Contact Dermatitis

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.

To the Editor:

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction against antigens to which the skin’s immune system was previously sensitized. The initial sensitization requires penetration of the antigen through the stratum corneum. Thus, the ability of a particle to cause ACD is related to its molecular structure and size, lipophilicity, and protein-binding affinity, as well as the dose and duration of exposure.¹ Psoriasis typically presents as well-demarcated areas of skin that may be erythematous, indurated, and scaly to variable degrees. Histologically, psoriasis plaques are characterized by epidermal hyperplasia in the presence of a T-cell infiltrate and neutrophilic microabscesses. We report a case of a patient with plaque-type psoriasis who experienced ACD with sparing of exposed psoriatic plaques.

A 45-year-old man with a 5-year history of generalized moderate to severe psoriasis undergoing therapy with ustekinumab 45 mg subcutaneously once every 12 weeks presented to the emergency department with intensely erythematous, pruritic, vesicular lesions on the trunk, arms, and legs within 24 hours of exposure to poison oak while hiking. The patient reported pruritus, pain, and swelling of the affected areas. On physical examination, he was afebrile. Widespread erythematous vesicular lesions were noted on the face, trunk, arms, and legs, sparing the well-demarcated scaly psoriatic plaques on the arms and legs (Figure). The patient was given intravenous fluids and intravenous diphenhydramine. After responding to initial treatment, the patient was discharged with ibuprofen and a tapering dose of oral prednisone from 60 mg 5 times daily, to 40 mg 5 times daily, to 20 mg 5 times daily over 15 days.

Plaque psoriasis is a chronic, immune-mediated, inflammatory disease that presents clinically as erythematous well-demarcated plaques with a micaceous scale. The immunologic environment of psoriasis plaques is characterized by infiltration of CD4⁺ T_H17 cells and elevated levels of IL-17, IL-23, tumor necrosis factor α, and IL-1β, which induce keratinocyte hyperproliferation through a complex mechanism resulting in hyperkeratosis composed of orthokeratosis and parakeratosis, a neutrophilic infiltrate, and Munro microabscesses.⁵

The predominant effector cells and the final effects on keratinocyte survival are divergent in psoriasis and ACD. The possibly antagonistic relationship between these immunologic processes is further supported by epidemiologic studies demonstrating a decreased incidence of ACD in patients with psoriasis.^6,7

Our patient demonstrated a typical ACD reaction in response to exposure to urushiol, the allergen present in poison oak, in areas unaffected by psoriasis plaques. Interestingly, the patient displayed this response even while undergoing therapy with ustekinumab, a fully humanized antibody that binds IL-12 and IL-23 and ultimately downregulates T_H17 cell-mediated release of IL-17 in the treatment of psoriasis. Although IL-17 also has been implicated in ACD, the lack of inhibition of ACD with ustekinumab treatment was previously demonstrated in a small retrospective study, indicating a potentially different source of IL-17 in ACD.⁸

Our patient did not demonstrate a typical ACD response in areas of active psoriasis plaques. This phenomenon was of great interest to us. It is possible that the presence of hyperkeratosis, manifested clinically as scaling, served as a mechanical barrier preventing the diffusion and exposure of cutaneous immune cells to urushiol. On the other hand, it is possible that the immunologic environment of the active psoriasis plaque was altered in such a way that it did not demonstrate the typical response to allergen exposure.

We hypothesize that the lack of a typical ACD response at sites of psoriatic plaques in our patient may be attributed to the intensity and duration of exposure to the allergen. Quaranta et al⁹ reported a typical ACD clinical response and a mixed immunohistologic response to nickel patch testing at sites of active plaques in nickel-sensitized psoriasis patients. Patch testing involves 48 hours of direct contact with an allergen, while our patient experienced an estimated 8 to 10 hours of exposure to the allergen prior to removal via washing. Supporting this line of reasoning, a proportion of patients who are responsive to nickel patch testing do not exhibit clinical symptoms in response to casual nickel exposure.¹⁰ Although a physical barrier effect due to hyperkeratosis may have contributed to the lack of ACD response in sites of psoriasis plaques in our patient, it remains possible that a more limited duration of exposure to the allergen is not sufficient to overcome the native immunologic milieu of the psoriasis plaque and induce the immunologic cascade resulting in ACD. Further research into the potentially antagonistic relationship of psoriasis and ACD should be performed to elucidate the interaction between these two common conditions.

To the Editor:

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction against antigens to which the skin’s immune system was previously sensitized. The initial sensitization requires penetration of the antigen through the stratum corneum. Thus, the ability of a particle to cause ACD is related to its molecular structure and size, lipophilicity, and protein-binding affinity, as well as the dose and duration of exposure.¹ Psoriasis typically presents as well-demarcated areas of skin that may be erythematous, indurated, and scaly to variable degrees. Histologically, psoriasis plaques are characterized by epidermal hyperplasia in the presence of a T-cell infiltrate and neutrophilic microabscesses. We report a case of a patient with plaque-type psoriasis who experienced ACD with sparing of exposed psoriatic plaques.

A 45-year-old man with a 5-year history of generalized moderate to severe psoriasis undergoing therapy with ustekinumab 45 mg subcutaneously once every 12 weeks presented to the emergency department with intensely erythematous, pruritic, vesicular lesions on the trunk, arms, and legs within 24 hours of exposure to poison oak while hiking. The patient reported pruritus, pain, and swelling of the affected areas. On physical examination, he was afebrile. Widespread erythematous vesicular lesions were noted on the face, trunk, arms, and legs, sparing the well-demarcated scaly psoriatic plaques on the arms and legs (Figure). The patient was given intravenous fluids and intravenous diphenhydramine. After responding to initial treatment, the patient was discharged with ibuprofen and a tapering dose of oral prednisone from 60 mg 5 times daily, to 40 mg 5 times daily, to 20 mg 5 times daily over 15 days.

