²⁰ and anesthetics²¹ as the source of the allergen.

Formaldehyde
Formaldehyde can cause SCD after ingestion of aspartame, which is hydrolyzed to phenylalanine, aspartic acid, and aspartic acid methyl ester in the intestine.²² The methyl ester is converted to methyl alcohol, which is transported to the liver and oxidized to formaldehyde, which is then converted to formic acid. Hill and Belsito²² reported a case of SCD presenting as eyelid dermatitis after ingestion of an aspartame-based artificial sweetener. A similar case of eyelid, neck, and leg dermatitis was reported after ingestion of drinks and candy sweetened with aspartame.²³

Parabens
Although parabens are rare contact sensitizers, there are a few reports of paraben SCD. Cases include a predominantly flexural pattern from ingestion of a mucolytic-containing methylparaben,²⁴ a generalized eczematous eruption after intramuscular injection of ampicillin preserved with methylparaben and propylparaben,²⁵ and diffuse dermatitis from methylparaben in a local anesthetic.²⁶

Sorbic Acid
Sorbic acid is utilized as a preservative in foods and occurs naturally in red fruit, such as strawberries and cranberries.²⁷ It is a rare allergen, but several cases of sorbic acid SCD have been reported, including perianal and buttock dermatitis,²⁷ hand dermatitis in an infant,²⁸ and hand-and-foot dermatitis in a storekeeper.²⁹

Carmine

Carmine, or cochineal extract, is a red dye derived from dried pulverized scale insects of the family Coccidae. This chemical can be used in a multitude of foods and medications, including candies, yogurt, red velvet items, popsicles, food coloring, frozen meat and fish, ice cream, syrups, ketchup, sausage, donuts, cake pops, applesauce, canned fruits, soups, and drinks.³⁰ Machler and Jacob³¹ described a child with recurrent episodes of erythroderma and periorbital edema in whom patch testing revealed a reaction to carmine. The patient’s mother connected the flares with ingestion of red velvet cupcakes.³¹ Ferris et al³² reported a likely case of SCD attributed to carmine in a multivitamin.

Steroids

Ingested and injected corticosteroids have been associated with SCD, which is illustrated by a case of a generalized cutaneous eruption several days after joint injection with triamcinolone acetonide.³³ In another report, a patient developed an eruption in the body folds, later generalized, after topical application of a corticosteroid, first in ear drops and later in nasal spray.³⁴ Traditional corticosteroid classification systems might be less reliable in predicting relevant allergens in corticosteroid SCD; comprehensive testing, including oral challenge, might be necessary to identify alternatives.³³

Ethylenediamine

Ethylenediamine is an uncommon allergen in patch test populations. It is present in aminophylline³⁵ and is utilized in the production of hydroxyzine³⁶ and other piperazine-derived medications, such as cetirizine, levocetirizine, meclizine, and olanzapine. Several cases of SCD caused by aminophylline,³⁵ cetirizine,³⁶ and hydroxyzine³⁷ have been reported, all in the setting of a positive patch test reaction to ethylenediamine.

When to Counsel About Systemic Exposures

In general, we usually do not counsel on systemic exposures to allergens at the final patch test reading unless the pattern of dermatitis or clinical history strongly suggests systemic exposure. In most cases, we find that counseling on topical allergen avoidance alone is sufficient to treat allergic contact dermatitis. Because of the restrictive nature of allergen-avoidance diets, counseling all patients on the potential for SCD might cause undue stress without much benefit. However, if a patient experiences persistent dermatitis on follow-up with topical avoidance alone, we often will delve into systemic exposures and counsel on further avoidance strategies, including medication and diet.

Final Interpretation

A multitude of chemicals have been reported as the source of SCD; these exposures can occur through ingestion, injection, and inhaled and cutaneous routes. Chemicals present in foods, medications, and beverages have been implicated. Systemic contact dermatitis is rare and should be considered when traditional avoidance of contact allergens is unsuccessful and the clinical pattern is consistent with SCD.

One of the perils of patch testing is fielding questions about which type of allergens will be used. Patients often ask if the patch test includes milk, foods, dander, mold, pets, and grass. Most patch testers spend a substantial amount of time explaining that the purpose of patch testing is to detect applied chemical allergens: It’s not what you eat; rather, it’s what touches your skin. However, the big caveat is that some oral, parenteral, inhaled, and even cutaneous allergens can produce systemic contact dermatitis (SCD), which represents a unique clinical scenario that we will review in this month’s Final Interpretation column.

There are many patterns of SCD. Familiarity with potential clinical presentations can aid in diagnosis and counseling. Systemic contact dermatitis tends to be symmetrical. Dyshidrotic hand dermatitis is a reported pattern for systemic metal allergy, most commonly nickel. Refractory eyelid or genital dermatitis can reflect a systemic exposure, particularly if the dermatitis is in areas not caused by direct skin contact with the allergen. Systemic drug-related intertriginous and flexural exanthema is, as the name describes, an eruption involving axillae, genital skin, and flexural sites. It usually is a type of drug reaction, but the culprit can be an ingested allergen. So-called baboon syndrome SCD can cause persistent genital and intertriginous dermatitis. Other clues to SCD include dermatitis flare at the patch test site and erythema multiforme. Some patients also describe systemic symptoms, including headache, fatigue, and malaise.

Rhus Dermatitis

Poison ivy is the most common cause of acute contact dermatitis but also can be a cause of SCD. From the family Anacardiaceae, this sneaky plant is common in many parts of the United States; most allergic patients are familiar with their allergy from prior exposure.

In 1982, 54 Little League baseball attendees developed diffuse vesicular dermatitis involving the flexures after ingesting packaged cashews contaminated with cashew shells.¹ In the same family as poison ivy, the cashew nut tree (Anacardium occidentale) produces a cashew apple containing the cashew nut. The cashew shell is the site that contains the allergenic oils. Typically, cashews are processed to remove the shell and oil prior to consumption. Ingestion of raw cashews is more likely to lead to SCD than roasted cashews because the heat in the roasting process can break down any allergenic oil.²

Metals

Systemic exposures to nickel usually are dietary. Clinically, SCD from nickel most commonly presents as refractory dyshidrotic hand eczema or papular elbow dermatitis.³ Nickel is commonly found in vitamins and supplements as well as certain whole grains, vegetables, beans, coffee, chocolate, and tea.⁴ Sometimes, cookware also can be a source of nickel exposure, particularly with steel cookware, from which nickel can leach into food.

In general, a diet lower than 150 μg/d is needed to prevent flares.⁵ A point-based diet is available for nickel-allergic patients.⁵ Patients should ingest a restricted amount of nickel (15 points daily); those who are extremely allergic might need to limit nickel ingestion to less than 5 points daily. Because of the challenges associated with maintaining a low-nickel diet, chelation therapy has been recommended to prevent nickel absorption. Disulfiram³ and ascorbic acid⁵ have been recommended, but larger studies are lacking.

Cobalt and chromium are other metals that, when ingested, can lead to SCD; both can be found in multivitamins. Other sources of dietary chromium include vegetables, coffee, beans, certain meats, and seafood.⁴ For cobalt, the dietary exposures are similar with the addition of nuts, apricots, and whole-grain flour. A point-based cobalt avoidance diet has been published. This diet recommends less than 12 μg of cobalt daily; patients can ingest up to 12 cobalt points daily.⁶

Likewise, gold has been reported to cause SCD, with one case attributed to gold in a homeopathic cardiac medication.⁷ Gold SCD also should be considered in the setting of ingested gold-containing alcoholic beverages and historically has been associated with intramuscular gold sodium thiomalate for the treatment of rheumatoid arthritis.⁸

Metal implants, including prosthetic joints, stents, and other devices, have been implicated in SCD. (More to come on this topic soon; yes, dear reader, that is a teaser!)

Fragrances

Balsam of Peru
Secreted by the tree Myroxylon balsamum var pereirae, balsam of Peru (BOP) contains several potential allergens, including cinnamon oils (eg, eugenol, vanillin, cinnamates), coniferin derivatives, and benzoic acid derivatives.⁹ Foods and beverages associated with BOP include citrus, pickled vegetables, chocolate, ice cream, chili, pizza, tomatoes, wine, beer, gin, vermouth, flavored tea, and soft drinks.¹⁰ Flavoring agents, spices (eg, cloves, curry, vanilla, cinnamon, allspice, ginger, anise), and condiments (eg, ketchup, barbeque sauce) are potential sources, as are cough medicines, lozenges, and flavored tobacco.

Salam and Fowler¹⁰ described BOP-allergic patients whose condition improved with dietary restriction of BOP. Avoidance of tomatoes, citrus, spices, and cola most commonly contributed to improvement.¹⁰ Scheman et al⁹ proposed BOP subgroups, including the eugenol, vanillin, cinnamate, benzoate, ferulic acid, and coniferin groups. Targeted patch testing can identify relevant subgroups, and patients can focus dietary restrictions by subgroup.

Plants
Systemic contact dermatitis has been reported in association with a number of plants and herbals, including chamomile in tea,¹¹ goldenrod in a medicated extract,¹²Hosta plantaginea roots,¹³ and garlic extract for hyperlipidemia.¹⁴ Many more have been described.

Propolis
Also known as bee glue, propolis comprises a mixture of balsams, resins, waxes, essential oils, pollen, cinnamic alcohol, and vitamins. It can be found in many cosmetic products, foods, and chewing gum.¹⁵ Propolis has been reported to be the source of SCD from ingestion of propolis capsules, which have been used to promote immune stimulation,¹⁵ and propolis solution as a natural tonic.¹⁶

Propylene Glycol

Propylene glycol (PG) can be found in (believe it or not) foods and medications. In foods, it typically is used for its softening, humectant, and preservative properties.¹⁷ Common food sources of PG include sauces, desserts, snack foods, and salad dressings.

Many topical prescription medications, including corticosteroids and newer nonsteroidal anti-inflammatory topicals, might contain PG; providers must specifically request PG-free products for PG-allergic patients. A detailed PG-avoidance diet lists products to avoid and products that are PG free.¹⁸

Preservatives

Sulfites
These compounds are preservatives found in cosmetics, hair dyes, and certain foods. Systemic contact dermatitis caused by sulfites in food has been described in numerous patients. One unfortunate vacationer developed axillary and groin dermatitis after ingesting large amounts of grapes, wine, shrimp, and french fries while vacationing in Italy.¹⁹ Among dietary sources, beer and wine contain higher levels of sulfites. Sulfites also can be found in some pickled foods; bottled citrus juice; dried fruits; and commercial prepared foods, such as powdered potatoes and gravy mixes. Other reports of SCD from sulfites include an enema preparation²⁰ and anesthetics²¹ as the source of the allergen.

Formaldehyde
Formaldehyde can cause SCD after ingestion of aspartame, which is hydrolyzed to phenylalanine, aspartic acid, and aspartic acid methyl ester in the intestine.²² The methyl ester is converted to methyl alcohol, which is transported to the liver and oxidized to formaldehyde, which is then converted to formic acid. Hill and Belsito²² reported a case of SCD presenting as eyelid dermatitis after ingestion of an aspartame-based artificial sweetener. A similar case of eyelid, neck, and leg dermatitis was reported after ingestion of drinks and candy sweetened with aspartame.²³

Parabens
Although parabens are rare contact sensitizers, there are a few reports of paraben SCD. Cases include a predominantly flexural pattern from ingestion of a mucolytic-containing methylparaben,²⁴ a generalized eczematous eruption after intramuscular injection of ampicillin preserved with methylparaben and propylparaben,²⁵ and diffuse dermatitis from methylparaben in a local anesthetic.²⁶

Sorbic Acid
Sorbic acid is utilized as a preservative in foods and occurs naturally in red fruit, such as strawberries and cranberries.²⁷ It is a rare allergen, but several cases of sorbic acid SCD have been reported, including perianal and buttock dermatitis,²⁷ hand dermatitis in an infant,²⁸ and hand-and-foot dermatitis in a storekeeper.²⁹

Carmine

Carmine, or cochineal extract, is a red dye derived from dried pulverized scale insects of the family Coccidae. This chemical can be used in a multitude of foods and medications, including candies, yogurt, red velvet items, popsicles, food coloring, frozen meat and fish, ice cream, syrups, ketchup, sausage, donuts, cake pops, applesauce, canned fruits, soups, and drinks.³⁰ Machler and Jacob³¹ described a child with recurrent episodes of erythroderma and periorbital edema in whom patch testing revealed a reaction to carmine. The patient’s mother connected the flares with ingestion of red velvet cupcakes.³¹ Ferris et al³² reported a likely case of SCD attributed to carmine in a multivitamin.

Steroids

Ingested and injected corticosteroids have been associated with SCD, which is illustrated by a case of a generalized cutaneous eruption several days after joint injection with triamcinolone acetonide.³³ In another report, a patient developed an eruption in the body folds, later generalized, after topical application of a corticosteroid, first in ear drops and later in nasal spray.³⁴ Traditional corticosteroid classification systems might be less reliable in predicting relevant allergens in corticosteroid SCD; comprehensive testing, including oral challenge, might be necessary to identify alternatives.³³

Ethylenediamine

Ethylenediamine is an uncommon allergen in patch test populations. It is present in aminophylline³⁵ and is utilized in the production of hydroxyzine³⁶ and other piperazine-derived medications, such as cetirizine, levocetirizine, meclizine, and olanzapine. Several cases of SCD caused by aminophylline,³⁵ cetirizine,³⁶ and hydroxyzine³⁷ have been reported, all in the setting of a positive patch test reaction to ethylenediamine.

When to Counsel About Systemic Exposures

In general, we usually do not counsel on systemic exposures to allergens at the final patch test reading unless the pattern of dermatitis or clinical history strongly suggests systemic exposure. In most cases, we find that counseling on topical allergen avoidance alone is sufficient to treat allergic contact dermatitis. Because of the restrictive nature of allergen-avoidance diets, counseling all patients on the potential for SCD might cause undue stress without much benefit. However, if a patient experiences persistent dermatitis on follow-up with topical avoidance alone, we often will delve into systemic exposures and counsel on further avoidance strategies, including medication and diet.

Final Interpretation

A multitude of chemicals have been reported as the source of SCD; these exposures can occur through ingestion, injection, and inhaled and cutaneous routes. Chemicals present in foods, medications, and beverages have been implicated. Systemic contact dermatitis is rare and should be considered when traditional avoidance of contact allergens is unsuccessful and the clinical pattern is consistent with SCD.

One of the perils of patch testing is fielding questions about which type of allergens will be used. Patients often ask if the patch test includes milk, foods, dander, mold, pets, and grass. Most patch testers spend a substantial amount of time explaining that the purpose of patch testing is to detect applied chemical allergens: It’s not what you eat; rather, it’s what touches your skin. However, the big caveat is that some oral, parenteral, inhaled, and even cutaneous allergens can produce systemic contact dermatitis (SCD), which represents a unique clinical scenario that we will review in this month’s Final Interpretation column.

There are many patterns of SCD. Familiarity with potential clinical presentations can aid in diagnosis and counseling. Systemic contact dermatitis tends to be symmetrical. Dyshidrotic hand dermatitis is a reported pattern for systemic metal allergy, most commonly nickel. Refractory eyelid or genital dermatitis can reflect a systemic exposure, particularly if the dermatitis is in areas not caused by direct skin contact with the allergen. Systemic drug-related intertriginous and flexural exanthema is, as the name describes, an eruption involving axillae, genital skin, and flexural sites. It usually is a type of drug reaction, but the culprit can be an ingested allergen. So-called baboon syndrome SCD can cause persistent genital and intertriginous dermatitis. Other clues to SCD include dermatitis flare at the patch test site and erythema multiforme. Some patients also describe systemic symptoms, including headache, fatigue, and malaise.

Rhus Dermatitis

Poison ivy is the most common cause of acute contact dermatitis but also can be a cause of SCD. From the family Anacardiaceae, this sneaky plant is common in many parts of the United States; most allergic patients are familiar with their allergy from prior exposure.

In 1982, 54 Little League baseball attendees developed diffuse vesicular dermatitis involving the flexures after ingesting packaged cashews contaminated with cashew shells.¹ In the same family as poison ivy, the cashew nut tree (Anacardium occidentale) produces a cashew apple containing the cashew nut. The cashew shell is the site that contains the allergenic oils. Typically, cashews are processed to remove the shell and oil prior to consumption. Ingestion of raw cashews is more likely to lead to SCD than roasted cashews because the heat in the roasting process can break down any allergenic oil.²

Metals

Systemic exposures to nickel usually are dietary. Clinically, SCD from nickel most commonly presents as refractory dyshidrotic hand eczema or papular elbow dermatitis.³ Nickel is commonly found in vitamins and supplements as well as certain whole grains, vegetables, beans, coffee, chocolate, and tea.⁴ Sometimes, cookware also can be a source of nickel exposure, particularly with steel cookware, from which nickel can leach into food.