Plaque psoriasis is a chronic, immune-mediated, inflammatory disease that presents clinically as erythematous well-demarcated plaques with a micaceous scale. The immunologic environment of psoriasis plaques is characterized by infiltration of CD4⁺ T_H17 cells and elevated levels of IL-17, IL-23, tumor necrosis factor α, and IL-1β, which induce keratinocyte hyperproliferation through a complex mechanism resulting in hyperkeratosis composed of orthokeratosis and parakeratosis, a neutrophilic infiltrate, and Munro microabscesses.⁵

The predominant effector cells and the final effects on keratinocyte survival are divergent in psoriasis and ACD. The possibly antagonistic relationship between these immunologic processes is further supported by epidemiologic studies demonstrating a decreased incidence of ACD in patients with psoriasis.^6,7

Our patient demonstrated a typical ACD reaction in response to exposure to urushiol, the allergen present in poison oak, in areas unaffected by psoriasis plaques. Interestingly, the patient displayed this response even while undergoing therapy with ustekinumab, a fully humanized antibody that binds IL-12 and IL-23 and ultimately downregulates T_H17 cell-mediated release of IL-17 in the treatment of psoriasis. Although IL-17 also has been implicated in ACD, the lack of inhibition of ACD with ustekinumab treatment was previously demonstrated in a small retrospective study, indicating a potentially different source of IL-17 in ACD.⁸

Our patient did not demonstrate a typical ACD response in areas of active psoriasis plaques. This phenomenon was of great interest to us. It is possible that the presence of hyperkeratosis, manifested clinically as scaling, served as a mechanical barrier preventing the diffusion and exposure of cutaneous immune cells to urushiol. On the other hand, it is possible that the immunologic environment of the active psoriasis plaque was altered in such a way that it did not demonstrate the typical response to allergen exposure.

We hypothesize that the lack of a typical ACD response at sites of psoriatic plaques in our patient may be attributed to the intensity and duration of exposure to the allergen. Quaranta et al⁹ reported a typical ACD clinical response and a mixed immunohistologic response to nickel patch testing at sites of active plaques in nickel-sensitized psoriasis patients. Patch testing involves 48 hours of direct contact with an allergen, while our patient experienced an estimated 8 to 10 hours of exposure to the allergen prior to removal via washing. Supporting this line of reasoning, a proportion of patients who are responsive to nickel patch testing do not exhibit clinical symptoms in response to casual nickel exposure.¹⁰ Although a physical barrier effect due to hyperkeratosis may have contributed to the lack of ACD response in sites of psoriasis plaques in our patient, it remains possible that a more limited duration of exposure to the allergen is not sufficient to overcome the native immunologic milieu of the psoriasis plaque and induce the immunologic cascade resulting in ACD. Further research into the potentially antagonistic relationship of psoriasis and ACD should be performed to elucidate the interaction between these two common conditions.

To the Editor:

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction against antigens to which the skin’s immune system was previously sensitized. The initial sensitization requires penetration of the antigen through the stratum corneum. Thus, the ability of a particle to cause ACD is related to its molecular structure and size, lipophilicity, and protein-binding affinity, as well as the dose and duration of exposure.¹ Psoriasis typically presents as well-demarcated areas of skin that may be erythematous, indurated, and scaly to variable degrees. Histologically, psoriasis plaques are characterized by epidermal hyperplasia in the presence of a T-cell infiltrate and neutrophilic microabscesses. We report a case of a patient with plaque-type psoriasis who experienced ACD with sparing of exposed psoriatic plaques.

A 45-year-old man with a 5-year history of generalized moderate to severe psoriasis undergoing therapy with ustekinumab 45 mg subcutaneously once every 12 weeks presented to the emergency department with intensely erythematous, pruritic, vesicular lesions on the trunk, arms, and legs within 24 hours of exposure to poison oak while hiking. The patient reported pruritus, pain, and swelling of the affected areas. On physical examination, he was afebrile. Widespread erythematous vesicular lesions were noted on the face, trunk, arms, and legs, sparing the well-demarcated scaly psoriatic plaques on the arms and legs (Figure). The patient was given intravenous fluids and intravenous diphenhydramine. After responding to initial treatment, the patient was discharged with ibuprofen and a tapering dose of oral prednisone from 60 mg 5 times daily, to 40 mg 5 times daily, to 20 mg 5 times daily over 15 days.

Plaque psoriasis is a chronic, immune-mediated, inflammatory disease that presents clinically as erythematous well-demarcated plaques with a micaceous scale. The immunologic environment of psoriasis plaques is characterized by infiltration of CD4⁺ T_H17 cells and elevated levels of IL-17, IL-23, tumor necrosis factor α, and IL-1β, which induce keratinocyte hyperproliferation through a complex mechanism resulting in hyperkeratosis composed of orthokeratosis and parakeratosis, a neutrophilic infiltrate, and Munro microabscesses.⁵

The predominant effector cells and the final effects on keratinocyte survival are divergent in psoriasis and ACD. The possibly antagonistic relationship between these immunologic processes is further supported by epidemiologic studies demonstrating a decreased incidence of ACD in patients with psoriasis.^6,7

Our patient demonstrated a typical ACD reaction in response to exposure to urushiol, the allergen present in poison oak, in areas unaffected by psoriasis plaques. Interestingly, the patient displayed this response even while undergoing therapy with ustekinumab, a fully humanized antibody that binds IL-12 and IL-23 and ultimately downregulates T_H17 cell-mediated release of IL-17 in the treatment of psoriasis. Although IL-17 also has been implicated in ACD, the lack of inhibition of ACD with ustekinumab treatment was previously demonstrated in a small retrospective study, indicating a potentially different source of IL-17 in ACD.⁸

Our patient did not demonstrate a typical ACD response in areas of active psoriasis plaques. This phenomenon was of great interest to us. It is possible that the presence of hyperkeratosis, manifested clinically as scaling, served as a mechanical barrier preventing the diffusion and exposure of cutaneous immune cells to urushiol. On the other hand, it is possible that the immunologic environment of the active psoriasis plaque was altered in such a way that it did not demonstrate the typical response to allergen exposure.

We hypothesize that the lack of a typical ACD response at sites of psoriatic plaques in our patient may be attributed to the intensity and duration of exposure to the allergen. Quaranta et al⁹ reported a typical ACD clinical response and a mixed immunohistologic response to nickel patch testing at sites of active plaques in nickel-sensitized psoriasis patients. Patch testing involves 48 hours of direct contact with an allergen, while our patient experienced an estimated 8 to 10 hours of exposure to the allergen prior to removal via washing. Supporting this line of reasoning, a proportion of patients who are responsive to nickel patch testing do not exhibit clinical symptoms in response to casual nickel exposure.¹⁰ Although a physical barrier effect due to hyperkeratosis may have contributed to the lack of ACD response in sites of psoriasis plaques in our patient, it remains possible that a more limited duration of exposure to the allergen is not sufficient to overcome the native immunologic milieu of the psoriasis plaque and induce the immunologic cascade resulting in ACD. Further research into the potentially antagonistic relationship of psoriasis and ACD should be performed to elucidate the interaction between these two common conditions.

Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.

The differential diagnosis of dermatoses overlying pacemakers includes infection, irritant or allergic contact dermatitis, reticular telangiectatic erythema (caused by local venous obstruction and pressure dermatitis), and impending skin erosion/device extrusion.

Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.

After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.

Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.

Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.

Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.

This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.

The differential diagnosis of dermatoses overlying pacemakers includes infection, irritant or allergic contact dermatitis, reticular telangiectatic erythema (caused by local venous obstruction and pressure dermatitis), and impending skin erosion/device extrusion.

Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.

After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.

Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.

Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.

Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.

This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.

The differential diagnosis of dermatoses overlying pacemakers includes infection, irritant or allergic contact dermatitis, reticular telangiectatic erythema (caused by local venous obstruction and pressure dermatitis), and impending skin erosion/device extrusion.

Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.

After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.

Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.

Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.

Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.

This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Heparin is a naturally occurring anticoagulant and is commonly used to treat or prevent venous thrombosis or the extension of thrombosis.¹ Heparin is composed of 15-kDa chains of complex polysaccharides with repeating pentasaccharide sequences. These high-affinity pentasaccharide subunits bind and activate antithrombin III, which exerts its dominant anticoagulant effects through the inhibition of factor Xa.²

Adverse effects of heparin administration include bleeding, injection-site pain, and thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is a serious side effect wherein antibodies are formed against platelet antigens and predispose the patient to venous and arterial thrombosis.³ Dermatologic adverse effects of heparin range from commonly reported injection-site eruptions to the more rarely described distant or generalized cutaneous reactions.⁴

Bullous hemorrhagic dermatosis is a poorly understood idiosyncratic drug reaction characterized by tense, blood-filled blisters that arise following the administration of subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin (UFH). First reported in 2006 by Perrinaud et al,⁵ only a few case reports describing this phenomenon exist in the literature.^6-8 We report a unique case of hemorrhagic bullae limited to the oral mucosa.

Case Report

An 84-year-old man was admitted to the cardiology service with severe substernal chest pain. An electrocardiogram did not show any ST-segment elevations; however, he had elevated troponin T levels. He had a medical history of coronary artery disease complicated by myocardial infarction (MI), as well as ischemic cardiomyopathy, hypertension, hyperlipidemia, ischemic stroke, and pulmonary embolism for which he was on long-term anticoagulation for years with warfarin, aspirin, and clopidogrel. The patient was diagnosed with a non–ST-segment elevation MI. Accordingly, the patient’s warfarin was discontinued, and he was administered a bolus and continuous infusion of UFH. He also was continued on aspirin and clopidogrel. Within 6 hours of initiation of UFH, the patient noted multiple discrete swollen lesions in the mouth. Dermatology consultation and biopsy of the lesions were deferred due to acute management of the patient’s MI.

Physical examination revealed a moist oral mucosa with 7 slightly raised, hemorrhagic bullae ranging from 2 to 7 mm in diameter (Figure, A and B). One oral lesion was tense and had become denuded prior to evaluation. Laboratory testing included a normal platelet count (160,000/µL), a nearly therapeutic international normalized ratio (1.9), and a partial thromboplastin time that was initially normal (27 seconds) prior to admission and development of the oral lesions but found to be elevated (176 seconds) after admission and initial UFH bolus.

Comment

Heparin-Induced Skin Lesions
The 2 most common types of heparin-induced skin lesions are delayed-type hypersensitivity reactions and immune-mediated HIT. A 2009 Canadian study found that the overwhelming majority of heparin-induced skin lesions are due to delayed-type hypersensitivity reactions.⁴ The majority of these reactions occurred at or near the injection site on the abdomen and presented as eczematous plaques. Distant cutaneous involvement and lesions of the buccal mucosa were not as commonly reported. Female sex, obesity, and heparin treatment exceeding 9 days were identified as risk factors in the development of delayed-type hypersensitivity reactions, but our patient did not have any of these risk factors.⁴

Types of HIT
Heparin-induced thrombocytopenia is one of the most serious adverse reactions to heparin administration. There are 2 subtypes of HIT, which differ in their clinical significance and pathophysiology.⁹ Type I HIT is a non–immune-mediated reaction that results from the direct effect of heparin on platelets, which causes platelet aggregation and thrombocytopenia. It presents within the first 2 days after heparin exposure.

Type II HIT is an immune-mediated response caused by the formation of IgG autoantibodies against the heparin–platelet factor 4 complex. Antibody formation and thrombocytopenia typically occur after 4 to 10 days of heparin exposure, and there can be devastating arterial and venous thrombotic complications.

Diagnosis of HIT
Heparin-induced thrombocytopenia should be suspected in patients with a lowered platelet count, particularly if the decrease is more than 50% from baseline, and in patients who develop stroke, MI, pulmonary embolism, or deep vein thrombosis while on heparin. Heparin-induced thrombocytopenia was not observed in our patient, as his platelet count remained stable between 160,000 and 164,000/µL throughout his hospital stay and he did not develop any evidence of thrombosis.

Differential Diagnosis
Our patient’s lesions appeared morphologically similar to angina bullosa haemorrhagica, but this condition was less likely based on other clinical features. Typically, angina bullosa haemorrhagica appears as a solitary, blood-filled blister due to oral mucosal trauma from the ingestion of hard or abrasive food.¹⁰ Angina bullosa haemorrhagica most often is located on the soft palate because of its susceptibility to injury during mastication, and this lesion tends to be painful.¹¹ In contrast, our patient developed 7 painless lesions on the buccal mucosa, sparing the soft palate, and without any history of preceding trauma.

Bullous pemphigoid also was considered given the presence of tense bullae in an elderly patient. However, the rapid and spontaneous resolution of these lesions with complete lack of skin involvement made this diagnosis less likely.¹²

Heparin-Induced Bullous Hemorrhagic Dermatosis
Because our patient described a similar reaction while taking enoxaparin in the past, this case represents an idiosyncratic drug reaction, possibly from antibodies to a heparin-antigen complex. Heparin-induced bullous hemorrhagic dermatosis is a rarely reported condition with the majority of lesions presenting on the extremities.

Conclusion

We describe a rare side effect of heparin therapy characterized by discrete blisters on the oral mucosa. However, familiarity with the spectrum of reactions to heparin allowed the patient to continue heparin therapy despite this side effect, as the eruption was not life-threatening and the benefit of continuing heparin outweighed this adverse effect.

Heparin is a naturally occurring anticoagulant and is commonly used to treat or prevent venous thrombosis or the extension of thrombosis.¹ Heparin is composed of 15-kDa chains of complex polysaccharides with repeating pentasaccharide sequences. These high-affinity pentasaccharide subunits bind and activate antithrombin III, which exerts its dominant anticoagulant effects through the inhibition of factor Xa.²

Adverse effects of heparin administration include bleeding, injection-site pain, and thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is a serious side effect wherein antibodies are formed against platelet antigens and predispose the patient to venous and arterial thrombosis.³ Dermatologic adverse effects of heparin range from commonly reported injection-site eruptions to the more rarely described distant or generalized cutaneous reactions.⁴

Bullous hemorrhagic dermatosis is a poorly understood idiosyncratic drug reaction characterized by tense, blood-filled blisters that arise following the administration of subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin (UFH). First reported in 2006 by Perrinaud et al,⁵ only a few case reports describing this phenomenon exist in the literature.^6-8 We report a unique case of hemorrhagic bullae limited to the oral mucosa.

Case Report

An 84-year-old man was admitted to the cardiology service with severe substernal chest pain. An electrocardiogram did not show any ST-segment elevations; however, he had elevated troponin T levels. He had a medical history of coronary artery disease complicated by myocardial infarction (MI), as well as ischemic cardiomyopathy, hypertension, hyperlipidemia, ischemic stroke, and pulmonary embolism for which he was on long-term anticoagulation for years with warfarin, aspirin, and clopidogrel. The patient was diagnosed with a non–ST-segment elevation MI. Accordingly, the patient’s warfarin was discontinued, and he was administered a bolus and continuous infusion of UFH. He also was continued on aspirin and clopidogrel. Within 6 hours of initiation of UFH, the patient noted multiple discrete swollen lesions in the mouth. Dermatology consultation and biopsy of the lesions were deferred due to acute management of the patient’s MI.

Physical examination revealed a moist oral mucosa with 7 slightly raised, hemorrhagic bullae ranging from 2 to 7 mm in diameter (Figure, A and B). One oral lesion was tense and had become denuded prior to evaluation. Laboratory testing included a normal platelet count (160,000/µL), a nearly therapeutic international normalized ratio (1.9), and a partial thromboplastin time that was initially normal (27 seconds) prior to admission and development of the oral lesions but found to be elevated (176 seconds) after admission and initial UFH bolus.

Comment

Heparin-Induced Skin Lesions
The 2 most common types of heparin-induced skin lesions are delayed-type hypersensitivity reactions and immune-mediated HIT. A 2009 Canadian study found that the overwhelming majority of heparin-induced skin lesions are due to delayed-type hypersensitivity reactions.⁴ The majority of these reactions occurred at or near the injection site on the abdomen and presented as eczematous plaques. Distant cutaneous involvement and lesions of the buccal mucosa were not as commonly reported. Female sex, obesity, and heparin treatment exceeding 9 days were identified as risk factors in the development of delayed-type hypersensitivity reactions, but our patient did not have any of these risk factors.⁴

Types of HIT
Heparin-induced thrombocytopenia is one of the most serious adverse reactions to heparin administration. There are 2 subtypes of HIT, which differ in their clinical significance and pathophysiology.⁹ Type I HIT is a non–immune-mediated reaction that results from the direct effect of heparin on platelets, which causes platelet aggregation and thrombocytopenia. It presents within the first 2 days after heparin exposure.

Type II HIT is an immune-mediated response caused by the formation of IgG autoantibodies against the heparin–platelet factor 4 complex. Antibody formation and thrombocytopenia typically occur after 4 to 10 days of heparin exposure, and there can be devastating arterial and venous thrombotic complications.

Diagnosis of HIT
Heparin-induced thrombocytopenia should be suspected in patients with a lowered platelet count, particularly if the decrease is more than 50% from baseline, and in patients who develop stroke, MI, pulmonary embolism, or deep vein thrombosis while on heparin. Heparin-induced thrombocytopenia was not observed in our patient, as his platelet count remained stable between 160,000 and 164,000/µL throughout his hospital stay and he did not develop any evidence of thrombosis.

Differential Diagnosis
Our patient’s lesions appeared morphologically similar to angina bullosa haemorrhagica, but this condition was less likely based on other clinical features. Typically, angina bullosa haemorrhagica appears as a solitary, blood-filled blister due to oral mucosal trauma from the ingestion of hard or abrasive food.¹⁰ Angina bullosa haemorrhagica most often is located on the soft palate because of its susceptibility to injury during mastication, and this lesion tends to be painful.¹¹ In contrast, our patient developed 7 painless lesions on the buccal mucosa, sparing the soft palate, and without any history of preceding trauma.

Bullous pemphigoid also was considered given the presence of tense bullae in an elderly patient. However, the rapid and spontaneous resolution of these lesions with complete lack of skin involvement made this diagnosis less likely.¹²

Heparin-Induced Bullous Hemorrhagic Dermatosis
Because our patient described a similar reaction while taking enoxaparin in the past, this case represents an idiosyncratic drug reaction, possibly from antibodies to a heparin-antigen complex. Heparin-induced bullous hemorrhagic dermatosis is a rarely reported condition with the majority of lesions presenting on the extremities.

Conclusion

We describe a rare side effect of heparin therapy characterized by discrete blisters on the oral mucosa. However, familiarity with the spectrum of reactions to heparin allowed the patient to continue heparin therapy despite this side effect, as the eruption was not life-threatening and the benefit of continuing heparin outweighed this adverse effect.