In general, a diet lower than 150 μg/d is needed to prevent flares.⁵ A point-based diet is available for nickel-allergic patients.⁵ Patients should ingest a restricted amount of nickel (15 points daily); those who are extremely allergic might need to limit nickel ingestion to less than 5 points daily. Because of the challenges associated with maintaining a low-nickel diet, chelation therapy has been recommended to prevent nickel absorption. Disulfiram³ and ascorbic acid⁵ have been recommended, but larger studies are lacking.

Cobalt and chromium are other metals that, when ingested, can lead to SCD; both can be found in multivitamins. Other sources of dietary chromium include vegetables, coffee, beans, certain meats, and seafood.⁴ For cobalt, the dietary exposures are similar with the addition of nuts, apricots, and whole-grain flour. A point-based cobalt avoidance diet has been published. This diet recommends less than 12 μg of cobalt daily; patients can ingest up to 12 cobalt points daily.⁶

Likewise, gold has been reported to cause SCD, with one case attributed to gold in a homeopathic cardiac medication.⁷ Gold SCD also should be considered in the setting of ingested gold-containing alcoholic beverages and historically has been associated with intramuscular gold sodium thiomalate for the treatment of rheumatoid arthritis.⁸

Metal implants, including prosthetic joints, stents, and other devices, have been implicated in SCD. (More to come on this topic soon; yes, dear reader, that is a teaser!)

Fragrances

Balsam of Peru
Secreted by the tree Myroxylon balsamum var pereirae, balsam of Peru (BOP) contains several potential allergens, including cinnamon oils (eg, eugenol, vanillin, cinnamates), coniferin derivatives, and benzoic acid derivatives.⁹ Foods and beverages associated with BOP include citrus, pickled vegetables, chocolate, ice cream, chili, pizza, tomatoes, wine, beer, gin, vermouth, flavored tea, and soft drinks.¹⁰ Flavoring agents, spices (eg, cloves, curry, vanilla, cinnamon, allspice, ginger, anise), and condiments (eg, ketchup, barbeque sauce) are potential sources, as are cough medicines, lozenges, and flavored tobacco.

Salam and Fowler¹⁰ described BOP-allergic patients whose condition improved with dietary restriction of BOP. Avoidance of tomatoes, citrus, spices, and cola most commonly contributed to improvement.¹⁰ Scheman et al⁹ proposed BOP subgroups, including the eugenol, vanillin, cinnamate, benzoate, ferulic acid, and coniferin groups. Targeted patch testing can identify relevant subgroups, and patients can focus dietary restrictions by subgroup.

Plants
Systemic contact dermatitis has been reported in association with a number of plants and herbals, including chamomile in tea,¹¹ goldenrod in a medicated extract,¹²Hosta plantaginea roots,¹³ and garlic extract for hyperlipidemia.¹⁴ Many more have been described.

Propolis
Also known as bee glue, propolis comprises a mixture of balsams, resins, waxes, essential oils, pollen, cinnamic alcohol, and vitamins. It can be found in many cosmetic products, foods, and chewing gum.¹⁵ Propolis has been reported to be the source of SCD from ingestion of propolis capsules, which have been used to promote immune stimulation,¹⁵ and propolis solution as a natural tonic.¹⁶

Propylene Glycol

Propylene glycol (PG) can be found in (believe it or not) foods and medications. In foods, it typically is used for its softening, humectant, and preservative properties.¹⁷ Common food sources of PG include sauces, desserts, snack foods, and salad dressings.

Many topical prescription medications, including corticosteroids and newer nonsteroidal anti-inflammatory topicals, might contain PG; providers must specifically request PG-free products for PG-allergic patients. A detailed PG-avoidance diet lists products to avoid and products that are PG free.¹⁸

Preservatives

Sulfites
These compounds are preservatives found in cosmetics, hair dyes, and certain foods. Systemic contact dermatitis caused by sulfites in food has been described in numerous patients. One unfortunate vacationer developed axillary and groin dermatitis after ingesting large amounts of grapes, wine, shrimp, and french fries while vacationing in Italy.¹⁹ Among dietary sources, beer and wine contain higher levels of sulfites. Sulfites also can be found in some pickled foods; bottled citrus juice; dried fruits; and commercial prepared foods, such as powdered potatoes and gravy mixes. Other reports of SCD from sulfites include an enema preparation²⁰ and anesthetics²¹ as the source of the allergen.

Formaldehyde
Formaldehyde can cause SCD after ingestion of aspartame, which is hydrolyzed to phenylalanine, aspartic acid, and aspartic acid methyl ester in the intestine.²² The methyl ester is converted to methyl alcohol, which is transported to the liver and oxidized to formaldehyde, which is then converted to formic acid. Hill and Belsito²² reported a case of SCD presenting as eyelid dermatitis after ingestion of an aspartame-based artificial sweetener. A similar case of eyelid, neck, and leg dermatitis was reported after ingestion of drinks and candy sweetened with aspartame.²³

Parabens
Although parabens are rare contact sensitizers, there are a few reports of paraben SCD. Cases include a predominantly flexural pattern from ingestion of a mucolytic-containing methylparaben,²⁴ a generalized eczematous eruption after intramuscular injection of ampicillin preserved with methylparaben and propylparaben,²⁵ and diffuse dermatitis from methylparaben in a local anesthetic.²⁶

Sorbic Acid
Sorbic acid is utilized as a preservative in foods and occurs naturally in red fruit, such as strawberries and cranberries.²⁷ It is a rare allergen, but several cases of sorbic acid SCD have been reported, including perianal and buttock dermatitis,²⁷ hand dermatitis in an infant,²⁸ and hand-and-foot dermatitis in a storekeeper.²⁹

Carmine

Carmine, or cochineal extract, is a red dye derived from dried pulverized scale insects of the family Coccidae. This chemical can be used in a multitude of foods and medications, including candies, yogurt, red velvet items, popsicles, food coloring, frozen meat and fish, ice cream, syrups, ketchup, sausage, donuts, cake pops, applesauce, canned fruits, soups, and drinks.³⁰ Machler and Jacob³¹ described a child with recurrent episodes of erythroderma and periorbital edema in whom patch testing revealed a reaction to carmine. The patient’s mother connected the flares with ingestion of red velvet cupcakes.³¹ Ferris et al³² reported a likely case of SCD attributed to carmine in a multivitamin.

Steroids

Ingested and injected corticosteroids have been associated with SCD, which is illustrated by a case of a generalized cutaneous eruption several days after joint injection with triamcinolone acetonide.³³ In another report, a patient developed an eruption in the body folds, later generalized, after topical application of a corticosteroid, first in ear drops and later in nasal spray.³⁴ Traditional corticosteroid classification systems might be less reliable in predicting relevant allergens in corticosteroid SCD; comprehensive testing, including oral challenge, might be necessary to identify alternatives.³³

Ethylenediamine

Ethylenediamine is an uncommon allergen in patch test populations. It is present in aminophylline³⁵ and is utilized in the production of hydroxyzine³⁶ and other piperazine-derived medications, such as cetirizine, levocetirizine, meclizine, and olanzapine. Several cases of SCD caused by aminophylline,³⁵ cetirizine,³⁶ and hydroxyzine³⁷ have been reported, all in the setting of a positive patch test reaction to ethylenediamine.

When to Counsel About Systemic Exposures

In general, we usually do not counsel on systemic exposures to allergens at the final patch test reading unless the pattern of dermatitis or clinical history strongly suggests systemic exposure. In most cases, we find that counseling on topical allergen avoidance alone is sufficient to treat allergic contact dermatitis. Because of the restrictive nature of allergen-avoidance diets, counseling all patients on the potential for SCD might cause undue stress without much benefit. However, if a patient experiences persistent dermatitis on follow-up with topical avoidance alone, we often will delve into systemic exposures and counsel on further avoidance strategies, including medication and diet.

Final Interpretation

A multitude of chemicals have been reported as the source of SCD; these exposures can occur through ingestion, injection, and inhaled and cutaneous routes. Chemicals present in foods, medications, and beverages have been implicated. Systemic contact dermatitis is rare and should be considered when traditional avoidance of contact allergens is unsuccessful and the clinical pattern is consistent with SCD.

The pediatric population has a unique product exposure profile due to the many care products specifically marketed for use in children. In fact, the prevalence of allergic contact dermatitis (ACD) in children may be as high as 24.5% in the United States.¹ In patch tested children, relevant positive reaction rates of 56.7% and 48% have been reported by the North American Contact Dermatitis Group and the Pediatric Contact Dermatitis Registry, respectively.^2,3 In this article, we provide an overview of current trends in pediatric patch testing as well as specific considerations in this patient population.

Patch Test Reactions in Children

Several publications have documented pediatric patch test reactions. The North American Contact Dermatitis Group reported patch test results in 883 children from the United States and Canada (2005-2012).² The most common reactions were nickel (28.1%), cobalt (12.3%), neomycin (7.1%), balsam of Peru (5.7%), lanolin (5.5%), and fragrance mix I (5.2%). When compared to adults, children were more likely to have relevant positive patch tests to nickel, cobalt, and compositae mix.² In comparison, data from the Pediatric Contact Dermatitis Registry showed that the most common reactions in 1142 children in the United States (2015-2016) were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), and propylene glycol (6.8%).³

Allergen sensitivities may vary based on geographic region. In Spain, children showed the highest sensitivities to thiomersal (10.2%), cobalt (9.1%), colophony (9.1%), paraphenylenediamine (8.3%), mercury (7.9%), potassium dichromate (7.9%), and nickel (6.4%).⁴

Pediatric Patch Testing Pearls

History of Product Use
From diapers to drama club, pediatric exposures and sources of ACD are not the same as those seen in adults. Because obtaining a medical history from a toddler can be exasperating, the patient’s caregivers should be asked about potential exposures, ranging from personal care products and diapers to school activities, hobbies, and sports.^5,6 It is important to keep in mind that the patient’s primary caregiver may not be the only individual who applies products to the child.⁷

Application of Allergens
Children are not merely small adults, but they usually do have smaller backs than adult patients. This reduced surface area means that the patch tester must carefully select the allergens to be patch tested. For reference, the back of a typical 6-year-old child can fit 40 to 60 allergens during patch testing.⁸

Patch Test Chambers
In children, the use of plastic patch test chambers may be preferred over aluminum chambers. Children with persistent pruritic subcutaneous nodules induced by aluminum-based vaccines also may have delayed-type sensitivity reactions to aluminum.⁹ These patients could react to the aluminum present in some patch test chambers, making interpretation of the results difficult. The authors (A.R.A. and M.R.) typically use plastic chambers in the pediatric population.

Managing Expectations
As with other procedures in the pediatric population, patch testing can elicit emotions of fear, anxiety, and distrust. Video distraction and/or role-playing games may help capture the attention of children and can be particularly helpful during patch application. Children may be apprehensive about the term allergy testing if they are familiar with the term needle testing from previous allergies.⁵

Securing Patches
Young children can be quite active, posing another challenge for keeping patches in place. We recommend using extra tape to secure the patches in place on a child’s back. In addition, a large transparent film dressing (ie, 12×8 in) can be used if quick application is needed. For extra precaution, the use of a tight T-shirt or favorite onesie during the patch test process may be helpful, making it more difficult for little fingers to remove tape edges.

Duration of Patch Testing
Some authors have proposed application of patch tests for 24 hours in pediatric patients, as compared to 48 hours in adults.¹⁰ This recommendation is based on a theory that the reduced application period will decrease the risk for irritant reactions in pediatric patients.

Pediatric Patch Test Screening Series

A summary of the published screening series for patch testing in the pediatric population is provided (Table).

The T.R.U.E. Test (SmartPractice) is approved by the US Food and Drug Administration for use in patients 6 years and older¹¹; however, it may not adequately represent allergen exposures in the pediatric population. Brankov and Jacob¹⁴ found that 10 (40%) of their proposed top 25 pediatric allergens were not detected using the T.R.U.E. Test.

In 2014, the North American Pediatric Patch Test Series was proposed as a basic screening panel for children aged 6 to 12 years.¹² This series of 20 allergens was developed based on a literature review of pediatric patch test results and case reports as well as a database review. The authors proposed additional allergens to be considered based on patient history.¹²

More recently, a 2017 American Contact Dermatitis Society physician work group proposed the Pediatric Baseline Patch Test Series. This series of 38 allergens for children aged 6 to 18 years was developed based on expert consensus.⁸ Studies to determine the efficacy of this series have yet to be conducted, but it may have high sensitivity in detecting relevant allergens in children as demonstrated by a theoretical detection rate of 84%.¹⁴

There are 2 recommended patch test series for allergic diaper dermatitis.¹⁵ The first series focuses on 23 potential allergens found in wet wipes and topical diaper preparations. The second series contains 10 potential allergens found in diapers. These series contain common topical medications for children including corticosteroids, antimicrobials, and sensitizers specific to diapers such as rubbers and adhesives.¹⁵

Similar to adults, it may be difficult to designate one screening panel that can identify all relevant allergens in children; thus, it is always important to obtain a thorough exposure history and customize testing to suspected allergens and/or patient products based on history and clinical relevance.

Unique Pediatric Allergens

Hobbies
Sports gear such as shin guards and splints often contain allergens such as formaldehyde resin, thiuram mix, and dialkyl thioureas.¹⁶ Perioral dermatitis may be caused by musical instrument mouthpieces containing nickel.⁶

Preservatives
Commonly reported causes of ACD in children include methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) found in wet wipes. A 2016 analysis of diaper wipes showed a low prevalence of MI (6.3%) and MCI (1.6%) in these products, which may reflect the industry’s awareness of these potential allergens and a subsequent change in the preservatives they utilize.¹⁷ However, the prevalence of MCI/MI contact allergy may be on the rise due to the popularity of homemade slime, which is made from common household products such as laundry detergent, dishwashing soap, and liquid glue. The Pediatric Baseline Patch Test Series captures most of the potential allergens in these homemade slime recipes and is recommended for use in pediatric patients suspected of having dermatitis secondary to playing with slime.^8,18

Toilet Seat Dermatitis
Toilet seat dermatitis presents as a pruritic dermatitis on the posterior upper thighs and buttocks. Although most cases of toilet seat dermatitis are irritant rather than allergic, potential allergens include plastics, fragrances, and components of cleaning products. Thus, physicians should maintain a high index of suspicion for ACD to toilet seats.¹⁹

Fragrance and Natural Ingredients
A 2018 study evaluating personal care products marketed specifically for infants and children found that 55% of products (294/533) contained at least 1 common allergen, with fragrance being the most common (48% [255/533]). Other common allergens include betaines (18%), propylene glycol (9%), lanolin (6%), and MCI/MI (3%).²⁰ Caregivers should be advised against the myth that natural products are safer and less allergenic and should be provided with resources such as the Contact Allergen Management Program (CAMP) database (https://www.contactderm.org/resources/acds-camp) for safe alternative personal care products.

Metal Allergens
Nickel, the American Contact Dermatitis Society 2008 Allergen of the Year, is another common allergen that affects children. Nickel allergy, commonly thought to affect the ears due to jewelry and ear piercing, may actually be found in a wide range of daily items such as braces, eyeglasses, keys, zippers, school chairs, electronics, toys, and even food.^3,6,21,22 With increased use of electronics in children of all ages, nickel found in mobile phones and other devices may be of particular concern. Caregivers can use a case or cover for metallic-appearing electronics.

Final Interpretation

Pediatric ACD is common. With limited surface area for patch testing in children, we recommend customized panels based on patient history and exposure. It is important for clinicians to recognize the unique causes of ACD in children and develop age-appropriate management plans.

The pediatric population has a unique product exposure profile due to the many care products specifically marketed for use in children. In fact, the prevalence of allergic contact dermatitis (ACD) in children may be as high as 24.5% in the United States.¹ In patch tested children, relevant positive reaction rates of 56.7% and 48% have been reported by the North American Contact Dermatitis Group and the Pediatric Contact Dermatitis Registry, respectively.^2,3 In this article, we provide an overview of current trends in pediatric patch testing as well as specific considerations in this patient population.