Heparin is a naturally occurring anticoagulant and is commonly used to treat or prevent venous thrombosis or the extension of thrombosis.¹ Heparin is composed of 15-kDa chains of complex polysaccharides with repeating pentasaccharide sequences. These high-affinity pentasaccharide subunits bind and activate antithrombin III, which exerts its dominant anticoagulant effects through the inhibition of factor Xa.²

Adverse effects of heparin administration include bleeding, injection-site pain, and thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is a serious side effect wherein antibodies are formed against platelet antigens and predispose the patient to venous and arterial thrombosis.³ Dermatologic adverse effects of heparin range from commonly reported injection-site eruptions to the more rarely described distant or generalized cutaneous reactions.⁴

Bullous hemorrhagic dermatosis is a poorly understood idiosyncratic drug reaction characterized by tense, blood-filled blisters that arise following the administration of subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin (UFH). First reported in 2006 by Perrinaud et al,⁵ only a few case reports describing this phenomenon exist in the literature.^6-8 We report a unique case of hemorrhagic bullae limited to the oral mucosa.

Case Report

An 84-year-old man was admitted to the cardiology service with severe substernal chest pain. An electrocardiogram did not show any ST-segment elevations; however, he had elevated troponin T levels. He had a medical history of coronary artery disease complicated by myocardial infarction (MI), as well as ischemic cardiomyopathy, hypertension, hyperlipidemia, ischemic stroke, and pulmonary embolism for which he was on long-term anticoagulation for years with warfarin, aspirin, and clopidogrel. The patient was diagnosed with a non–ST-segment elevation MI. Accordingly, the patient’s warfarin was discontinued, and he was administered a bolus and continuous infusion of UFH. He also was continued on aspirin and clopidogrel. Within 6 hours of initiation of UFH, the patient noted multiple discrete swollen lesions in the mouth. Dermatology consultation and biopsy of the lesions were deferred due to acute management of the patient’s MI.

Physical examination revealed a moist oral mucosa with 7 slightly raised, hemorrhagic bullae ranging from 2 to 7 mm in diameter (Figure, A and B). One oral lesion was tense and had become denuded prior to evaluation. Laboratory testing included a normal platelet count (160,000/µL), a nearly therapeutic international normalized ratio (1.9), and a partial thromboplastin time that was initially normal (27 seconds) prior to admission and development of the oral lesions but found to be elevated (176 seconds) after admission and initial UFH bolus.

Comment

Heparin-Induced Skin Lesions
The 2 most common types of heparin-induced skin lesions are delayed-type hypersensitivity reactions and immune-mediated HIT. A 2009 Canadian study found that the overwhelming majority of heparin-induced skin lesions are due to delayed-type hypersensitivity reactions.⁴ The majority of these reactions occurred at or near the injection site on the abdomen and presented as eczematous plaques. Distant cutaneous involvement and lesions of the buccal mucosa were not as commonly reported. Female sex, obesity, and heparin treatment exceeding 9 days were identified as risk factors in the development of delayed-type hypersensitivity reactions, but our patient did not have any of these risk factors.⁴

Types of HIT
Heparin-induced thrombocytopenia is one of the most serious adverse reactions to heparin administration. There are 2 subtypes of HIT, which differ in their clinical significance and pathophysiology.⁹ Type I HIT is a non–immune-mediated reaction that results from the direct effect of heparin on platelets, which causes platelet aggregation and thrombocytopenia. It presents within the first 2 days after heparin exposure.

Type II HIT is an immune-mediated response caused by the formation of IgG autoantibodies against the heparin–platelet factor 4 complex. Antibody formation and thrombocytopenia typically occur after 4 to 10 days of heparin exposure, and there can be devastating arterial and venous thrombotic complications.

Diagnosis of HIT
Heparin-induced thrombocytopenia should be suspected in patients with a lowered platelet count, particularly if the decrease is more than 50% from baseline, and in patients who develop stroke, MI, pulmonary embolism, or deep vein thrombosis while on heparin. Heparin-induced thrombocytopenia was not observed in our patient, as his platelet count remained stable between 160,000 and 164,000/µL throughout his hospital stay and he did not develop any evidence of thrombosis.

Differential Diagnosis
Our patient’s lesions appeared morphologically similar to angina bullosa haemorrhagica, but this condition was less likely based on other clinical features. Typically, angina bullosa haemorrhagica appears as a solitary, blood-filled blister due to oral mucosal trauma from the ingestion of hard or abrasive food.¹⁰ Angina bullosa haemorrhagica most often is located on the soft palate because of its susceptibility to injury during mastication, and this lesion tends to be painful.¹¹ In contrast, our patient developed 7 painless lesions on the buccal mucosa, sparing the soft palate, and without any history of preceding trauma.

Bullous pemphigoid also was considered given the presence of tense bullae in an elderly patient. However, the rapid and spontaneous resolution of these lesions with complete lack of skin involvement made this diagnosis less likely.¹²

Heparin-Induced Bullous Hemorrhagic Dermatosis
Because our patient described a similar reaction while taking enoxaparin in the past, this case represents an idiosyncratic drug reaction, possibly from antibodies to a heparin-antigen complex. Heparin-induced bullous hemorrhagic dermatosis is a rarely reported condition with the majority of lesions presenting on the extremities.

Conclusion

We describe a rare side effect of heparin therapy characterized by discrete blisters on the oral mucosa. However, familiarity with the spectrum of reactions to heparin allowed the patient to continue heparin therapy despite this side effect, as the eruption was not life-threatening and the benefit of continuing heparin outweighed this adverse effect.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

In 2017, consumers spent an average of $8.53 billion on nail services.¹ This booming industry is set to grow to more than $15.5 billion by 2024.² Nail polishes and other nail cosmetic trends can present new exposures for consumers, including chemicals that can elicit allergic contact dermatitis. In this article, we discuss new nail trends and their associated allergens, the acrylates.

Tosylamide/Formaldehyde Resin

Traditionally, the most widely recognized nail polish allergen has been tosylamide/formaldehyde resin (TSFR). However, there now are many touted TSFR-free nail polishes on the market, and the rate of positive reactions to this chemical has been declining in recent years. The North American Contact Dermatitis Group reported a positive reaction rate of 1.3% from 2005 through 2006,³ and rates decreased to 0.9% from 2015 through 2016.⁴ An Australian study demonstrated a similar reduction in positive reaction rates to nail polish chemicals, with only 0.7% of patients reacting to TSFR from 2014 to 2016 and 0% in 2017. It is theorized that this reduction occurred from replacing TSFR in traditional nail polishes with other chemicals such as polyester resins and cellulose acetate butyrate.⁵

Acrylate-Based Nail Treatments

Consumers recently have been gravitating toward acrylate-based nail treatments vs traditional nail polishes for a variety of reasons. Often referred to as gels, dips, or shellac, acrylate-based nail treatments represent a hot new trend in nail cosmetics. These manicures are resistant to chipping and scratches, creating a like-new look that lasts for weeks after application. The long-lasting nature of acrylate-based nail polishes has made them wildly popular with consumers.

Traditional acrylic nails consist of a powder polymer mixed with a liquid monomer, which polymerizes when a catalyst is added.⁶ The procedure is time consuming and can take up to 2 hours for application. In contrast, the newer gel manicure can be completed faster and includes application of acrylate-based nail polish, including a base coat, 2 coats of color, and a top coat. Exposure to either a light-emitting diode (30–60 seconds) or UVA (2 minutes) lamp is necessary after each coat is applied for polymerization (Figure 1).⁶ This long-lasting, semipermanent manicure typically is what patients are referring to when they say they have “gel nails.”

Acrylate Allergy

Patients who are allergic to acrylates can present with different patterns of dermatitis. Although the majority of patients present with dermatitis on the hands, fingers, or wrists, up to 10% may only have facial and neck dermatitis.⁸ Less commonly, the abdomen and thighs can be involved.^6,8 Nail technicians most commonly present with pulpitis with cutaneous fissures.⁸ Other symptoms can include subungual hyperkeratosis, onycholysis, and nail dystrophy. Paresthesia, urticaria, and upper respiratory tract symptoms can occur but are less common.^6,8

Acrylate allergy typically is the result of sensitization to the acrylate monomers. In theory, gel nail acrylate materials are polymerized following exposure to a light-emitting diode or UVA lamp; however, there likely is some incomplete polymerization, which can increase the risk for development of allergy. Allergen exposure can occur due to incorrect application of the light source; inadvertent monomer exposure, which occurs when nail technicians wipe extra acrylate off of a client’s finger(s); or inadvertent application of acrylate monomers to objects in the nail technician’s work environment.^6,8

Several acrylate nail allergens have been reported. Many studies have identified 2-hydroxyethyl methacrylate (HEMA) as the most common nail acrylate allergen.^8,9 At least one study identified 2-hydroxypropyl methacrylate as the most common, with HEMA in second place.⁶ Other reported acrylate allergens have included ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, ethyl cyanoacrylate, 1,4-butanediol diacrylate, hydroxypropyl acrylate, and 2-hydroxyethyl acrylate.^8,9

The American Contact Dermatitis Society Core Allergen Series and the North American Contact Dermatitis Group screening series currently include HEMA, methyl methacrylate, ethyl acrylate, ethyl cyanoacrylate, and TSFR.^4,10 Of note, acrylates are not included in the thin-layer rapid use epicutaneous (T.R.U.E.) patch test (SmartPractice), so they will be missed if this series is used.¹¹ In the setting of suspected nail acrylate allergy, some authors recommend initial screening with HEMA and ethyl cyanoacrylate, with extended acrylate testing if both are negative.⁸

Upon patch testing with an acrylate series, patients frequently react to 2 or more acrylates and the reactions can be strong (++) or extreme (+++), which may represent cosensitization or cross-sensitization.⁸ The likelihood of cross-reactivity between acrylates is not clear, though it has been postulated that it is theoretically possible.⁶

An important pearl for patch testers using the chamber method is proper storage of acrylate allergens and assembly of trays prior to patch testing. Similar to all haptens, manufacturers recommend that acrylates should be stored in a refrigerator, but some authors suggest that acrylates should be stored in the freezer.¹² Acrylates are volatile chemicals and rapidly degrade when exposed to air. A methyl methacrylate preparation loaded into an inert quadrate (IQ) chamber and stored at room temperature showed a nearly undetectable amount of any residual methyl methacrylate 24 hours later. Refrigeration of allergens in chambers slowed but did not stop eventual degradation, with nearly all acrylate preparations reaching an undetectable level of allergen by day 8.¹³ Acrylates, along with other volatile allergens, should only be loaded into chambers immediately prior to placement on the patient.

Allergy Prevention

Prevention of nail acrylate allergy among consumers is simple: avoid contact with the offending allergen. Acrylate spillover (ie, applying the acrylate onto the skin) and direct contact with objects and working surfaces contaminated with acrylate-based nail products should be avoided.⁸ Avoidance is more complicated for nail technicians, but it is thought that nitrile gloves allow for the best dexterity and allergen avoidance when acrylate exposure is brief.¹⁴ Allowable exposure times with nitrile gloves may be 15 to 30 minutes. After this times passes, a glove change is required to avoid exposure.¹⁴ Wearing nitrile gloves for longer than 15 to 30 minutes will result in cutaneous exposure and risk for dermatitis in sensitized patients. If longer wear is desired, one option includes cutting the fingertips off of Silver Shield/4H gloves (Honeywell Safety Products USA, Inc), applying them to the distal fingers, and wearing a standard nitrile glove over top, known as the finger stall technique.⁶ In one study, this technique was recommended to nail technicians with acrylate allergy. A telephone survey conducted 4 to 43 months later confirmed that 36% (8/22) of participants were using the technique without symptoms. In this same study, 73% (16/22) had continued working as nail technicians.⁶

Acrylates are used for other medical purposes, including dental procedures, orthopedic procedures, surgical glues, wound dressings, and contact and intraocular lenses. They also have additional cosmetic applications, including eyelash and hair extensions.⁸ Therefore, it is vital that patients disclose any history of acrylate allergy to both their medical and cosmetic providers.