Patch Test Reactions in Children

Several publications have documented pediatric patch test reactions. The North American Contact Dermatitis Group reported patch test results in 883 children from the United States and Canada (2005-2012).² The most common reactions were nickel (28.1%), cobalt (12.3%), neomycin (7.1%), balsam of Peru (5.7%), lanolin (5.5%), and fragrance mix I (5.2%). When compared to adults, children were more likely to have relevant positive patch tests to nickel, cobalt, and compositae mix.² In comparison, data from the Pediatric Contact Dermatitis Registry showed that the most common reactions in 1142 children in the United States (2015-2016) were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), and propylene glycol (6.8%).³

Allergen sensitivities may vary based on geographic region. In Spain, children showed the highest sensitivities to thiomersal (10.2%), cobalt (9.1%), colophony (9.1%), paraphenylenediamine (8.3%), mercury (7.9%), potassium dichromate (7.9%), and nickel (6.4%).⁴

Pediatric Patch Testing Pearls

History of Product Use
From diapers to drama club, pediatric exposures and sources of ACD are not the same as those seen in adults. Because obtaining a medical history from a toddler can be exasperating, the patient’s caregivers should be asked about potential exposures, ranging from personal care products and diapers to school activities, hobbies, and sports.^5,6 It is important to keep in mind that the patient’s primary caregiver may not be the only individual who applies products to the child.⁷

Application of Allergens
Children are not merely small adults, but they usually do have smaller backs than adult patients. This reduced surface area means that the patch tester must carefully select the allergens to be patch tested. For reference, the back of a typical 6-year-old child can fit 40 to 60 allergens during patch testing.⁸

Patch Test Chambers
In children, the use of plastic patch test chambers may be preferred over aluminum chambers. Children with persistent pruritic subcutaneous nodules induced by aluminum-based vaccines also may have delayed-type sensitivity reactions to aluminum.⁹ These patients could react to the aluminum present in some patch test chambers, making interpretation of the results difficult. The authors (A.R.A. and M.R.) typically use plastic chambers in the pediatric population.

Managing Expectations
As with other procedures in the pediatric population, patch testing can elicit emotions of fear, anxiety, and distrust. Video distraction and/or role-playing games may help capture the attention of children and can be particularly helpful during patch application. Children may be apprehensive about the term allergy testing if they are familiar with the term needle testing from previous allergies.⁵

Securing Patches
Young children can be quite active, posing another challenge for keeping patches in place. We recommend using extra tape to secure the patches in place on a child’s back. In addition, a large transparent film dressing (ie, 12×8 in) can be used if quick application is needed. For extra precaution, the use of a tight T-shirt or favorite onesie during the patch test process may be helpful, making it more difficult for little fingers to remove tape edges.

Duration of Patch Testing
Some authors have proposed application of patch tests for 24 hours in pediatric patients, as compared to 48 hours in adults.¹⁰ This recommendation is based on a theory that the reduced application period will decrease the risk for irritant reactions in pediatric patients.

Pediatric Patch Test Screening Series

A summary of the published screening series for patch testing in the pediatric population is provided (Table).

The T.R.U.E. Test (SmartPractice) is approved by the US Food and Drug Administration for use in patients 6 years and older¹¹; however, it may not adequately represent allergen exposures in the pediatric population. Brankov and Jacob¹⁴ found that 10 (40%) of their proposed top 25 pediatric allergens were not detected using the T.R.U.E. Test.

In 2014, the North American Pediatric Patch Test Series was proposed as a basic screening panel for children aged 6 to 12 years.¹² This series of 20 allergens was developed based on a literature review of pediatric patch test results and case reports as well as a database review. The authors proposed additional allergens to be considered based on patient history.¹²

More recently, a 2017 American Contact Dermatitis Society physician work group proposed the Pediatric Baseline Patch Test Series. This series of 38 allergens for children aged 6 to 18 years was developed based on expert consensus.⁸ Studies to determine the efficacy of this series have yet to be conducted, but it may have high sensitivity in detecting relevant allergens in children as demonstrated by a theoretical detection rate of 84%.¹⁴

There are 2 recommended patch test series for allergic diaper dermatitis.¹⁵ The first series focuses on 23 potential allergens found in wet wipes and topical diaper preparations. The second series contains 10 potential allergens found in diapers. These series contain common topical medications for children including corticosteroids, antimicrobials, and sensitizers specific to diapers such as rubbers and adhesives.¹⁵

Similar to adults, it may be difficult to designate one screening panel that can identify all relevant allergens in children; thus, it is always important to obtain a thorough exposure history and customize testing to suspected allergens and/or patient products based on history and clinical relevance.

Unique Pediatric Allergens

Hobbies
Sports gear such as shin guards and splints often contain allergens such as formaldehyde resin, thiuram mix, and dialkyl thioureas.¹⁶ Perioral dermatitis may be caused by musical instrument mouthpieces containing nickel.⁶

Preservatives
Commonly reported causes of ACD in children include methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) found in wet wipes. A 2016 analysis of diaper wipes showed a low prevalence of MI (6.3%) and MCI (1.6%) in these products, which may reflect the industry’s awareness of these potential allergens and a subsequent change in the preservatives they utilize.¹⁷ However, the prevalence of MCI/MI contact allergy may be on the rise due to the popularity of homemade slime, which is made from common household products such as laundry detergent, dishwashing soap, and liquid glue. The Pediatric Baseline Patch Test Series captures most of the potential allergens in these homemade slime recipes and is recommended for use in pediatric patients suspected of having dermatitis secondary to playing with slime.^8,18

Toilet Seat Dermatitis
Toilet seat dermatitis presents as a pruritic dermatitis on the posterior upper thighs and buttocks. Although most cases of toilet seat dermatitis are irritant rather than allergic, potential allergens include plastics, fragrances, and components of cleaning products. Thus, physicians should maintain a high index of suspicion for ACD to toilet seats.¹⁹

Fragrance and Natural Ingredients
A 2018 study evaluating personal care products marketed specifically for infants and children found that 55% of products (294/533) contained at least 1 common allergen, with fragrance being the most common (48% [255/533]). Other common allergens include betaines (18%), propylene glycol (9%), lanolin (6%), and MCI/MI (3%).²⁰ Caregivers should be advised against the myth that natural products are safer and less allergenic and should be provided with resources such as the Contact Allergen Management Program (CAMP) database (https://www.contactderm.org/resources/acds-camp) for safe alternative personal care products.

Metal Allergens
Nickel, the American Contact Dermatitis Society 2008 Allergen of the Year, is another common allergen that affects children. Nickel allergy, commonly thought to affect the ears due to jewelry and ear piercing, may actually be found in a wide range of daily items such as braces, eyeglasses, keys, zippers, school chairs, electronics, toys, and even food.^3,6,21,22 With increased use of electronics in children of all ages, nickel found in mobile phones and other devices may be of particular concern. Caregivers can use a case or cover for metallic-appearing electronics.

Final Interpretation

Pediatric ACD is common. With limited surface area for patch testing in children, we recommend customized panels based on patient history and exposure. It is important for clinicians to recognize the unique causes of ACD in children and develop age-appropriate management plans.

The pediatric population has a unique product exposure profile due to the many care products specifically marketed for use in children. In fact, the prevalence of allergic contact dermatitis (ACD) in children may be as high as 24.5% in the United States.¹ In patch tested children, relevant positive reaction rates of 56.7% and 48% have been reported by the North American Contact Dermatitis Group and the Pediatric Contact Dermatitis Registry, respectively.^2,3 In this article, we provide an overview of current trends in pediatric patch testing as well as specific considerations in this patient population.

Patch Test Reactions in Children

Several publications have documented pediatric patch test reactions. The North American Contact Dermatitis Group reported patch test results in 883 children from the United States and Canada (2005-2012).² The most common reactions were nickel (28.1%), cobalt (12.3%), neomycin (7.1%), balsam of Peru (5.7%), lanolin (5.5%), and fragrance mix I (5.2%). When compared to adults, children were more likely to have relevant positive patch tests to nickel, cobalt, and compositae mix.² In comparison, data from the Pediatric Contact Dermatitis Registry showed that the most common reactions in 1142 children in the United States (2015-2016) were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), and propylene glycol (6.8%).³

Allergen sensitivities may vary based on geographic region. In Spain, children showed the highest sensitivities to thiomersal (10.2%), cobalt (9.1%), colophony (9.1%), paraphenylenediamine (8.3%), mercury (7.9%), potassium dichromate (7.9%), and nickel (6.4%).⁴

Pediatric Patch Testing Pearls

History of Product Use
From diapers to drama club, pediatric exposures and sources of ACD are not the same as those seen in adults. Because obtaining a medical history from a toddler can be exasperating, the patient’s caregivers should be asked about potential exposures, ranging from personal care products and diapers to school activities, hobbies, and sports.^5,6 It is important to keep in mind that the patient’s primary caregiver may not be the only individual who applies products to the child.⁷

Application of Allergens
Children are not merely small adults, but they usually do have smaller backs than adult patients. This reduced surface area means that the patch tester must carefully select the allergens to be patch tested. For reference, the back of a typical 6-year-old child can fit 40 to 60 allergens during patch testing.⁸

Patch Test Chambers
In children, the use of plastic patch test chambers may be preferred over aluminum chambers. Children with persistent pruritic subcutaneous nodules induced by aluminum-based vaccines also may have delayed-type sensitivity reactions to aluminum.⁹ These patients could react to the aluminum present in some patch test chambers, making interpretation of the results difficult. The authors (A.R.A. and M.R.) typically use plastic chambers in the pediatric population.

Managing Expectations
As with other procedures in the pediatric population, patch testing can elicit emotions of fear, anxiety, and distrust. Video distraction and/or role-playing games may help capture the attention of children and can be particularly helpful during patch application. Children may be apprehensive about the term allergy testing if they are familiar with the term needle testing from previous allergies.⁵

Securing Patches
Young children can be quite active, posing another challenge for keeping patches in place. We recommend using extra tape to secure the patches in place on a child’s back. In addition, a large transparent film dressing (ie, 12×8 in) can be used if quick application is needed. For extra precaution, the use of a tight T-shirt or favorite onesie during the patch test process may be helpful, making it more difficult for little fingers to remove tape edges.

Duration of Patch Testing
Some authors have proposed application of patch tests for 24 hours in pediatric patients, as compared to 48 hours in adults.¹⁰ This recommendation is based on a theory that the reduced application period will decrease the risk for irritant reactions in pediatric patients.

Pediatric Patch Test Screening Series

A summary of the published screening series for patch testing in the pediatric population is provided (Table).

The T.R.U.E. Test (SmartPractice) is approved by the US Food and Drug Administration for use in patients 6 years and older¹¹; however, it may not adequately represent allergen exposures in the pediatric population. Brankov and Jacob¹⁴ found that 10 (40%) of their proposed top 25 pediatric allergens were not detected using the T.R.U.E. Test.

In 2014, the North American Pediatric Patch Test Series was proposed as a basic screening panel for children aged 6 to 12 years.¹² This series of 20 allergens was developed based on a literature review of pediatric patch test results and case reports as well as a database review. The authors proposed additional allergens to be considered based on patient history.¹²

More recently, a 2017 American Contact Dermatitis Society physician work group proposed the Pediatric Baseline Patch Test Series. This series of 38 allergens for children aged 6 to 18 years was developed based on expert consensus.⁸ Studies to determine the efficacy of this series have yet to be conducted, but it may have high sensitivity in detecting relevant allergens in children as demonstrated by a theoretical detection rate of 84%.¹⁴

There are 2 recommended patch test series for allergic diaper dermatitis.¹⁵ The first series focuses on 23 potential allergens found in wet wipes and topical diaper preparations. The second series contains 10 potential allergens found in diapers. These series contain common topical medications for children including corticosteroids, antimicrobials, and sensitizers specific to diapers such as rubbers and adhesives.¹⁵

Similar to adults, it may be difficult to designate one screening panel that can identify all relevant allergens in children; thus, it is always important to obtain a thorough exposure history and customize testing to suspected allergens and/or patient products based on history and clinical relevance.

Unique Pediatric Allergens

Hobbies
Sports gear such as shin guards and splints often contain allergens such as formaldehyde resin, thiuram mix, and dialkyl thioureas.¹⁶ Perioral dermatitis may be caused by musical instrument mouthpieces containing nickel.⁶

Preservatives
Commonly reported causes of ACD in children include methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) found in wet wipes. A 2016 analysis of diaper wipes showed a low prevalence of MI (6.3%) and MCI (1.6%) in these products, which may reflect the industry’s awareness of these potential allergens and a subsequent change in the preservatives they utilize.¹⁷ However, the prevalence of MCI/MI contact allergy may be on the rise due to the popularity of homemade slime, which is made from common household products such as laundry detergent, dishwashing soap, and liquid glue. The Pediatric Baseline Patch Test Series captures most of the potential allergens in these homemade slime recipes and is recommended for use in pediatric patients suspected of having dermatitis secondary to playing with slime.^8,18

Toilet Seat Dermatitis
Toilet seat dermatitis presents as a pruritic dermatitis on the posterior upper thighs and buttocks. Although most cases of toilet seat dermatitis are irritant rather than allergic, potential allergens include plastics, fragrances, and components of cleaning products. Thus, physicians should maintain a high index of suspicion for ACD to toilet seats.¹⁹

Fragrance and Natural Ingredients
A 2018 study evaluating personal care products marketed specifically for infants and children found that 55% of products (294/533) contained at least 1 common allergen, with fragrance being the most common (48% [255/533]). Other common allergens include betaines (18%), propylene glycol (9%), lanolin (6%), and MCI/MI (3%).²⁰ Caregivers should be advised against the myth that natural products are safer and less allergenic and should be provided with resources such as the Contact Allergen Management Program (CAMP) database (https://www.contactderm.org/resources/acds-camp) for safe alternative personal care products.

Metal Allergens
Nickel, the American Contact Dermatitis Society 2008 Allergen of the Year, is another common allergen that affects children. Nickel allergy, commonly thought to affect the ears due to jewelry and ear piercing, may actually be found in a wide range of daily items such as braces, eyeglasses, keys, zippers, school chairs, electronics, toys, and even food.^3,6,21,22 With increased use of electronics in children of all ages, nickel found in mobile phones and other devices may be of particular concern. Caregivers can use a case or cover for metallic-appearing electronics.

Final Interpretation

Pediatric ACD is common. With limited surface area for patch testing in children, we recommend customized panels based on patient history and exposure. It is important for clinicians to recognize the unique causes of ACD in children and develop age-appropriate management plans.

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure). 

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure). 

The Diagnosis: Irritant Contact Dermatitis and Hyperpigmentation Due to Juglone  

Clinical suspicion, resemblance to similar cases, and questioning the patient about his behavior prior to the onset of symptoms led to the diagnosis of irritant contact dermatitis and hyperpigmentation due to juglone in this case. Walnuts belong to the botanical family of Juglandaceae and are the seed of the trees of the genus Juglans, which encompass 24 different species. The nuts from all species included in this genus are edible.¹ The most well-known species of walnut is the common walnut (Juglans regia), which is native to the Balkans region in southeast Europe, southwest and central Asia extending to the Himalayas, and southwest China.¹  

Walnut fruits are rich in phenolic compounds. Thirteen phenolic compounds have been identified in walnut husks including chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, gallic acid, ellagic acid, protocatechuic acid, syringic acid, vanillic acid, catechin, epicatechin, myricetin, and juglone.² Juglone, also called 5-hydroxy-1,4-napthoquinone, is a yellow naphthoquinone pigment that occurs naturally in the leaves, roots, husks, and bark of plants in the Juglandaceae family, particularly the black walnut (Juglans nigra).^3,4 

Juglans regia, also known as English or Persian walnut, contains potent chemical constituents and has been used to treat diverse ailments such as diarrhea, hyperglycemia, cancer, infectious diseases, anorexia, asthma, helminthiasis, arthritis, sinusitis, stomachache, and skin disorders (eg, eczema; acne; alopecia; scalp itching, peeling, and dandruff), and as an adjunctive emollient and itch-relieving treatment.^5,6 

The juice of walnut shells from the J regia tree have been used for centuries to color the skin and hair.⁷ Irritation and skin hyperpigmentation have been associated with topical walnut use.⁵ As a naphthoquinone, juglone also is reported to exert some toxic effects on normal tissues including acute irritant contact dermatitis.⁴ As the active ingredient from the green husk of walnuts, it has been considered a strong sensitizer in guinea pigs,¹ but contact sensitivity in humans rarely has been reported.⁷  

Juglone is known to react with the keratin proteins present in the skin to form sclerojuglonic compounds, which have UV protection properties and a red-brown color.⁸ The resulting reaction gives rise to chromophore groups with a strong pigmenting action that absorbs visible colors (especially violet) and reflects yellow and red, resulting in the coloration ranging from red to deep brown.⁷ The mechanism of skin pigmentation does not involve the melanocytes. Hyperchromia involving the hands--particularly the palms, fingers, and nails--lasts 1 to 4 weeks depending on the intensity of the pigmentation. Housewives and agricultural workers are the at-risk population.⁷ Acute irritant contact dermatitis and hyperpigmentation due to juglone mainly has been observed during the early autumn in agricultural workers and housewives who remove the green husk of walnuts.⁹  

Addison disease can present with pigmentary changes in the skin and mucous membranes; it also is accompanied by fatigue, anorexia, weakness, and weight loss, none of which were noted in our patient. A fixed drug eruption tends to have an annular or oval form and is related to the intake of medication (mostly antibiotics) up to 2 weeks prior to the onset of the dermatosis. Our patient did not have any chronic disease or take any medication prior to the dermatosis and lacked the classic clinical morphology of this entity. Hemochromatosis affects not only the skin but also the liver, myocardial fibers, and other internal organs. Our patient did not have any clinical manifestations of liver or heart failure or diabetes mellitus.  