Our Final Interpretation

Acrylate allergy has become increasingly common, and long-lasting nail treatments often are the culprit. Whether through gels, dips, or shellac, repeated exposure to acrylates through nail treatments can increase the risk for allergy. The T.R.U.E. test alone will not make the diagnosis, as acrylates are not present in this patch test system. It is important to remind your allergic patients that acrylates are present in other compounds used for medical and cosmetic purposes. Avoidance is key, and for allergic patients who love to bedazzle their nails, we suggest less-permanent, acrylate-free nail polishes as alternatives.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

[email protected]

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

[email protected]

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

[email protected]

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

To the Editor:

A 68-year-old white man presented with a firm, gradually enlarging, mildly tender, grayish black papule with central ulceration on the left dorsal wrist of 4 months’ duration (Figure 1). His relevant medical history included multiple basal cell carcinomas (BCCs) and squamous cell carcinomas, as well as a single-lung transplant 2 years prior, for which he was on chronic immunosuppressive therapy with azathioprine, everolimus, tacrolimus, and prednisone. The clinical differential diagnosis included pigmented BCC, malignant melanoma, and ulcerated squamous cell carcinoma.

Histologic examination of the lesion (Figure 2) demonstrated irregular nodules of basaloid tumor cells with rounded nuclei, visible nucleoli, and scant cytoplasm involving the dermis. The tumor produced abrupt matrical-type keratinization, forming ghost cells. The lesion also contained frequent mitotic figures, apoptotic cells, focal areas of necrosis, and abundant melanin pigment. Admixed throughout the lesion were pigmented and dendritic melanocytic cells. The overlying epidermis was focally ulcerated with an adjacent localized connection between the tumor and the epidermis. Keratinocyte atypia was found in the surrounding epidermis, which contained melanophages, solar elastosis, and scattered chronic inflammatory cells. An immunohistochemical study (Figure 3) for tyrosinase demonstrated abundant admixed melanocytic cells. β-Catenin expression was shown in both nuclear and cytoplasmic distributions, and there was focal labeling on BerEP4 staining. Based on these findings, a diagnosis of melanocytic matrical carcinoma (MMC) was made.

Melanocytic matricoma (MM), a rare adnexal tumor, was first described in 1999 by Carlson et al.¹ A PubMed search of articles indexed for MEDLINE using the terms melanocytic and matricoma yielded 24 reported cases in the English-language literature.^1-17 It consists of an admixed population of basaloid matrical and supramatrical cells, ghost cells, and dendritic melanocytes in a well-circumscribed dermal nodule, typically without epidermal or adnexal connection. In comparison to the more commonly described pilomatricoma, which can be uncommonly pigmented, MM typically has only focal areas of ghost cells and lacks cystic architecture.^1,9,10,18 A granulomatous reaction to keratinaceous debris is variably present.^1,9,10 Histologically, the scattered dendritic melanocytes are classically benign, but cases demonstrating melanocyte atypia have been reported.^10,13 Melanocytic matricoma appears most commonly as a black or gray papule on sun-damaged skin in older men and tends not to recur following complete excision; thus, MM is considered to be a clinically benign neoplasm. Given the demographics and distribution of the lesions, exposure to UV radiation is thought to play a contributory role in the pathogenesis.^2,10,19 Melanocytic matricoma is believed to recapitulate the hair follicle in the anagen phase, where there is close interplay between matrical keratinocytes and melanocytes prior to cessation of melanogenesis during the catagen phase.^5,6,8,20,21 Evidence demonstrating highly conserved β-catenin and downstream lymphoid enhancer binding factor 1 (LEF1) expression, as well as pleckstrin homology-like domain, family A, member 1 (PHLDA1) expression (as a marker for follicular stem cells), points to constitutive activity in the Wnt signaling pathway in follicular stem cells of the bulge area as a major agent of tumorigenesis.¹²

Melanocytic matrical carcinoma, also known as malignant MM or matrical carcinoma with melanocytic hyperplasia, may be considered the malignant counterpart to MM.²² A PubMed search of articles indexed for MEDLINE using the terms melanocytic matrical carcinoma, malignant melanocytic matricoma, and matrical carcinoma with melanocytic hyperplasia, with review of references to identify additional citations, yielded 13 reported cases of MMC in the English-language literature (Table).^19,22-30 As with MM, MMC is a biphasic tumor with basaloid matrical and supramatrical cells; focal areas of ghost cells; and admixed, banal-appearing dendritic melanocytes. However, the basaloid component also demonstrates nuclear atypia, mitoses, occasional ulceration, and variably poor circumscription. Clinically these lesions can mimic pigmented BCC, malignant melanoma, or other malignant adnexal tumors.²⁵ Their natural history is unknown due to few reported cases, but they can be correlated with matrical carcinomas, which were first described by Weedon et al³¹ in 1980. A summary of more than 130 cases of matrical carcinomas in the English-language literature found that MMCs have high rates of local recurrence and metastasize in approximately 13% of cases. Wide local excision demonstrated lower rates of recurrence than simple excision (23% vs 83%), but there were insufficient cases to determine the incidence following Mohs micrographic surgery.³² Melanocytic matrical carcinomas also demonstrate mutations in the β-catenin pathway,pointing to a similar pathogenesis as their benign counterparts or perhaps direct malignant transformation.^25,33,34

A subset of MMCs are combined cutaneous tumors (CCTs) consisting of epithelial neoplasms in close association with malignant melanocytes. Two of the more common variants include dermal squamomelanocytic tumors, a term first used by Pool et al,³⁵ and malignant basomelanocytic tumors, as named by Erickson et al,³⁶ but trichoblastomelanomas and other types have been documented.³⁷ Although CCTs typically occur in the same patient populations as MMCs, namely elderly white men with chronically sun-damaged skin,they exhibit several important distinctions.^37-39 By definition, CCTs have a malignant melanocytic component, whereas melanocytes are nonneoplastic in MMCs. The pathogenesis may differ as well. Various mechanisms for the close association of epithelial tumors and melanoma have been proposed, including field cancerization, tumor collision, tumor-tumor metastases, tumor colonization, and others, though CCTs likely arise through combinations of these processes depending upon their subtype.^37-39 Paracrine signaling may play an important role in the pathogenesis of both tumors.^5,6,8,38 As with MMCs, the prognosis of CCTs is limited by relatively few reported cases. Despite advanced Breslow depths in many cases, these tumors display more indolent behavior suggestive of melanoma in situ rather than invasive melanoma, perhaps due to dependence upon epithelial paracrine factors.^37,39-42