Our patient was treated with drainage of the blisters. Due to the extent of the dermatosis, prednisone 25 mg/d also was initiated. The patient was instructed to avoid direct contact with the husk of walnuts. At 1-month follow-up, the hyperpigmentation had resolved with no relapse (Figure). 

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

The Diagnosis: Irritant Contact Dermatitis  

A slang term for volatile alkyl nitrites, poppers are inhaled for recreational purposes. They produce    rapid-onset euphoria and sexual arousal, as well as relax anal and vaginal sphincters, facilitating sexual intercourse. Alkyl nitrites initially were developed to treat coronary disease and angina but were replaced by more potent drugs.¹ Because of their psychoactive effects and smooth muscle relaxation properties, they are widely used by homosexual and bisexual men.^1-3 The term poppers was originated by the sound generated when the glass vials are crushed; currently, they also may be found in other formats.¹  

Nausea, hypotension, and headache are mild common adverse effects of volatile alkyl nitrites¹; cardiac arrhythmia, oxidative hemolysis,⁴ and poppers maculopathy^5,6 with permanent eye damage also have been reported.⁷ On the skin, volatile alkyl nitrites induce irritant contact dermatitis that heals without scarring, characteristically involving the face and upper thoracic region, as they are volatile vapors.² However, the reaction can occur elsewhere. There have been reports of contact dermatitis on other locations, such as the thigh or the ankle, due to vials broken while stored in pockets or on the cuff of the socks.¹ There also is a report of irritant contact dermatitis manifesting as a penile ulcer.³ Albeit rare, allergic contact dermatitis to volatile alkyl nitrites and other nitrites also can occur.⁸  

The abuse of alkyl nitrites may increase the risk for sexually transmitted infections (STIs), as they may decrease safer sexual practices and increase the propensity to engage in risky sexual behavior. It has been suggested to screen for STIs in patients with history of volatile alkyl nitrite use. In the past, volatile alkyl nitrites were believed to be a potential vector of human immunodeficiency virus.⁹ Other popular drugs used in social context or "club drugs," such as 3,4-methylenedioxymethamphetamine, gamma hydroxybutyrate, methamphetamine, and ketamine, do not produce irritant dermatitis as an adverse cutaneous reaction.¹⁰ The differential diagnosis in our patient included herpes simplex virus and contagious impetigo¹ as well as bullous lupus erythematosus and periorificial dermatitis; however, the clinical picture, acute onset of the reaction, and the patient's medical history were critical in making the correct diagnosis.  

The patient was treated with topical hydrocortisone and fusidic acid cream twice daily for 7 days with complete response. Sexually transmitted infection screening was unremarkable. We suggest performing an STI workup on patients with history of volatile alkyl nitrite use. 

Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

It has been 40 years since the first reported case of IgE-mediated natural rubber latex allergy, which was soon followed by a global epidemic of allergic and anaphylactic reactions.^1,2 Resolution came through insightful work in the 1990s that led to the removal of cornstarch powder and a switch to nonpowdered latex and synthetic examination gloves.² Also discovered during this period was the cross-reactivity of many patients to latex and various fruits. This column will briefly discuss the latex/fruit allergy syndrome, which should be considered in patients who are sensitive to various skincare products.

tookapic/Pixabay

Research substantiates reports

Blanco et al. conducted a prospective study in their outpatient clinic in 25 patients diagnosed with latex allergy, published in 1994.They used a clinical questionnaire, skin-prick tests, skin test with a latex extract, and identification of total and specific IgE to help ascertain clinical characteristics and cross-reactivity. Of the 23 women and 2 men in the study (mean age 33, plus or minus 9 years), 9 (36%) experienced latex-induced reactions characterized by systemic anaphylaxis. In 13 patients (52%), 42 food allergies were identified, and 23 included systemic anaphylaxis. Avocado (9), chestnut (9), banana (7), kiwi (5), and papaya (3) were the most common foods to cause hypersensitivities. The researchers concluded that their small study supported the reality of a “latex-fruit syndrome.”³

Another study aimed to characterize the cross-reactivity of latex and foods and evaluate clinical significance. Beezhold et al. examined 47 patients allergic to latex and 46 nonallergic controls. The investigators found immunologic reactivity to foods to be prevalent (33 latex-allergic patients and seven controls), with 27% of food skin-prick tests positive in the latex-allergic group. In addition, clinical symptoms were linked to 27% of positive skin-prick tests. Among the 17 patients who displayed clinical allergies to at least one food, 14 showed local sensitivity reactions, with anaphylaxis noted in 11. Avocado (53%), potato (40%), banana (38%), tomato (28%), chestnut (28%), and kiwi (17%) were the foods most frequently cited for provoking a skin test reaction. The authors observed extensive cross-reactivity between latex sensitivity and particular foods, with potatoes and tomatoes reported for the first time.⁴

In 1997, Brehler et al. studied serum samples from 136 patients whose immediate hypersensitivity to latex proteins was clinically observable and documented. The samples were assessed for IgE antibodies against several fruits, with fruit-specific IgE antibodies recorded in 69.1%. Radioallergosorbent (RAST) -inhibition tests yielded the recognition of cross-reacting IgE antibodies in latex and multiple fruit allergens: avocado, banana, chestnut, fig, kiwi, mango, melon, papaya, passion fruit, peach, pineapple, and tomato. The investigators recorded 112 intolerance reactions and noted that 42.5% of their patients reported allergic symptoms after consuming these fruits. Fruit-specific IgE antibodies were detected in only 32.1% of these patients, suggesting to the researchers that serologic tests were suboptimal in forecasting food hypersensitivities in patients who are allergic to latex.⁵

Cross-reactivity with banana

Mäkinen-Kiljunen studied 47 patients to investigate banana allergy in patients with latex allergy in 1994, measuring latex-, banana-, and pollen-specific (birch, timothy, and mugwort) IgE. Thirty-one patients were also given skin-prick tests with banana and were queried about reactions after consuming bananas. Of the 47 sera samples, latex RAST results were positive in 31 and banana RAST results in 26. RAST results from latex and banana were correlated (25 of the 31 latex RAST-positive samples were also banana RAST-positive), but not with pollen. Sixteen of the 31 patients who ate banana reported symptoms, and 11 of the 31 patients given the banana skin-prick test showed positive results. The author confirmed the cross-reactivity of IgE antibodies for latex and banana, identifying for the first time a structurally similar antigen/allergen as at least one antigen from banana fused with an antigen from latex in crossed-line immunoelectrophoresis.⁶

In 1998, Mikkola et al. investigated whether proteins similar to hevein, a major natural rubber latex allergen, are present in banana and account for cross-reactivity between these botanicals. Immunoblotting revealed that 9 of 15 sera from latex-allergic patients with IgE to hevein also bound to 32- and 33-kd banana proteins. Studies using ELISA [enzyme-linked immunosorbent assay] showed that the common presentation of hypersensitivity to banana among patients allergic to latex could be attributed to cross-reacting IgE antibodies binding to epitopes in hevein and in the then-newly identified hevein-like endochitinase found in banana.⁷

Cross-reactivity with avocado

In response to reports of an association between allergy to natural rubber latex and avocado, Ahlroth et al. investigated cross-reactive proteins between natural rubber latex and avocado in 1995 by using skin-prick tests with fresh avocado on 11 patients and the sera of 18 patients with known latex allergy for IgE antibodies. Fourteen of the 18 sera were found to have IgE antibodies binding to 17 distinct avocado proteins, with multiple immunoblot experiments and skin-prick test results (positive in 7 of 11 patients) revealing marked immunologic cross-reactivity between latex and avocado.⁸

In 1998, Chen et al. set out to identify the cross-sensitizing allergen between latex and avocado, with hevein suspected. The researchers looked at sera samples from 118 health care workers allergic to latex and 78 patients with spina bifida who were allergic to latex. They noted a robust correlation between the prevalence of seropositive IgE antibodies to avocado in the presence of hevein-specific IgE antibodies in both groups. All members in the spina bifida group and 91 (73%) of the health care workers had positive IgE antibodies to hevein and high IgE values to avocado. Additional results supported the conclusion that sensitization to avocado in the majority of people allergic to latex is engendered by IgE-binding epitopes found in hevein.⁹

A year later, Diaz-Perales et al. considered the potential relevance of chitinases and complex glycans as factors in the then newly described latex/food syndrome, particularly in avocado, banana, and chestnuts. The investigators culled extracts from 20 various plant foods as well as latex. In immunoblot inhibition assays, the primary allergen and class I chitinase in avocado, Prs a 1, and the latex extract potently or completely blocked IgE binding by these constituents. Polyclonal antibodies to chitinases and sera from patients with latex/fruit allergy responded to reactive proteins of about 30-45 kd (putative class I chitinases) in chestnut, cherimoya, kiwi, mango, papaya, passion fruit, tomato, and wheat flour extracts. The glycans complex was deemed to be irrelevant in latex/fruit cross-reactivity, but the researchers found the putative class I chitinases to be notable players in the latex/fruit syndrome.¹⁰

According to Wagner and Breitender, anywhere from 30%-50% of people with known latex allergy also evince a related hypersensitivity or allergy to various plant-derived foods, with avocado, banana, chestnut, kiwi, peach, tomato, potato, and bell pepper among the foods most frequently linked to latex/fruit syndrome. They summarize that several plant defense proteins have been shown to be involved in the syndrome, with the most prominent, class I chitinases with an N-terminal hevein-like domain, having been found to cross-react with hevein (Hev b 6.02), a major IgE-binding allergen for individuals allergic to latex. A beta-1,3-glucanase, a key latex allergen, has also shown cross-reactivity with proteins of bell pepper, and another significant latex allergen, Hev b 7, a patatin-like protein, cross-reacts with its analogous protein in potato.¹¹

Conclusion

It is unknown whether latex allergy precedes or follows food allergy.11 The latex/food syndrome itself merits attention as a significant source of hypersensitivity to natural cosmeceutical ingredients. Dermatologists should be aware of the lengthy list of cross-reacting plant-derived products, particularly when it comes to reviewing topical product ingredients with susceptible or allergic patients. Latex-allergic patients may react to these natural ingredients in food or when topically applied to the skin.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nutter AF. Br J Dermatol 1979 Nov;101(5):597-8.

2. Kelly KJ et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1212-16.

3. Blanco C et al. Ann Allergy. 1994 Oct;73(4):309-14.

4. Beezhold DH et al. Clin Exp Allergy. 1996 Apr;26(4):416-22.

5. Brehler R et al. Allergy. 1997 Apr;52(4):404-10.

6. Mäkinen-Kiljunen S. J Allergy Clin Immunol. 1994 Jun;93(6):990-6.

7. Mikkola JH et al. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):1005-12.

8. Ahlroth M et al. J Allergy Clin Immunol. 1995 Aug;96(2):167-73.

9. Chen Z et al. J Allergy Clin Immunol. 1998 Sep;102(3):476-81.

10. Diaz-Perales A et al. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):681-7.

11. Wagner S et al. Biochem Soc Trans. 2002 Nov;30(Pt 6):935-40.

It has been 40 years since the first reported case of IgE-mediated natural rubber latex allergy, which was soon followed by a global epidemic of allergic and anaphylactic reactions.^1,2 Resolution came through insightful work in the 1990s that led to the removal of cornstarch powder and a switch to nonpowdered latex and synthetic examination gloves.² Also discovered during this period was the cross-reactivity of many patients to latex and various fruits. This column will briefly discuss the latex/fruit allergy syndrome, which should be considered in patients who are sensitive to various skincare products.

tookapic/Pixabay

Research substantiates reports

Blanco et al. conducted a prospective study in their outpatient clinic in 25 patients diagnosed with latex allergy, published in 1994.They used a clinical questionnaire, skin-prick tests, skin test with a latex extract, and identification of total and specific IgE to help ascertain clinical characteristics and cross-reactivity. Of the 23 women and 2 men in the study (mean age 33, plus or minus 9 years), 9 (36%) experienced latex-induced reactions characterized by systemic anaphylaxis. In 13 patients (52%), 42 food allergies were identified, and 23 included systemic anaphylaxis. Avocado (9), chestnut (9), banana (7), kiwi (5), and papaya (3) were the most common foods to cause hypersensitivities. The researchers concluded that their small study supported the reality of a “latex-fruit syndrome.”³

Another study aimed to characterize the cross-reactivity of latex and foods and evaluate clinical significance. Beezhold et al. examined 47 patients allergic to latex and 46 nonallergic controls. The investigators found immunologic reactivity to foods to be prevalent (33 latex-allergic patients and seven controls), with 27% of food skin-prick tests positive in the latex-allergic group. In addition, clinical symptoms were linked to 27% of positive skin-prick tests. Among the 17 patients who displayed clinical allergies to at least one food, 14 showed local sensitivity reactions, with anaphylaxis noted in 11. Avocado (53%), potato (40%), banana (38%), tomato (28%), chestnut (28%), and kiwi (17%) were the foods most frequently cited for provoking a skin test reaction. The authors observed extensive cross-reactivity between latex sensitivity and particular foods, with potatoes and tomatoes reported for the first time.⁴

In 1997, Brehler et al. studied serum samples from 136 patients whose immediate hypersensitivity to latex proteins was clinically observable and documented. The samples were assessed for IgE antibodies against several fruits, with fruit-specific IgE antibodies recorded in 69.1%. Radioallergosorbent (RAST) -inhibition tests yielded the recognition of cross-reacting IgE antibodies in latex and multiple fruit allergens: avocado, banana, chestnut, fig, kiwi, mango, melon, papaya, passion fruit, peach, pineapple, and tomato. The investigators recorded 112 intolerance reactions and noted that 42.5% of their patients reported allergic symptoms after consuming these fruits. Fruit-specific IgE antibodies were detected in only 32.1% of these patients, suggesting to the researchers that serologic tests were suboptimal in forecasting food hypersensitivities in patients who are allergic to latex.⁵

Cross-reactivity with banana

Mäkinen-Kiljunen studied 47 patients to investigate banana allergy in patients with latex allergy in 1994, measuring latex-, banana-, and pollen-specific (birch, timothy, and mugwort) IgE. Thirty-one patients were also given skin-prick tests with banana and were queried about reactions after consuming bananas. Of the 47 sera samples, latex RAST results were positive in 31 and banana RAST results in 26. RAST results from latex and banana were correlated (25 of the 31 latex RAST-positive samples were also banana RAST-positive), but not with pollen. Sixteen of the 31 patients who ate banana reported symptoms, and 11 of the 31 patients given the banana skin-prick test showed positive results. The author confirmed the cross-reactivity of IgE antibodies for latex and banana, identifying for the first time a structurally similar antigen/allergen as at least one antigen from banana fused with an antigen from latex in crossed-line immunoelectrophoresis.⁶

In 1998, Mikkola et al. investigated whether proteins similar to hevein, a major natural rubber latex allergen, are present in banana and account for cross-reactivity between these botanicals. Immunoblotting revealed that 9 of 15 sera from latex-allergic patients with IgE to hevein also bound to 32- and 33-kd banana proteins. Studies using ELISA [enzyme-linked immunosorbent assay] showed that the common presentation of hypersensitivity to banana among patients allergic to latex could be attributed to cross-reacting IgE antibodies binding to epitopes in hevein and in the then-newly identified hevein-like endochitinase found in banana.⁷

Cross-reactivity with avocado

In response to reports of an association between allergy to natural rubber latex and avocado, Ahlroth et al. investigated cross-reactive proteins between natural rubber latex and avocado in 1995 by using skin-prick tests with fresh avocado on 11 patients and the sera of 18 patients with known latex allergy for IgE antibodies. Fourteen of the 18 sera were found to have IgE antibodies binding to 17 distinct avocado proteins, with multiple immunoblot experiments and skin-prick test results (positive in 7 of 11 patients) revealing marked immunologic cross-reactivity between latex and avocado.⁸

In 1998, Chen et al. set out to identify the cross-sensitizing allergen between latex and avocado, with hevein suspected. The researchers looked at sera samples from 118 health care workers allergic to latex and 78 patients with spina bifida who were allergic to latex. They noted a robust correlation between the prevalence of seropositive IgE antibodies to avocado in the presence of hevein-specific IgE antibodies in both groups. All members in the spina bifida group and 91 (73%) of the health care workers had positive IgE antibodies to hevein and high IgE values to avocado. Additional results supported the conclusion that sensitization to avocado in the majority of people allergic to latex is engendered by IgE-binding epitopes found in hevein.⁹

A year later, Diaz-Perales et al. considered the potential relevance of chitinases and complex glycans as factors in the then newly described latex/food syndrome, particularly in avocado, banana, and chestnuts. The investigators culled extracts from 20 various plant foods as well as latex. In immunoblot inhibition assays, the primary allergen and class I chitinase in avocado, Prs a 1, and the latex extract potently or completely blocked IgE binding by these constituents. Polyclonal antibodies to chitinases and sera from patients with latex/fruit allergy responded to reactive proteins of about 30-45 kd (putative class I chitinases) in chestnut, cherimoya, kiwi, mango, papaya, passion fruit, tomato, and wheat flour extracts. The glycans complex was deemed to be irrelevant in latex/fruit cross-reactivity, but the researchers found the putative class I chitinases to be notable players in the latex/fruit syndrome.¹⁰

According to Wagner and Breitender, anywhere from 30%-50% of people with known latex allergy also evince a related hypersensitivity or allergy to various plant-derived foods, with avocado, banana, chestnut, kiwi, peach, tomato, potato, and bell pepper among the foods most frequently linked to latex/fruit syndrome. They summarize that several plant defense proteins have been shown to be involved in the syndrome, with the most prominent, class I chitinases with an N-terminal hevein-like domain, having been found to cross-react with hevein (Hev b 6.02), a major IgE-binding allergen for individuals allergic to latex. A beta-1,3-glucanase, a key latex allergen, has also shown cross-reactivity with proteins of bell pepper, and another significant latex allergen, Hev b 7, a patatin-like protein, cross-reacts with its analogous protein in potato.¹¹

Conclusion

It is unknown whether latex allergy precedes or follows food allergy.11 The latex/food syndrome itself merits attention as a significant source of hypersensitivity to natural cosmeceutical ingredients. Dermatologists should be aware of the lengthy list of cross-reacting plant-derived products, particularly when it comes to reviewing topical product ingredients with susceptible or allergic patients. Latex-allergic patients may react to these natural ingredients in food or when topically applied to the skin.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nutter AF. Br J Dermatol 1979 Nov;101(5):597-8.

2. Kelly KJ et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1212-16.

3. Blanco C et al. Ann Allergy. 1994 Oct;73(4):309-14.

4. Beezhold DH et al. Clin Exp Allergy. 1996 Apr;26(4):416-22.

5. Brehler R et al. Allergy. 1997 Apr;52(4):404-10.

6. Mäkinen-Kiljunen S. J Allergy Clin Immunol. 1994 Jun;93(6):990-6.

7. Mikkola JH et al. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):1005-12.

8. Ahlroth M et al. J Allergy Clin Immunol. 1995 Aug;96(2):167-73.

9. Chen Z et al. J Allergy Clin Immunol. 1998 Sep;102(3):476-81.

10. Diaz-Perales A et al. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):681-7.

11. Wagner S et al. Biochem Soc Trans. 2002 Nov;30(Pt 6):935-40.

It has been 40 years since the first reported case of IgE-mediated natural rubber latex allergy, which was soon followed by a global epidemic of allergic and anaphylactic reactions.^1,2 Resolution came through insightful work in the 1990s that led to the removal of cornstarch powder and a switch to nonpowdered latex and synthetic examination gloves.² Also discovered during this period was the cross-reactivity of many patients to latex and various fruits. This column will briefly discuss the latex/fruit allergy syndrome, which should be considered in patients who are sensitive to various skincare products.

tookapic/Pixabay

Research substantiates reports

Blanco et al. conducted a prospective study in their outpatient clinic in 25 patients diagnosed with latex allergy, published in 1994.They used a clinical questionnaire, skin-prick tests, skin test with a latex extract, and identification of total and specific IgE to help ascertain clinical characteristics and cross-reactivity. Of the 23 women and 2 men in the study (mean age 33, plus or minus 9 years), 9 (36%) experienced latex-induced reactions characterized by systemic anaphylaxis. In 13 patients (52%), 42 food allergies were identified, and 23 included systemic anaphylaxis. Avocado (9), chestnut (9), banana (7), kiwi (5), and papaya (3) were the most common foods to cause hypersensitivities. The researchers concluded that their small study supported the reality of a “latex-fruit syndrome.”³

Another study aimed to characterize the cross-reactivity of latex and foods and evaluate clinical significance. Beezhold et al. examined 47 patients allergic to latex and 46 nonallergic controls. The investigators found immunologic reactivity to foods to be prevalent (33 latex-allergic patients and seven controls), with 27% of food skin-prick tests positive in the latex-allergic group. In addition, clinical symptoms were linked to 27% of positive skin-prick tests. Among the 17 patients who displayed clinical allergies to at least one food, 14 showed local sensitivity reactions, with anaphylaxis noted in 11. Avocado (53%), potato (40%), banana (38%), tomato (28%), chestnut (28%), and kiwi (17%) were the foods most frequently cited for provoking a skin test reaction. The authors observed extensive cross-reactivity between latex sensitivity and particular foods, with potatoes and tomatoes reported for the first time.⁴

In 1997, Brehler et al. studied serum samples from 136 patients whose immediate hypersensitivity to latex proteins was clinically observable and documented. The samples were assessed for IgE antibodies against several fruits, with fruit-specific IgE antibodies recorded in 69.1%. Radioallergosorbent (RAST) -inhibition tests yielded the recognition of cross-reacting IgE antibodies in latex and multiple fruit allergens: avocado, banana, chestnut, fig, kiwi, mango, melon, papaya, passion fruit, peach, pineapple, and tomato. The investigators recorded 112 intolerance reactions and noted that 42.5% of their patients reported allergic symptoms after consuming these fruits. Fruit-specific IgE antibodies were detected in only 32.1% of these patients, suggesting to the researchers that serologic tests were suboptimal in forecasting food hypersensitivities in patients who are allergic to latex.⁵

Cross-reactivity with banana

Mäkinen-Kiljunen studied 47 patients to investigate banana allergy in patients with latex allergy in 1994, measuring latex-, banana-, and pollen-specific (birch, timothy, and mugwort) IgE. Thirty-one patients were also given skin-prick tests with banana and were queried about reactions after consuming bananas. Of the 47 sera samples, latex RAST results were positive in 31 and banana RAST results in 26. RAST results from latex and banana were correlated (25 of the 31 latex RAST-positive samples were also banana RAST-positive), but not with pollen. Sixteen of the 31 patients who ate banana reported symptoms, and 11 of the 31 patients given the banana skin-prick test showed positive results. The author confirmed the cross-reactivity of IgE antibodies for latex and banana, identifying for the first time a structurally similar antigen/allergen as at least one antigen from banana fused with an antigen from latex in crossed-line immunoelectrophoresis.⁶

In 1998, Mikkola et al. investigated whether proteins similar to hevein, a major natural rubber latex allergen, are present in banana and account for cross-reactivity between these botanicals. Immunoblotting revealed that 9 of 15 sera from latex-allergic patients with IgE to hevein also bound to 32- and 33-kd banana proteins. Studies using ELISA [enzyme-linked immunosorbent assay] showed that the common presentation of hypersensitivity to banana among patients allergic to latex could be attributed to cross-reacting IgE antibodies binding to epitopes in hevein and in the then-newly identified hevein-like endochitinase found in banana.⁷

Cross-reactivity with avocado

In response to reports of an association between allergy to natural rubber latex and avocado, Ahlroth et al. investigated cross-reactive proteins between natural rubber latex and avocado in 1995 by using skin-prick tests with fresh avocado on 11 patients and the sera of 18 patients with known latex allergy for IgE antibodies. Fourteen of the 18 sera were found to have IgE antibodies binding to 17 distinct avocado proteins, with multiple immunoblot experiments and skin-prick test results (positive in 7 of 11 patients) revealing marked immunologic cross-reactivity between latex and avocado.⁸

In 1998, Chen et al. set out to identify the cross-sensitizing allergen between latex and avocado, with hevein suspected. The researchers looked at sera samples from 118 health care workers allergic to latex and 78 patients with spina bifida who were allergic to latex. They noted a robust correlation between the prevalence of seropositive IgE antibodies to avocado in the presence of hevein-specific IgE antibodies in both groups. All members in the spina bifida group and 91 (73%) of the health care workers had positive IgE antibodies to hevein and high IgE values to avocado. Additional results supported the conclusion that sensitization to avocado in the majority of people allergic to latex is engendered by IgE-binding epitopes found in hevein.⁹

A year later, Diaz-Perales et al. considered the potential relevance of chitinases and complex glycans as factors in the then newly described latex/food syndrome, particularly in avocado, banana, and chestnuts. The investigators culled extracts from 20 various plant foods as well as latex. In immunoblot inhibition assays, the primary allergen and class I chitinase in avocado, Prs a 1, and the latex extract potently or completely blocked IgE binding by these constituents. Polyclonal antibodies to chitinases and sera from patients with latex/fruit allergy responded to reactive proteins of about 30-45 kd (putative class I chitinases) in chestnut, cherimoya, kiwi, mango, papaya, passion fruit, tomato, and wheat flour extracts. The glycans complex was deemed to be irrelevant in latex/fruit cross-reactivity, but the researchers found the putative class I chitinases to be notable players in the latex/fruit syndrome.¹⁰

According to Wagner and Breitender, anywhere from 30%-50% of people with known latex allergy also evince a related hypersensitivity or allergy to various plant-derived foods, with avocado, banana, chestnut, kiwi, peach, tomato, potato, and bell pepper among the foods most frequently linked to latex/fruit syndrome. They summarize that several plant defense proteins have been shown to be involved in the syndrome, with the most prominent, class I chitinases with an N-terminal hevein-like domain, having been found to cross-react with hevein (Hev b 6.02), a major IgE-binding allergen for individuals allergic to latex. A beta-1,3-glucanase, a key latex allergen, has also shown cross-reactivity with proteins of bell pepper, and another significant latex allergen, Hev b 7, a patatin-like protein, cross-reacts with its analogous protein in potato.¹¹

Conclusion

It is unknown whether latex allergy precedes or follows food allergy.11 The latex/food syndrome itself merits attention as a significant source of hypersensitivity to natural cosmeceutical ingredients. Dermatologists should be aware of the lengthy list of cross-reacting plant-derived products, particularly when it comes to reviewing topical product ingredients with susceptible or allergic patients. Latex-allergic patients may react to these natural ingredients in food or when topically applied to the skin.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at [email protected].

References

1. Nutter AF. Br J Dermatol 1979 Nov;101(5):597-8.

2. Kelly KJ et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1212-16.

3. Blanco C et al. Ann Allergy. 1994 Oct;73(4):309-14.

4. Beezhold DH et al. Clin Exp Allergy. 1996 Apr;26(4):416-22.

5. Brehler R et al. Allergy. 1997 Apr;52(4):404-10.

6. Mäkinen-Kiljunen S. J Allergy Clin Immunol. 1994 Jun;93(6):990-6.

7. Mikkola JH et al. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):1005-12.

8. Ahlroth M et al. J Allergy Clin Immunol. 1995 Aug;96(2):167-73.

9. Chen Z et al. J Allergy Clin Immunol. 1998 Sep;102(3):476-81.

10. Diaz-Perales A et al. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):681-7.

11. Wagner S et al. Biochem Soc Trans. 2002 Nov;30(Pt 6):935-40.

Unless you have been living under a rock, you probably already know that the preservative methylisothiazolinone (MI) has caused an epidemic of allergic contact dermatitis (ACD) and was named the 2013 American Contact Dermatitis Society Allergen of the Year.¹ Methylisothiazolinone is not new on the market, but its solo use as a preservative is relatively new. In this article, we review the emergence of MI as a common allergen, discuss North American MI patch test results, and describe common and uncommon sources of MI exposure. We also explore the related isothiazolinones, benzisothiazolinone (BIT) and octylisothiazolinone (OIT).

Background

Methylchloroisothiazolinone (MCI) and MI have been utilized as a preservative in a 3:1 ratio since the 1980s. In 2005, MI was first used alone as a preservative in personal care products in concentrations of up to 100 ppm, which represented a 25-fold increase in exposure to MI in personal care products and thus unleashed an epidemic of ACD.¹ In the 2015 to 2016 cycle of the North American Contact Dermatitis Group (NACDG) patch testing results, MI was found to be positive in 13.4% of patch tested patients (N=5597) and also had the highest significance-prevalence index number, a calculation that represents the relevance of positive reactions in relationship to prevalence.² In Europe, MI is banned in leave-on products and is allowed in rinse-off products in concentrations of up to 15 ppm. In the United States, the Cosmetic Ingredient Review panel concluded that MI is safe at a maximum concentration up to 100 ppm in rinse-off products and safe in leave-on products when formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.³

It is recommended that MI be patch tested at a concentration of 2000 ppm (0.2% aqueous).⁴ Testing at lower concentrations may result in missed positives. In addition, it should be noted that MCI/MI is present in the T.R.U.E. Test (SmartPractice), but MI alone is not.

Sources of MI Exposure

The first few case reports of MI contact allergy were associated with occupational exposures. In 2004, Isaksson et al⁵ reported 2 cases of MI allergy following exposure to wallpaper glue and a chemical burn from a biocide, respectively. Soon after, Thyssen et al⁶ reported 4 occupational cases of MI allergy at a paint manufacturing plant.

An early case series of MI contact allergy associated with personal care products was published in 2010 in which the authors described adults with ACD from wet wipes and a makeup remover that contained MI.⁷ A more recent report indicated that MI is now an infrequent ingredient in wet wipes but is still found in a wide variety of household and personal care products.⁸ A 2017 query of the American Contact Dermatitis Society’s Contact Allergy Management Program (CAMP) database revealed that 12.9% of all products contained MI. Furthermore, CAMP data revealed that MI was the most commonly found preservative in both hair care and household products.⁹ An additional CAMP database study revealed that 53% of shampoos and 45% of conditioners contained MI, and it also was commonly found in hair dyes, soaps and cleansers, hand cleaners and sanitizers, vaginal hygiene products, sunscreens, and moisturizers.¹⁰

Household products represent an important source of MI exposure. A chemical analysis of water-based paints identified the presence of isothiazolinones. Contact allergy from isothiazolinones in paint can present as either direct or airborne-pattern contact dermatitis.¹¹ Sodium bisulfite has been used to inactivate MCI/MI in wall paint and could be utilized in severe cases of airborne contact dermatitis.¹² Off-gassing may take up to 5.5 weeks before the paint cures and the isothiazolinone level decreases.¹³ A 2016 analysis of household products in the CAMP database revealed that MI commonly was found in dishwashing soap (64%), followed by household cleaners (47%), laundry softeners/additives (30%), surface disinfectants (27%), and laundry detergents (13%).¹⁰ Because certain chemical ingredients are not always listed on household product labels, patients with MI contact allergy may be at higher risk for unanticipated exposure to this allergen.

Dear reader, we know that you know all of this. We know that you have been watching the MI epidemic and have followed its every turn. But something that may be new to you are the unique MI exposures identified over the last several years.

In 2017, MI was identified in the glue used to affix 3 layers of the upper portion of a shoe.¹⁴ In addition, a recent chemical analysis of US consumer adhesives confirmed the presence of isothiazolinones in 50% (19/38) of products; 44.7% (17/38) specifically contained MI.¹⁵ Slime, the sticky play substance that children concoct out of household materials, has caused ACD, and not surprisingly, MI has been identified as a culprit allergen. In one case report, contact allergy was caused by MI present in a slime mixture made up of laundry detergent, dish soap, shampoo, and hand cream.¹⁶ In another case series, 3 children with MI contact allergy had played with slime that included dishwashing liquid, which contained MI, along with polyvinyl acetate glue and liquid soap components.¹⁷ Another case report documented slime made from MI-containing school glue as the source of ACD.¹⁸ Isothiazolinones also have been identified as causative allergens in “noise putty,” another homemade play item.¹⁹

Additionally, there has been a report of contact allergy to MI in a designer eyeglass frame.²⁰ There also have been several documented cases of ACD to MCI/MI aerosolized from water used during ironing.^21,22

There also have been several reports of photoaggravated ACD and possible photoallergic contact dermatitis from MI.^23,24 In such cases, patients also may have transient photosensitivity even when MI exposure is discontinued; therefore, MI should be considered for inclusion in photopatch test panels when relevant.