Solid-organ transplant recipients have higher rates of more aggressive malignancies, of which skin cancer is the most common.^43-49 Squamous cell carcinoma of the skin accounts for 95% of cutaneous malignancies in this population and occurs at approximately 65 times the rate of the general population.⁵⁰ The risk of other skin cancers also is increased, though less dramatically, including BCC (10-fold increased risk) and melanoma (2- to 8-fold increased risk).^46,50-53 The cause likely is multifactorial, including older age, history of skin cancer pretransplant, more than 5 years posttransplant, male sex, and incrementally as Fitzpatrick skin type decreases from VI to I.^54-56 Immunosuppressive therapy also plays a role in tumorigenesis. Azathioprine metabolites have specifically been implicated in UVA radiation–induced promutagenic oxidative damage to DNA.⁵⁷ Other studies have found no significant differences in the type of immunosuppressant used but instead have correlated rates of skin cancer to overall immunosuppression.^48,55,58 Lung transplant recipients in particular demonstrate high rates of cutaneous malignancy, likely due in part to the necessity of more potent immunosuppressive regimens. Nearly one-third of patients develop a cutaneous malignancy by 5 years and nearly half by 10 years posttransplant.⁵⁵

We report a rare case of MMC in a solid-organ transplant recipient. We hypothesize that the combination of UV radiation exposure–induced photodamage acquired pretransplant in addition to an aggressive immunosuppressive regimen with azathioprine and other agents posttransplant contributed to the development of this patient’s rare malignancy. Although rare, these tumors should remain in the differential diagnosis of clinicians and pathologists caring for this unique patient population.

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

photorobot/Getty Images

“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).

This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.

“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.

The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).

Bruce Jancin/MDedge News

Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.

Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.

“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.


 

When to patch test atopic dermatitis patients

Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.

Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.

“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.

Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
 

How to patch test atopic dermatitis patients

Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.

Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.

“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.

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

[email protected]

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

photorobot/Getty Images

“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).

This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.

“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.

The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).

Bruce Jancin/MDedge News

Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.

Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.

“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.


 

When to patch test atopic dermatitis patients

Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.

Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.

“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.

Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
 

How to patch test atopic dermatitis patients

Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.

Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.

“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.

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

[email protected]

WAIKOLOA, HAWAII – The prevalence of allergic contact dermatitis is elevated among patients with atopic dermatitis – and it pays to know their major sources of risk, according to Jonathan I. Silverberg, MD, PhD.

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“What are atopic dermatitis patients allergic to? It’s all coming from their personal care products and the things being used to treat their atopic dermatitis,” Dr. Silverberg said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Silverberg, of the department of dermatology at Northwestern University, Chicago, coauthored a systematic review and meta-analysis that examined the association between AD and contact sensitization. In their examination of 74 published studies, the investigators found that the likelihood of allergic contact dermatitis was 1.5-fold greater in adults and children with AD than in healthy individuals from the general population (J Am Acad Dermatol. 2017 Jul;77[1]:70-8).

This finding is at odds with an earlier widespread belief that AD patients should not be at increased risk because the immune profile of their primarily Th2-mediated disease would have a suppressant effect on Th1-mediated hypersensitivity.

“Recent data are calling into question old dogmas and reshaping the way we think about this. And this is not just an academic exercise, this is highly clinically relevant,” the dermatologist asserted.

The results of the meta-analysis prompted Dr. Silverberg and colleagues to conduct a retrospective study of more than 500 adults patch tested to an expanded allergen series at Northwestern’s patch test clinic with the purpose of identifying the common offending allergens in patients with AD. The key finding: The patients with AD were significantly more likely to have positive patch test reactions to ingredients in their repetitively used personal care products, topical corticosteroids, and topical antibiotics than the individuals without AD. The probable explanation for this results is that the skin barrier disruption inherent in AD allows for easier passage of weak allergens through the skin (J Am Acad Dermatol. 2018 Dec;79[6]:1028-33.e6).

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Lanolin was identified as a particularly common allergen in the AD group. “Lanolin is found in one of the most commonly used moisturizers we recommend to patients: Aquaphor. It’s also found in tons of lip balms and emollients. Pretty much every soft soap out there contains lanolin, and it’s in a variety of other personal care products,” Dr. Silverberg noted.

Other common offenders in the AD population included fragrance mix II, cinnamal, quaternium-15, budesonide, tixocortol, carba mix, neomycin, bacitracin, rubber mix, and chlorhexidine. Relevance was established in more than 90% of the positive reactions.

“You can patch test them directly to their personal care products and make that connection beautifully and see how they’re reacting to them,” he said.


 

When to patch test atopic dermatitis patients

Dr. Silverberg was a coauthor of multidisciplinary expert consensus guidelines on when to consider patch testing in AD (Dermatitis. 2016 Jul-Aug;27[4]:186-92). “We had to go consensus because we don’t have nearly enough studies to provide true evidence-based recommendations,” he explained.

Because allergic contact dermatitis is a potentially curable comorbid condition in AD patients, it’s important to recognize the scenarios in which patch testing should be considered. These include AD refractory to topical therapy; adolescent- or adult-onset atopic dermatitis; and in AD patients with an atypical or evolving lesional distribution, such as localized dermatitis on the eyelids, head and neck, or hands and feet. Patch testing is also warranted before initiating systemic therapy for AD.

“If you’re about to put a patient on a biologic or phototherapy and step them up to a whole new class of risk of adverse events, that’s an ideal time to think about reversible options,” Dr. Silverberg advised.

Another situation in which he considers patch testing advisable, although this one isn’t covered in the consensus guidelines, is in AD patients with prominent nummular eczema lesions. “Widespread nummular eczema lesions may be a sign of allergic contact dermatitis in atopic dermatitis patients. I’m not saying everyone with nummular lesions is going to have a positive patch test, but it’s definitely a situation you want to think about,” he said.
 

How to patch test atopic dermatitis patients

Most of the common topical allergens in AD patients are not included in the T.R.U.E. Test. An expanded allergen series, such as the American Contact Dermatitis Society core 80 series, is the better way to go.

Once the dermatologist determines that a patient’s positive patch test reaction is relevant, it’s important to recommend the use of personal care products that are “pretty clean,” Dr. Silverberg said.

“Clean in my opinion is not a matter of ‘It should be all organic and all natural,’ ” he emphasized. “I’m not anti- any of that, but clean means having the fewest ingredients possible and trying to steer clear of those really common allergens that patients are highly likely to have been exposed to and potentially sensitized to over the many years of their tenure of atopic dermatitis.”

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to more than a dozen pharmaceutical companies.

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

[email protected]