Methylisothiazolinone contact allergy also should be considered for products that do not list MI on the label, which presents another potential exposure. In products that do not list MI as an ingredient on the label, its presence may be due to inclusion of the preservative in raw materials used in production. For example, a patient who reacted to a facial mask gel had a positive patch test reaction to MI, the facial mask gel, and sodium hyaluronate, the raw ingredient in the gel. Further analysis revealed that MI was unexpectedly present in the sodium hyaluronate.²⁵ Similar scenarios have been reported in association with facial wet wipes,²⁶ an exfoliating facial sponge,²⁷ and a polyurethane sponge from a wound vacuum pump,²⁸ among others.

Other Isothiazolinones

Other isothiazolinones also are known to cause ACD, albeit less commonly than MI. Benzisothiazolinone has been identified in glues, cleaning agents, paints, and industrial chemicals; unlike MI, the presence of BIT is infrequent in personal care products.^15,29 This chemical is not commonly included in patch test screening series in the United States but is currently present in the NACDG screening series as BIT 0.1% in petrolatum.

Octylisothiazolinone (OIT) has been reported in leather furniture, belts, shoes, and watchbands, as well as industrial chemicals.^30,31 Similar to BIT, OIT is not commonly tested in screening series in the United States; the NACDG tests this chemical as OIT 0.025% in petrolatum.

The cross-reaction patterns between the isothiazolinones remain uncertain. A study in mice supported cross-reactivity between MI, OIT, and BIT³²; however, several clinical epidemiologic studies suggested that although there is evidence that there may be cross-reactivity between OIT and MI, concomitant positive BIT and MI reactions more likely represent cosensitization.^33-35

Final Interpretation

Methylisothiazolinone continues to have high positive patch test rates in North American patch test populations and should be tested at a concentration of 2000 ppm (0.2% aqueous). Methylisothiazolinone may now be rare in wet wipes, but it is still present in numerous personal care products including hair care products, liquid soaps, and cleaning products. Novel exposures to MI include paint, slime, and glues. It also is important to remember that MI can cause photoaggravated or photoallergic contact dermatitis and might be a worthy addition to photopatch test trays. Finally, keep a look out for BIT and OIT, which may be present in industrial chemicals, glues, paints, cleaning products, and leather items.

Unless you have been living under a rock, you probably already know that the preservative methylisothiazolinone (MI) has caused an epidemic of allergic contact dermatitis (ACD) and was named the 2013 American Contact Dermatitis Society Allergen of the Year.¹ Methylisothiazolinone is not new on the market, but its solo use as a preservative is relatively new. In this article, we review the emergence of MI as a common allergen, discuss North American MI patch test results, and describe common and uncommon sources of MI exposure. We also explore the related isothiazolinones, benzisothiazolinone (BIT) and octylisothiazolinone (OIT).

Background

Methylchloroisothiazolinone (MCI) and MI have been utilized as a preservative in a 3:1 ratio since the 1980s. In 2005, MI was first used alone as a preservative in personal care products in concentrations of up to 100 ppm, which represented a 25-fold increase in exposure to MI in personal care products and thus unleashed an epidemic of ACD.¹ In the 2015 to 2016 cycle of the North American Contact Dermatitis Group (NACDG) patch testing results, MI was found to be positive in 13.4% of patch tested patients (N=5597) and also had the highest significance-prevalence index number, a calculation that represents the relevance of positive reactions in relationship to prevalence.² In Europe, MI is banned in leave-on products and is allowed in rinse-off products in concentrations of up to 15 ppm. In the United States, the Cosmetic Ingredient Review panel concluded that MI is safe at a maximum concentration up to 100 ppm in rinse-off products and safe in leave-on products when formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.³

It is recommended that MI be patch tested at a concentration of 2000 ppm (0.2% aqueous).⁴ Testing at lower concentrations may result in missed positives. In addition, it should be noted that MCI/MI is present in the T.R.U.E. Test (SmartPractice), but MI alone is not.

Sources of MI Exposure

The first few case reports of MI contact allergy were associated with occupational exposures. In 2004, Isaksson et al⁵ reported 2 cases of MI allergy following exposure to wallpaper glue and a chemical burn from a biocide, respectively. Soon after, Thyssen et al⁶ reported 4 occupational cases of MI allergy at a paint manufacturing plant.

An early case series of MI contact allergy associated with personal care products was published in 2010 in which the authors described adults with ACD from wet wipes and a makeup remover that contained MI.⁷ A more recent report indicated that MI is now an infrequent ingredient in wet wipes but is still found in a wide variety of household and personal care products.⁸ A 2017 query of the American Contact Dermatitis Society’s Contact Allergy Management Program (CAMP) database revealed that 12.9% of all products contained MI. Furthermore, CAMP data revealed that MI was the most commonly found preservative in both hair care and household products.⁹ An additional CAMP database study revealed that 53% of shampoos and 45% of conditioners contained MI, and it also was commonly found in hair dyes, soaps and cleansers, hand cleaners and sanitizers, vaginal hygiene products, sunscreens, and moisturizers.¹⁰

Household products represent an important source of MI exposure. A chemical analysis of water-based paints identified the presence of isothiazolinones. Contact allergy from isothiazolinones in paint can present as either direct or airborne-pattern contact dermatitis.¹¹ Sodium bisulfite has been used to inactivate MCI/MI in wall paint and could be utilized in severe cases of airborne contact dermatitis.¹² Off-gassing may take up to 5.5 weeks before the paint cures and the isothiazolinone level decreases.¹³ A 2016 analysis of household products in the CAMP database revealed that MI commonly was found in dishwashing soap (64%), followed by household cleaners (47%), laundry softeners/additives (30%), surface disinfectants (27%), and laundry detergents (13%).¹⁰ Because certain chemical ingredients are not always listed on household product labels, patients with MI contact allergy may be at higher risk for unanticipated exposure to this allergen.

Dear reader, we know that you know all of this. We know that you have been watching the MI epidemic and have followed its every turn. But something that may be new to you are the unique MI exposures identified over the last several years.

In 2017, MI was identified in the glue used to affix 3 layers of the upper portion of a shoe.¹⁴ In addition, a recent chemical analysis of US consumer adhesives confirmed the presence of isothiazolinones in 50% (19/38) of products; 44.7% (17/38) specifically contained MI.¹⁵ Slime, the sticky play substance that children concoct out of household materials, has caused ACD, and not surprisingly, MI has been identified as a culprit allergen. In one case report, contact allergy was caused by MI present in a slime mixture made up of laundry detergent, dish soap, shampoo, and hand cream.¹⁶ In another case series, 3 children with MI contact allergy had played with slime that included dishwashing liquid, which contained MI, along with polyvinyl acetate glue and liquid soap components.¹⁷ Another case report documented slime made from MI-containing school glue as the source of ACD.¹⁸ Isothiazolinones also have been identified as causative allergens in “noise putty,” another homemade play item.¹⁹

Additionally, there has been a report of contact allergy to MI in a designer eyeglass frame.²⁰ There also have been several documented cases of ACD to MCI/MI aerosolized from water used during ironing.^21,22

There also have been several reports of photoaggravated ACD and possible photoallergic contact dermatitis from MI.^23,24 In such cases, patients also may have transient photosensitivity even when MI exposure is discontinued; therefore, MI should be considered for inclusion in photopatch test panels when relevant.

Methylisothiazolinone contact allergy also should be considered for products that do not list MI on the label, which presents another potential exposure. In products that do not list MI as an ingredient on the label, its presence may be due to inclusion of the preservative in raw materials used in production. For example, a patient who reacted to a facial mask gel had a positive patch test reaction to MI, the facial mask gel, and sodium hyaluronate, the raw ingredient in the gel. Further analysis revealed that MI was unexpectedly present in the sodium hyaluronate.²⁵ Similar scenarios have been reported in association with facial wet wipes,²⁶ an exfoliating facial sponge,²⁷ and a polyurethane sponge from a wound vacuum pump,²⁸ among others.

Other Isothiazolinones

Other isothiazolinones also are known to cause ACD, albeit less commonly than MI. Benzisothiazolinone has been identified in glues, cleaning agents, paints, and industrial chemicals; unlike MI, the presence of BIT is infrequent in personal care products.^15,29 This chemical is not commonly included in patch test screening series in the United States but is currently present in the NACDG screening series as BIT 0.1% in petrolatum.

Octylisothiazolinone (OIT) has been reported in leather furniture, belts, shoes, and watchbands, as well as industrial chemicals.^30,31 Similar to BIT, OIT is not commonly tested in screening series in the United States; the NACDG tests this chemical as OIT 0.025% in petrolatum.

The cross-reaction patterns between the isothiazolinones remain uncertain. A study in mice supported cross-reactivity between MI, OIT, and BIT³²; however, several clinical epidemiologic studies suggested that although there is evidence that there may be cross-reactivity between OIT and MI, concomitant positive BIT and MI reactions more likely represent cosensitization.^33-35

Final Interpretation

Methylisothiazolinone continues to have high positive patch test rates in North American patch test populations and should be tested at a concentration of 2000 ppm (0.2% aqueous). Methylisothiazolinone may now be rare in wet wipes, but it is still present in numerous personal care products including hair care products, liquid soaps, and cleaning products. Novel exposures to MI include paint, slime, and glues. It also is important to remember that MI can cause photoaggravated or photoallergic contact dermatitis and might be a worthy addition to photopatch test trays. Finally, keep a look out for BIT and OIT, which may be present in industrial chemicals, glues, paints, cleaning products, and leather items.

Unless you have been living under a rock, you probably already know that the preservative methylisothiazolinone (MI) has caused an epidemic of allergic contact dermatitis (ACD) and was named the 2013 American Contact Dermatitis Society Allergen of the Year.¹ Methylisothiazolinone is not new on the market, but its solo use as a preservative is relatively new. In this article, we review the emergence of MI as a common allergen, discuss North American MI patch test results, and describe common and uncommon sources of MI exposure. We also explore the related isothiazolinones, benzisothiazolinone (BIT) and octylisothiazolinone (OIT).

Background

Methylchloroisothiazolinone (MCI) and MI have been utilized as a preservative in a 3:1 ratio since the 1980s. In 2005, MI was first used alone as a preservative in personal care products in concentrations of up to 100 ppm, which represented a 25-fold increase in exposure to MI in personal care products and thus unleashed an epidemic of ACD.¹ In the 2015 to 2016 cycle of the North American Contact Dermatitis Group (NACDG) patch testing results, MI was found to be positive in 13.4% of patch tested patients (N=5597) and also had the highest significance-prevalence index number, a calculation that represents the relevance of positive reactions in relationship to prevalence.² In Europe, MI is banned in leave-on products and is allowed in rinse-off products in concentrations of up to 15 ppm. In the United States, the Cosmetic Ingredient Review panel concluded that MI is safe at a maximum concentration up to 100 ppm in rinse-off products and safe in leave-on products when formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.³

It is recommended that MI be patch tested at a concentration of 2000 ppm (0.2% aqueous).⁴ Testing at lower concentrations may result in missed positives. In addition, it should be noted that MCI/MI is present in the T.R.U.E. Test (SmartPractice), but MI alone is not.

Sources of MI Exposure

The first few case reports of MI contact allergy were associated with occupational exposures. In 2004, Isaksson et al⁵ reported 2 cases of MI allergy following exposure to wallpaper glue and a chemical burn from a biocide, respectively. Soon after, Thyssen et al⁶ reported 4 occupational cases of MI allergy at a paint manufacturing plant.

An early case series of MI contact allergy associated with personal care products was published in 2010 in which the authors described adults with ACD from wet wipes and a makeup remover that contained MI.⁷ A more recent report indicated that MI is now an infrequent ingredient in wet wipes but is still found in a wide variety of household and personal care products.⁸ A 2017 query of the American Contact Dermatitis Society’s Contact Allergy Management Program (CAMP) database revealed that 12.9% of all products contained MI. Furthermore, CAMP data revealed that MI was the most commonly found preservative in both hair care and household products.⁹ An additional CAMP database study revealed that 53% of shampoos and 45% of conditioners contained MI, and it also was commonly found in hair dyes, soaps and cleansers, hand cleaners and sanitizers, vaginal hygiene products, sunscreens, and moisturizers.¹⁰

Household products represent an important source of MI exposure. A chemical analysis of water-based paints identified the presence of isothiazolinones. Contact allergy from isothiazolinones in paint can present as either direct or airborne-pattern contact dermatitis.¹¹ Sodium bisulfite has been used to inactivate MCI/MI in wall paint and could be utilized in severe cases of airborne contact dermatitis.¹² Off-gassing may take up to 5.5 weeks before the paint cures and the isothiazolinone level decreases.¹³ A 2016 analysis of household products in the CAMP database revealed that MI commonly was found in dishwashing soap (64%), followed by household cleaners (47%), laundry softeners/additives (30%), surface disinfectants (27%), and laundry detergents (13%).¹⁰ Because certain chemical ingredients are not always listed on household product labels, patients with MI contact allergy may be at higher risk for unanticipated exposure to this allergen.

Dear reader, we know that you know all of this. We know that you have been watching the MI epidemic and have followed its every turn. But something that may be new to you are the unique MI exposures identified over the last several years.

In 2017, MI was identified in the glue used to affix 3 layers of the upper portion of a shoe.¹⁴ In addition, a recent chemical analysis of US consumer adhesives confirmed the presence of isothiazolinones in 50% (19/38) of products; 44.7% (17/38) specifically contained MI.¹⁵ Slime, the sticky play substance that children concoct out of household materials, has caused ACD, and not surprisingly, MI has been identified as a culprit allergen. In one case report, contact allergy was caused by MI present in a slime mixture made up of laundry detergent, dish soap, shampoo, and hand cream.¹⁶ In another case series, 3 children with MI contact allergy had played with slime that included dishwashing liquid, which contained MI, along with polyvinyl acetate glue and liquid soap components.¹⁷ Another case report documented slime made from MI-containing school glue as the source of ACD.¹⁸ Isothiazolinones also have been identified as causative allergens in “noise putty,” another homemade play item.¹⁹

Additionally, there has been a report of contact allergy to MI in a designer eyeglass frame.²⁰ There also have been several documented cases of ACD to MCI/MI aerosolized from water used during ironing.^21,22

There also have been several reports of photoaggravated ACD and possible photoallergic contact dermatitis from MI.^23,24 In such cases, patients also may have transient photosensitivity even when MI exposure is discontinued; therefore, MI should be considered for inclusion in photopatch test panels when relevant.

Methylisothiazolinone contact allergy also should be considered for products that do not list MI on the label, which presents another potential exposure. In products that do not list MI as an ingredient on the label, its presence may be due to inclusion of the preservative in raw materials used in production. For example, a patient who reacted to a facial mask gel had a positive patch test reaction to MI, the facial mask gel, and sodium hyaluronate, the raw ingredient in the gel. Further analysis revealed that MI was unexpectedly present in the sodium hyaluronate.²⁵ Similar scenarios have been reported in association with facial wet wipes,²⁶ an exfoliating facial sponge,²⁷ and a polyurethane sponge from a wound vacuum pump,²⁸ among others.

Other Isothiazolinones

Other isothiazolinones also are known to cause ACD, albeit less commonly than MI. Benzisothiazolinone has been identified in glues, cleaning agents, paints, and industrial chemicals; unlike MI, the presence of BIT is infrequent in personal care products.^15,29 This chemical is not commonly included in patch test screening series in the United States but is currently present in the NACDG screening series as BIT 0.1% in petrolatum.

Octylisothiazolinone (OIT) has been reported in leather furniture, belts, shoes, and watchbands, as well as industrial chemicals.^30,31 Similar to BIT, OIT is not commonly tested in screening series in the United States; the NACDG tests this chemical as OIT 0.025% in petrolatum.

The cross-reaction patterns between the isothiazolinones remain uncertain. A study in mice supported cross-reactivity between MI, OIT, and BIT³²; however, several clinical epidemiologic studies suggested that although there is evidence that there may be cross-reactivity between OIT and MI, concomitant positive BIT and MI reactions more likely represent cosensitization.^33-35

Final Interpretation

Methylisothiazolinone continues to have high positive patch test rates in North American patch test populations and should be tested at a concentration of 2000 ppm (0.2% aqueous). Methylisothiazolinone may now be rare in wet wipes, but it is still present in numerous personal care products including hair care products, liquid soaps, and cleaning products. Novel exposures to MI include paint, slime, and glues. It also is important to remember that MI can cause photoaggravated or photoallergic contact dermatitis and might be a worthy addition to photopatch test trays. Finally, keep a look out for BIT and OIT, which may be present in industrial chemicals, glues, paints, cleaning products, and leather items.

NEW YORK – Flaking, itchy, swollen lips represent more than a cosmetic problem. Eczematous cheilitis can interfere with communication and nutrition, but patients may be slow to seek help, Bethanee Schlosser, MD, PhD, said at the American Academy of Dermatology summer meeting.

One of the challenges in helping patients with lip problems is that lips are constantly in motion and constantly interacting with the outside world, said Dr. Schlosser, of the department of dermatology, Northwestern University, Chicago. There’s ongoing low-level trauma with phonation, eating, drinking, and general environmental exposure, she said. Eczematous cheilitis will present with scaling and erythema of the vermilion lips, with lower lip involvement often more pronounced than symptoms on the upper lip. Fissuring and erosion are sometimes, but not always, present as well.

In addition to flaking and redness, Dr. Schlosser noted that patients will complain of dry lips, irritation, itching, and sometimes tingling.

Sorting out the etiology of eczematous cheilitis requires a thorough history. “Ask about habits, such as lip licking, picking, or biting,” she said. Recent dental work, braces, or other appliances for alignment or temporomandibular joint problems can introduce both mechanical irritation and potential allergens, and even musical instruments can be culprits, such as when an oboe reed causes an allergic reaction.

Personal hygiene products, cosmetics, gum chewing, and candy consumption can be the irritant culprits, noted Dr. Schlosser. Careful questioning of patients and examination of the products used can provide clues, since dyes and pigments in cosmetics and gum may provoke reactions.

History taking should also include questions about tobacco in all forms, marijuana, and prescription medication, which can cause lip problems. And it’s important to ask about skin disease in general, to determine if symptoms are present in other anatomic locations, and to ask about any family history of skin disease, she said.

Endogenous contributors can include true atopic dermatitis, psoriasis, and nutritional deficiencies. Psoriatic cheilitis can have prominent crusting and exfoliation. In a Brazilian study that evaluated patents with cutaneous psoriasis and age-, race-, and sex-matched controls with no history of skin disease, psoriasis was associated with geographic tongue, with an odds ratio of 5.0 (95% CI 1.5-16.8). Geographic stomatitis can also be seen, said Dr. Schlosser. Tongue fissures were also more common among those with psoriasis cheilitis (OR 2.7, 95% confidence interval, 1.3-5.6) in the same study (Med Oral Patol Oral Cir Bucal. 2009 Aug 1;14[8]:e371-5).

For psoriatic cheilitis, looking beyond the lips can help refine the diagnosis, she noted. There may be intra-oral signs or signs of extra-oral involvement, especially on the scalp, ears, and genitalia. Koebnerization may be difficult to detect on the lips, but may be present elsewhere. A family history of psoriasis may also tip the scales toward this diagnosis.

Exogenous causes of eczematous cheilitis are much more common and can include contact with irritants and allergens, factitial cheilitis, and cheilitis medicamentosa, Dr Schlosser pointed out.

Allergic contact dermatitis can come from local exposure (to cosmetics and other personal care items, for example) or from incidental exposures. Components of saliva can become concentrated when saliva dries outside the oral cavity, so for chronic lip lickers, saliva alone can be sufficiently irritating to provoke a cheilitis, Dr. Schlosser said.

Transfer of an irritant or allergen is also possible from other body sites, as when a nail-chewer develops allergic cheilitis from an ingredient in nail polish. Transfer from products used on other facial areas and the hair is also possible, as is “connubial transfer,” when an allergen is transferred from an intimate partner.

Cutaneous patch tests can be helpful in pinpointing the offending agent, or agents, according to Dr. Schlosser. She cited a study of 91 patients (77% of whom were female) who underwent patch testing for eczematous cheilitis. The researchers determined that 45% of patients had allergic contact cheilitis (Int J Dermatol. 2016 Jul;55[7]:e386-91).

The patch testing revealed that fragrances, balsam of Peru (Myroxylon pereirae resin), preservatives, and even metals such as nickel and gold were common allergens. The findings echo those in another database review that showed fragrances, M. pereirae, and nickel as the top three allergens on patch testing for lip cheilitis.

Dr. Schlosser said that the most common offending sources are lipsticks, makeup, other cosmetic products, and moisturizer, which are responsible for 10% or more of reactions.

Whatever the etiology, the treatment of eczematous cheilitis can be divided conceptually into two phases. During the induction phase, use of a low- to mid-potency topical corticosteroid ointment quiets inflammation. Examples include alclometasone 0.05%, desonide 0.05%, fluticasone 0.005%, or triamcinolone 0.1%. “Ointment formulations are preferred,” said Dr. Schlosser, since they won’t dissolve so easily with lip licking and will adhere well to the surface of the vermilion lip.

Next, a topical calcineurin inhibitor such as tacrolimus 0.1% can be used for maintenance. Other topical medications, especially topical anesthetics, should be used with caution, she said.

For psoriatic cheilitis, induction with 5% salicylic acid ointment can be followed by the topical calcineurin inhibitor phase, said Dr. Schlosser.

Dr. Schlosser disclosed financial relationships with Beiersdorf, Decision Support in Medicine, and UpToDate.

[email protected]

NEW YORK – Flaking, itchy, swollen lips represent more than a cosmetic problem. Eczematous cheilitis can interfere with communication and nutrition, but patients may be slow to seek help, Bethanee Schlosser, MD, PhD, said at the American Academy of Dermatology summer meeting.

One of the challenges in helping patients with lip problems is that lips are constantly in motion and constantly interacting with the outside world, said Dr. Schlosser, of the department of dermatology, Northwestern University, Chicago. There’s ongoing low-level trauma with phonation, eating, drinking, and general environmental exposure, she said. Eczematous cheilitis will present with scaling and erythema of the vermilion lips, with lower lip involvement often more pronounced than symptoms on the upper lip. Fissuring and erosion are sometimes, but not always, present as well.

In addition to flaking and redness, Dr. Schlosser noted that patients will complain of dry lips, irritation, itching, and sometimes tingling.

Sorting out the etiology of eczematous cheilitis requires a thorough history. “Ask about habits, such as lip licking, picking, or biting,” she said. Recent dental work, braces, or other appliances for alignment or temporomandibular joint problems can introduce both mechanical irritation and potential allergens, and even musical instruments can be culprits, such as when an oboe reed causes an allergic reaction.

Personal hygiene products, cosmetics, gum chewing, and candy consumption can be the irritant culprits, noted Dr. Schlosser. Careful questioning of patients and examination of the products used can provide clues, since dyes and pigments in cosmetics and gum may provoke reactions.

History taking should also include questions about tobacco in all forms, marijuana, and prescription medication, which can cause lip problems. And it’s important to ask about skin disease in general, to determine if symptoms are present in other anatomic locations, and to ask about any family history of skin disease, she said.

Endogenous contributors can include true atopic dermatitis, psoriasis, and nutritional deficiencies. Psoriatic cheilitis can have prominent crusting and exfoliation. In a Brazilian study that evaluated patents with cutaneous psoriasis and age-, race-, and sex-matched controls with no history of skin disease, psoriasis was associated with geographic tongue, with an odds ratio of 5.0 (95% CI 1.5-16.8). Geographic stomatitis can also be seen, said Dr. Schlosser. Tongue fissures were also more common among those with psoriasis cheilitis (OR 2.7, 95% confidence interval, 1.3-5.6) in the same study (Med Oral Patol Oral Cir Bucal. 2009 Aug 1;14[8]:e371-5).

For psoriatic cheilitis, looking beyond the lips can help refine the diagnosis, she noted. There may be intra-oral signs or signs of extra-oral involvement, especially on the scalp, ears, and genitalia. Koebnerization may be difficult to detect on the lips, but may be present elsewhere. A family history of psoriasis may also tip the scales toward this diagnosis.

Exogenous causes of eczematous cheilitis are much more common and can include contact with irritants and allergens, factitial cheilitis, and cheilitis medicamentosa, Dr Schlosser pointed out.

Allergic contact dermatitis can come from local exposure (to cosmetics and other personal care items, for example) or from incidental exposures. Components of saliva can become concentrated when saliva dries outside the oral cavity, so for chronic lip lickers, saliva alone can be sufficiently irritating to provoke a cheilitis, Dr. Schlosser said.

Transfer of an irritant or allergen is also possible from other body sites, as when a nail-chewer develops allergic cheilitis from an ingredient in nail polish. Transfer from products used on other facial areas and the hair is also possible, as is “connubial transfer,” when an allergen is transferred from an intimate partner.

Cutaneous patch tests can be helpful in pinpointing the offending agent, or agents, according to Dr. Schlosser. She cited a study of 91 patients (77% of whom were female) who underwent patch testing for eczematous cheilitis. The researchers determined that 45% of patients had allergic contact cheilitis (Int J Dermatol. 2016 Jul;55[7]:e386-91).

The patch testing revealed that fragrances, balsam of Peru (Myroxylon pereirae resin), preservatives, and even metals such as nickel and gold were common allergens. The findings echo those in another database review that showed fragrances, M. pereirae, and nickel as the top three allergens on patch testing for lip cheilitis.

Dr. Schlosser said that the most common offending sources are lipsticks, makeup, other cosmetic products, and moisturizer, which are responsible for 10% or more of reactions.

Whatever the etiology, the treatment of eczematous cheilitis can be divided conceptually into two phases. During the induction phase, use of a low- to mid-potency topical corticosteroid ointment quiets inflammation. Examples include alclometasone 0.05%, desonide 0.05%, fluticasone 0.005%, or triamcinolone 0.1%. “Ointment formulations are preferred,” said Dr. Schlosser, since they won’t dissolve so easily with lip licking and will adhere well to the surface of the vermilion lip.

Next, a topical calcineurin inhibitor such as tacrolimus 0.1% can be used for maintenance. Other topical medications, especially topical anesthetics, should be used with caution, she said.

For psoriatic cheilitis, induction with 5% salicylic acid ointment can be followed by the topical calcineurin inhibitor phase, said Dr. Schlosser.

Dr. Schlosser disclosed financial relationships with Beiersdorf, Decision Support in Medicine, and UpToDate.

[email protected]

NEW YORK – Flaking, itchy, swollen lips represent more than a cosmetic problem. Eczematous cheilitis can interfere with communication and nutrition, but patients may be slow to seek help, Bethanee Schlosser, MD, PhD, said at the American Academy of Dermatology summer meeting.

One of the challenges in helping patients with lip problems is that lips are constantly in motion and constantly interacting with the outside world, said Dr. Schlosser, of the department of dermatology, Northwestern University, Chicago. There’s ongoing low-level trauma with phonation, eating, drinking, and general environmental exposure, she said. Eczematous cheilitis will present with scaling and erythema of the vermilion lips, with lower lip involvement often more pronounced than symptoms on the upper lip. Fissuring and erosion are sometimes, but not always, present as well.

In addition to flaking and redness, Dr. Schlosser noted that patients will complain of dry lips, irritation, itching, and sometimes tingling.

Sorting out the etiology of eczematous cheilitis requires a thorough history. “Ask about habits, such as lip licking, picking, or biting,” she said. Recent dental work, braces, or other appliances for alignment or temporomandibular joint problems can introduce both mechanical irritation and potential allergens, and even musical instruments can be culprits, such as when an oboe reed causes an allergic reaction.

Personal hygiene products, cosmetics, gum chewing, and candy consumption can be the irritant culprits, noted Dr. Schlosser. Careful questioning of patients and examination of the products used can provide clues, since dyes and pigments in cosmetics and gum may provoke reactions.

History taking should also include questions about tobacco in all forms, marijuana, and prescription medication, which can cause lip problems. And it’s important to ask about skin disease in general, to determine if symptoms are present in other anatomic locations, and to ask about any family history of skin disease, she said.

Endogenous contributors can include true atopic dermatitis, psoriasis, and nutritional deficiencies. Psoriatic cheilitis can have prominent crusting and exfoliation. In a Brazilian study that evaluated patents with cutaneous psoriasis and age-, race-, and sex-matched controls with no history of skin disease, psoriasis was associated with geographic tongue, with an odds ratio of 5.0 (95% CI 1.5-16.8). Geographic stomatitis can also be seen, said Dr. Schlosser. Tongue fissures were also more common among those with psoriasis cheilitis (OR 2.7, 95% confidence interval, 1.3-5.6) in the same study (Med Oral Patol Oral Cir Bucal. 2009 Aug 1;14[8]:e371-5).

For psoriatic cheilitis, looking beyond the lips can help refine the diagnosis, she noted. There may be intra-oral signs or signs of extra-oral involvement, especially on the scalp, ears, and genitalia. Koebnerization may be difficult to detect on the lips, but may be present elsewhere. A family history of psoriasis may also tip the scales toward this diagnosis.

Exogenous causes of eczematous cheilitis are much more common and can include contact with irritants and allergens, factitial cheilitis, and cheilitis medicamentosa, Dr Schlosser pointed out.

Allergic contact dermatitis can come from local exposure (to cosmetics and other personal care items, for example) or from incidental exposures. Components of saliva can become concentrated when saliva dries outside the oral cavity, so for chronic lip lickers, saliva alone can be sufficiently irritating to provoke a cheilitis, Dr. Schlosser said.

Transfer of an irritant or allergen is also possible from other body sites, as when a nail-chewer develops allergic cheilitis from an ingredient in nail polish. Transfer from products used on other facial areas and the hair is also possible, as is “connubial transfer,” when an allergen is transferred from an intimate partner.

Cutaneous patch tests can be helpful in pinpointing the offending agent, or agents, according to Dr. Schlosser. She cited a study of 91 patients (77% of whom were female) who underwent patch testing for eczematous cheilitis. The researchers determined that 45% of patients had allergic contact cheilitis (Int J Dermatol. 2016 Jul;55[7]:e386-91).

The patch testing revealed that fragrances, balsam of Peru (Myroxylon pereirae resin), preservatives, and even metals such as nickel and gold were common allergens. The findings echo those in another database review that showed fragrances, M. pereirae, and nickel as the top three allergens on patch testing for lip cheilitis.

Dr. Schlosser said that the most common offending sources are lipsticks, makeup, other cosmetic products, and moisturizer, which are responsible for 10% or more of reactions.

Whatever the etiology, the treatment of eczematous cheilitis can be divided conceptually into two phases. During the induction phase, use of a low- to mid-potency topical corticosteroid ointment quiets inflammation. Examples include alclometasone 0.05%, desonide 0.05%, fluticasone 0.005%, or triamcinolone 0.1%. “Ointment formulations are preferred,” said Dr. Schlosser, since they won’t dissolve so easily with lip licking and will adhere well to the surface of the vermilion lip.

Next, a topical calcineurin inhibitor such as tacrolimus 0.1% can be used for maintenance. Other topical medications, especially topical anesthetics, should be used with caution, she said.

For psoriatic cheilitis, induction with 5% salicylic acid ointment can be followed by the topical calcineurin inhibitor phase, said Dr. Schlosser.

Dr. Schlosser disclosed financial relationships with Beiersdorf, Decision Support in Medicine, and UpToDate.

[email protected]

AUSTIN – Not long ago, Rajani Katta, MD, received a text message from a friend who expressed concern about a rash that developed in the underarm of her teenage daughter.

The culprit turned out to be the lavender essential oil contained in an “all natural” deodorant that her daughter had recently switched to – a storyline that Dr. Katta encounters with increasing frequency in her role as clinical professor of dermatology at the University of Texas Health Science Center at Houston.

“Some people may think that you can’t get an allergic reaction to natural products, but we are seeing many allergic reactions to essential oils,” Dr. Katta said at the annual meeting of the Society for Pediatric Dermatology. “When you talk about a natural allergy, it is more likely to occur if your skin barrier is compromised, so I think that’s why we’re seeing it, especially in young girls in the underarm area. If you shave the underarm, you impair that skin barrier and you’re more likely to develop a reaction to something you’re using over it.”

Her list of recommended deodorants includes Almay Roll-On Antiperspirant & Deodorant, Crystal Body Deodorant Stick, Crystal Roll-On Body Deodorant, Vanicream Deodorant for Sensitive Skin (aluminum-free), Vanicream Antiperspirant/Deodorant, and CertainDri Clinical Strength Roll-On. They are fragrance-free and lack propylene glycol, which is a common allergen.

Increasingly, essential oils are being added to lip balms and toothpastes, said Dr. Katta, who is also author of the 2018 book “Glow: The Dermatologist’s Guide to a Whole Foods Younger Skin Diet.” She recalled one patient who presented with chronic chapped lips. “It doesn’t matter how many lip glosses I try; it just keeps getting worse,” the patient told her. The likely culprit turned out to be ingredients contained in flavored lip balm from EOS. Reports of blistering and cracking of the lips from use of the products prompted a class action lawsuit and a notice to consumers from the Food and Drug Administration.

Another patient presented with cracked lips after switching to an “all natural” toothpaste that was labeled “gluten free.”

“It looked great,” Dr. Katta recalled. “Unfortunately it was not flavoring free. She reacted to multiple essential oils, including tea tree oil, contained in the toothpaste. This is being added to a number of toothpastes, and I think we’re going to see more of these types of reactions.”

Other toothpastes contain balsam of Peru, “which is consistently one of the top allergens in patch test clinics,” she said. “One of the components of balsam of Peru is a cinnamon compound, which can be an issue.”

Dr. Katta advises her patients to use Vaseline petroleum jelly as a lip balm and recommends Tom’s of Maine Silly Strawberry Flavor (this flavor only) toothpaste for children.

A few years ago, a teenager presented to Dr. Katta with intense bullae on the dorsum of the foot after wearing shoes without socks. “She was wearing white canvas Keds, which looked very innocuous,” she said. Patch testing revealed that the teen reacted to four different rubber accelerators. “When we contacted the company, they [acknowledged] using rubber cement to make the canvas Keds,” Dr. Katta said. “Rubber cement is an adhesive and it does contain rubber accelerators. Later, I saw two cases of children who had walked around all day at the amusement park wearing their Sperry Topsiders without any socks. We couldn’t get any information from that manufacturer, but I suspect that they also use a rubber-based glue to make those shoes.” She characterized shoes as “a real setup for a foot allergy because you have friction, sweat that’s pulling allergen out of an object, and sweat is carrying it over, especially to the dorsum of the foot.”


Dr. Katta has also noticed an uptick in the number of young patients who develop allergic reactions to dyes used to make workout clothing. “If you ever see rashes that do not involve the axillary vault but do have peraxillary accentuation, think textile allergy,” she said. “We’re seeing a lot of reactions to disperse blue clothing dyes. When you think about textile allergy from the dyes, it tends to be the blue and black clothing. It’s more likely in the setting of synthetic fabrics because they leach out dyes more easily, and it’s more likely in the setting of sweat because sweat helps pull allergen out. I’m seeing it a lot from sports uniforms and tight black leggings and tight sports bras that people are wearing. I’m also seeing some from bathing suits and swim shirts.”

Exposure to products containing the preservative methylisothiazolinone (MI) is also on the rise. It ranks as the second most frequent allergen for which the North American Contact Dermatitis Group is seeing positive results on patch testing, with rates of 13.4%. MI can be found in many skin care products and “probably about half of school glues, fabric glues, and craft glues,” Dr. Katta said. “Stick versus liquid doesn’t make a difference.” Children and teens often use craft glues, laundry detergents, and other products to create “slime” as a way to learn about viscosity, polymers, and chemical reactions. “Sometimes these children have sensitive skin, or they’re using it with prolonged contact, so they may be sensitizing themselves to the MI,” she said.

She concluded her remarks by noting that an increasing number of young patients are developing reactions to wearable medical devices such as insulin pumps and glucose monitors. “With this, the first thing to think about is frictional irritant dermatitis,” she said. “You can put Scanpor medical paper tape on people’s back for 48 hours straight to patch test them. Some people are incredibly reactive to the friction of just that tape. You also have to think about trapped allergen. One of my patients reacted to colophony, fragrance mix, and propylene glycol, all of which were contained in his skin care products. Some people are getting advice from other patients to use Mastisol liquid adhesive to help their glucose monitors stick better. Mastisol has a high rate of cross-reactivity with balsam of Peru, so it’s a fragrance allergen. That’s the first thing you want to ask patients about: what products they’re using.”

One of her patients thought she was reacting to adhesive tape on her skin, but in fact she was reacting to two different acrylates: ethylene glycol dimethacrylate (EGDMA) and hydroxyethyl methacrylate (HEMA). “I know about these allergens because I see reactions from butterfly needles in dialysis patients,” Dr. Katta explained. “What happens is, these acrylates are glues or plastics used somewhere else on the device, and they can migrate through barriers.”

In one published case, a 9-year-old boy developed a reaction to ethyl cyanoacrylate contained in a glucose sensor adhesive (Dermatitis. 2017; 28[4]:289-91). It never touched the boy’s skin directly but was presumed to migrate through that tape. “The bottom line is that acrylates may induce contact dermatitis even through perceived barriers,” she said. “Their use anywhere in medical devices may prove problematic.”

Dr. Katta reported that she is a member of the advisory board for Vichy Laboratories.
 

[email protected]

AUSTIN – Not long ago, Rajani Katta, MD, received a text message from a friend who expressed concern about a rash that developed in the underarm of her teenage daughter.

The culprit turned out to be the lavender essential oil contained in an “all natural” deodorant that her daughter had recently switched to – a storyline that Dr. Katta encounters with increasing frequency in her role as clinical professor of dermatology at the University of Texas Health Science Center at Houston.

“Some people may think that you can’t get an allergic reaction to natural products, but we are seeing many allergic reactions to essential oils,” Dr. Katta said at the annual meeting of the Society for Pediatric Dermatology. “When you talk about a natural allergy, it is more likely to occur if your skin barrier is compromised, so I think that’s why we’re seeing it, especially in young girls in the underarm area. If you shave the underarm, you impair that skin barrier and you’re more likely to develop a reaction to something you’re using over it.”

Her list of recommended deodorants includes Almay Roll-On Antiperspirant & Deodorant, Crystal Body Deodorant Stick, Crystal Roll-On Body Deodorant, Vanicream Deodorant for Sensitive Skin (aluminum-free), Vanicream Antiperspirant/Deodorant, and CertainDri Clinical Strength Roll-On. They are fragrance-free and lack propylene glycol, which is a common allergen.

Increasingly, essential oils are being added to lip balms and toothpastes, said Dr. Katta, who is also author of the 2018 book “Glow: The Dermatologist’s Guide to a Whole Foods Younger Skin Diet.” She recalled one patient who presented with chronic chapped lips. “It doesn’t matter how many lip glosses I try; it just keeps getting worse,” the patient told her. The likely culprit turned out to be ingredients contained in flavored lip balm from EOS. Reports of blistering and cracking of the lips from use of the products prompted a class action lawsuit and a notice to consumers from the Food and Drug Administration.

Another patient presented with cracked lips after switching to an “all natural” toothpaste that was labeled “gluten free.”

“It looked great,” Dr. Katta recalled. “Unfortunately it was not flavoring free. She reacted to multiple essential oils, including tea tree oil, contained in the toothpaste. This is being added to a number of toothpastes, and I think we’re going to see more of these types of reactions.”

Other toothpastes contain balsam of Peru, “which is consistently one of the top allergens in patch test clinics,” she said. “One of the components of balsam of Peru is a cinnamon compound, which can be an issue.”

Dr. Katta advises her patients to use Vaseline petroleum jelly as a lip balm and recommends Tom’s of Maine Silly Strawberry Flavor (this flavor only) toothpaste for children.

A few years ago, a teenager presented to Dr. Katta with intense bullae on the dorsum of the foot after wearing shoes without socks. “She was wearing white canvas Keds, which looked very innocuous,” she said. Patch testing revealed that the teen reacted to four different rubber accelerators. “When we contacted the company, they [acknowledged] using rubber cement to make the canvas Keds,” Dr. Katta said. “Rubber cement is an adhesive and it does contain rubber accelerators. Later, I saw two cases of children who had walked around all day at the amusement park wearing their Sperry Topsiders without any socks. We couldn’t get any information from that manufacturer, but I suspect that they also use a rubber-based glue to make those shoes.” She characterized shoes as “a real setup for a foot allergy because you have friction, sweat that’s pulling allergen out of an object, and sweat is carrying it over, especially to the dorsum of the foot.”


Dr. Katta has also noticed an uptick in the number of young patients who develop allergic reactions to dyes used to make workout clothing. “If you ever see rashes that do not involve the axillary vault but do have peraxillary accentuation, think textile allergy,” she said. “We’re seeing a lot of reactions to disperse blue clothing dyes. When you think about textile allergy from the dyes, it tends to be the blue and black clothing. It’s more likely in the setting of synthetic fabrics because they leach out dyes more easily, and it’s more likely in the setting of sweat because sweat helps pull allergen out. I’m seeing it a lot from sports uniforms and tight black leggings and tight sports bras that people are wearing. I’m also seeing some from bathing suits and swim shirts.”

Exposure to products containing the preservative methylisothiazolinone (MI) is also on the rise. It ranks as the second most frequent allergen for which the North American Contact Dermatitis Group is seeing positive results on patch testing, with rates of 13.4%. MI can be found in many skin care products and “probably about half of school glues, fabric glues, and craft glues,” Dr. Katta said. “Stick versus liquid doesn’t make a difference.” Children and teens often use craft glues, laundry detergents, and other products to create “slime” as a way to learn about viscosity, polymers, and chemical reactions. “Sometimes these children have sensitive skin, or they’re using it with prolonged contact, so they may be sensitizing themselves to the MI,” she said.

She concluded her remarks by noting that an increasing number of young patients are developing reactions to wearable medical devices such as insulin pumps and glucose monitors. “With this, the first thing to think about is frictional irritant dermatitis,” she said. “You can put Scanpor medical paper tape on people’s back for 48 hours straight to patch test them. Some people are incredibly reactive to the friction of just that tape. You also have to think about trapped allergen. One of my patients reacted to colophony, fragrance mix, and propylene glycol, all of which were contained in his skin care products. Some people are getting advice from other patients to use Mastisol liquid adhesive to help their glucose monitors stick better. Mastisol has a high rate of cross-reactivity with balsam of Peru, so it’s a fragrance allergen. That’s the first thing you want to ask patients about: what products they’re using.”

One of her patients thought she was reacting to adhesive tape on her skin, but in fact she was reacting to two different acrylates: ethylene glycol dimethacrylate (EGDMA) and hydroxyethyl methacrylate (HEMA). “I know about these allergens because I see reactions from butterfly needles in dialysis patients,” Dr. Katta explained. “What happens is, these acrylates are glues or plastics used somewhere else on the device, and they can migrate through barriers.”

In one published case, a 9-year-old boy developed a reaction to ethyl cyanoacrylate contained in a glucose sensor adhesive (Dermatitis. 2017; 28[4]:289-91). It never touched the boy’s skin directly but was presumed to migrate through that tape. “The bottom line is that acrylates may induce contact dermatitis even through perceived barriers,” she said. “Their use anywhere in medical devices may prove problematic.”

Dr. Katta reported that she is a member of the advisory board for Vichy Laboratories.
 

[email protected]

AUSTIN – Not long ago, Rajani Katta, MD, received a text message from a friend who expressed concern about a rash that developed in the underarm of her teenage daughter.

The culprit turned out to be the lavender essential oil contained in an “all natural” deodorant that her daughter had recently switched to – a storyline that Dr. Katta encounters with increasing frequency in her role as clinical professor of dermatology at the University of Texas Health Science Center at Houston.

“Some people may think that you can’t get an allergic reaction to natural products, but we are seeing many allergic reactions to essential oils,” Dr. Katta said at the annual meeting of the Society for Pediatric Dermatology. “When you talk about a natural allergy, it is more likely to occur if your skin barrier is compromised, so I think that’s why we’re seeing it, especially in young girls in the underarm area. If you shave the underarm, you impair that skin barrier and you’re more likely to develop a reaction to something you’re using over it.”

Her list of recommended deodorants includes Almay Roll-On Antiperspirant & Deodorant, Crystal Body Deodorant Stick, Crystal Roll-On Body Deodorant, Vanicream Deodorant for Sensitive Skin (aluminum-free), Vanicream Antiperspirant/Deodorant, and CertainDri Clinical Strength Roll-On. They are fragrance-free and lack propylene glycol, which is a common allergen.

Increasingly, essential oils are being added to lip balms and toothpastes, said Dr. Katta, who is also author of the 2018 book “Glow: The Dermatologist’s Guide to a Whole Foods Younger Skin Diet.” She recalled one patient who presented with chronic chapped lips. “It doesn’t matter how many lip glosses I try; it just keeps getting worse,” the patient told her. The likely culprit turned out to be ingredients contained in flavored lip balm from EOS. Reports of blistering and cracking of the lips from use of the products prompted a class action lawsuit and a notice to consumers from the Food and Drug Administration.

Another patient presented with cracked lips after switching to an “all natural” toothpaste that was labeled “gluten free.”

“It looked great,” Dr. Katta recalled. “Unfortunately it was not flavoring free. She reacted to multiple essential oils, including tea tree oil, contained in the toothpaste. This is being added to a number of toothpastes, and I think we’re going to see more of these types of reactions.”

Other toothpastes contain balsam of Peru, “which is consistently one of the top allergens in patch test clinics,” she said. “One of the components of balsam of Peru is a cinnamon compound, which can be an issue.”

Dr. Katta advises her patients to use Vaseline petroleum jelly as a lip balm and recommends Tom’s of Maine Silly Strawberry Flavor (this flavor only) toothpaste for children.

A few years ago, a teenager presented to Dr. Katta with intense bullae on the dorsum of the foot after wearing shoes without socks. “She was wearing white canvas Keds, which looked very innocuous,” she said. Patch testing revealed that the teen reacted to four different rubber accelerators. “When we contacted the company, they [acknowledged] using rubber cement to make the canvas Keds,” Dr. Katta said. “Rubber cement is an adhesive and it does contain rubber accelerators. Later, I saw two cases of children who had walked around all day at the amusement park wearing their Sperry Topsiders without any socks. We couldn’t get any information from that manufacturer, but I suspect that they also use a rubber-based glue to make those shoes.” She characterized shoes as “a real setup for a foot allergy because you have friction, sweat that’s pulling allergen out of an object, and sweat is carrying it over, especially to the dorsum of the foot.”


Dr. Katta has also noticed an uptick in the number of young patients who develop allergic reactions to dyes used to make workout clothing. “If you ever see rashes that do not involve the axillary vault but do have peraxillary accentuation, think textile allergy,” she said. “We’re seeing a lot of reactions to disperse blue clothing dyes. When you think about textile allergy from the dyes, it tends to be the blue and black clothing. It’s more likely in the setting of synthetic fabrics because they leach out dyes more easily, and it’s more likely in the setting of sweat because sweat helps pull allergen out. I’m seeing it a lot from sports uniforms and tight black leggings and tight sports bras that people are wearing. I’m also seeing some from bathing suits and swim shirts.”

Exposure to products containing the preservative methylisothiazolinone (MI) is also on the rise. It ranks as the second most frequent allergen for which the North American Contact Dermatitis Group is seeing positive results on patch testing, with rates of 13.4%. MI can be found in many skin care products and “probably about half of school glues, fabric glues, and craft glues,” Dr. Katta said. “Stick versus liquid doesn’t make a difference.” Children and teens often use craft glues, laundry detergents, and other products to create “slime” as a way to learn about viscosity, polymers, and chemical reactions. “Sometimes these children have sensitive skin, or they’re using it with prolonged contact, so they may be sensitizing themselves to the MI,” she said.

She concluded her remarks by noting that an increasing number of young patients are developing reactions to wearable medical devices such as insulin pumps and glucose monitors. “With this, the first thing to think about is frictional irritant dermatitis,” she said. “You can put Scanpor medical paper tape on people’s back for 48 hours straight to patch test them. Some people are incredibly reactive to the friction of just that tape. You also have to think about trapped allergen. One of my patients reacted to colophony, fragrance mix, and propylene glycol, all of which were contained in his skin care products. Some people are getting advice from other patients to use Mastisol liquid adhesive to help their glucose monitors stick better. Mastisol has a high rate of cross-reactivity with balsam of Peru, so it’s a fragrance allergen. That’s the first thing you want to ask patients about: what products they’re using.”

One of her patients thought she was reacting to adhesive tape on her skin, but in fact she was reacting to two different acrylates: ethylene glycol dimethacrylate (EGDMA) and hydroxyethyl methacrylate (HEMA). “I know about these allergens because I see reactions from butterfly needles in dialysis patients,” Dr. Katta explained. “What happens is, these acrylates are glues or plastics used somewhere else on the device, and they can migrate through barriers.”

In one published case, a 9-year-old boy developed a reaction to ethyl cyanoacrylate contained in a glucose sensor adhesive (Dermatitis. 2017; 28[4]:289-91). It never touched the boy’s skin directly but was presumed to migrate through that tape. “The bottom line is that acrylates may induce contact dermatitis even through perceived barriers,” she said. “Their use anywhere in medical devices may prove problematic.”

Dr. Katta reported that she is a member of the advisory board for Vichy Laboratories.
 

[email protected]

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.