T he thin-layer rapid use epicutaneous (T.R.U.E.) Test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where a specific allergen is derived or what products should be avoided by patients. With this in mind, this column was developed to provide educational information about the T.R.U.E. Test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight appropriate products patients should avoid when they are allergic to a specific allergen. Contact Dermatides Allergic contact dermatitis is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-occupational based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis, the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this column, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration We present a case in point. Recently, a patient presented to the University of Miami Allergic Contact Dermatitis Clinic having had itching, burning and blistering of her scalp after a salon session that involved having her hair colored, washed and set. Her main concern was to be able to dye her hair again and remove the stigmata of graying roots. The History of Paraphenylenediamine During a hairdressing session, patients are potentially sensitized to many active and inactive ingredients from ammonia to peroxide, but paraphenylenediamine (PPD) is by far the most common and, therefore, the most suspect. PPD is an oxidative chemical substance that is widely used as a permanent hair dye. The first documented cases of PPD allergy in hairdressers date back to the late 19th century.3 It has been suggested that Oscar Wilde (1856-1900) suffered from contact dermatitis due to PPD-based hair dye. Near the end of his life, Wilde suffered from a suppurating otitis media and an unidentified pruritic skin disease affecting his face, arms, chest, and back. It is hypothesized that Wilde sensitized himself to PPD by using a dye on his graying hair and subsequently developed an allergic contact dermatitis.4 PPD made its way into the mass market through the work of Eugene Schueller, a young French chemist who began manufacturing hair dye in his Paris apartment in 1907. Since it was “safe,” he then sold it to Parisian hairdressers. His main chemical ingredient was called paraphenylenediamine, and his new permanent hair dye was dubbed “Aureole” for “radiance around the head.” In 1909 Schueller registered his company as Societe Francaise de Teintures Inoffensives pour Cheveux, which ironically, means French Harmless Hair Dye Company. The Nature of the “Inoffensiveness” of the hair cream remains somewhat tongue-in-cheek, as this eccentric scientist was well known to taste hair creams to ensure that their chemical composition was correct. Eventually, the company name was changed to L’Oreal just because Schueller liked how it sounded.5,6 Currently, the L’Oreal corporation maintains a vast presence worldwide (with its subsidiaries Warner communications, Lancôme, Maybelline, Feria, Biolage & Opticurl), and its cleansing, beauty and hair products stock shelves around the globe. This cosmetic giant, which owes its existence to Schueller’s experimentation with PPD in his apartment, now funds the L’Oreal Institute for Ethnic Hair and Skin Research.7 Today, more than 50% of women use permanent or temporary hair dyes for some period of time. Hair dyeing is also increasingly popular among men. Although PPD is used in hair dyes, the FDA prohibits its use on skin.8 In spite of this, many temporary tattoo artists mix PPD with “natural” henna to give it a brown-black color and to accelerate the fixing time of a temporary henna tattoo.9 This can result in severe dermatitis and long lasting consequences such as scarring and post-inflammatory pigmentation changes. Patients with a history of dermatitis from henna tattoos should avoid PPD-containing hair dyes. Additionally, the FDA has received reports of allergic reactions to “temporary-water-application-tattoos,” a growing fad in the under 18-year-old population, as parents generally permit this type of tattooing.9 Studies report a possible association between PPD exposure and an increased risk of developing bladder cancer in humans and rats. It is suggested that this may be due to the slower rate of detoxification of PPD, resulting in metabolite formation.10 Additionally, topical application and subcutaneous injection of PPD resulted in an increased incidence of mammary, uterine, urinary, bladder and lung tumors in rats, which may be related to the PPD treatment.11 Conversely, Takkouche et al. recently performed a meta-analysis of 79 studies to assess the relative risk of cancer in hair dye users (occupational exposures were excluded). They determined that the pooled relative risk for “ever” users of hair dyes to be 1.06 (95% CI) for breast cancer, 1.01 (95% CI) for bladder cancer, and 1.15 (95% CI) for hematopoietic cancers. While strong evidence for a marked increase in cancer risk was not found, the authors concluded that further investigations were warranted.12 Still, PPD is a commonly used hair dye because it results in a natural look and provides permanent results. The hair can subsequently undergo perming and shampooing without losing color. A prohapten, PPD is oxidized to the allergenic hapten either in the epidermis or the dermis.13 PPD becomes colored upon oxidation, and it is the intermediate partially oxidized state that causes allergy in sensitive individuals. Reactions include mild dermatitis of the upper eyelids and rims of the ears to severe blistering of the scalp with facial edema (see photo at left).14,15 In very severe cases, the reaction can lead to urticaria and rarely, anaphylaxis. Additionally, sensitization to PPD should be acknowledged as an occupational hazard for hairdressers, cosmetologists, photographic developers, printers and textile and fur dyers. Also important are the cross reactions of PPD with other compounds that also have an amino group in the para position of their benzene ring. (See table 1.) The notoriety of this allergen has earned it a nomination for 2006 allergen of the year. Testing for PPD Sensitivity Patch testing for PPD allergy can be accomplished with the T.R.U.E. Test [site #20]. The T.R.U.E Test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that could be used by general dermatologists everywhere. In cases where the T.R.U.E. Test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,500 members of the American Academy of Dermatology. Patch testing support as well as patient education materials can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of This Patient Case Our patient underscores the importance of appropriate patch testing and subsequent patient education. Through comprehensive patch testing we were able to delineate this patient’s allergies and recommend a safe product alternative. Armed with this powerful knowledge, the patient could prevent further exposures and potentially scarring reactions. On follow-up, this patient beamed, “I have my life back.”
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Focus on T.R.U.E. Test Allergen #20: Paraphenylenediamine
T he thin-layer rapid use epicutaneous (T.R.U.E.) Test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where a specific allergen is derived or what products should be avoided by patients. With this in mind, this column was developed to provide educational information about the T.R.U.E. Test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight appropriate products patients should avoid when they are allergic to a specific allergen. Contact Dermatides Allergic contact dermatitis is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-occupational based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis, the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this column, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration We present a case in point. Recently, a patient presented to the University of Miami Allergic Contact Dermatitis Clinic having had itching, burning and blistering of her scalp after a salon session that involved having her hair colored, washed and set. Her main concern was to be able to dye her hair again and remove the stigmata of graying roots. The History of Paraphenylenediamine During a hairdressing session, patients are potentially sensitized to many active and inactive ingredients from ammonia to peroxide, but paraphenylenediamine (PPD) is by far the most common and, therefore, the most suspect. PPD is an oxidative chemical substance that is widely used as a permanent hair dye. The first documented cases of PPD allergy in hairdressers date back to the late 19th century.3 It has been suggested that Oscar Wilde (1856-1900) suffered from contact dermatitis due to PPD-based hair dye. Near the end of his life, Wilde suffered from a suppurating otitis media and an unidentified pruritic skin disease affecting his face, arms, chest, and back. It is hypothesized that Wilde sensitized himself to PPD by using a dye on his graying hair and subsequently developed an allergic contact dermatitis.4 PPD made its way into the mass market through the work of Eugene Schueller, a young French chemist who began manufacturing hair dye in his Paris apartment in 1907. Since it was “safe,” he then sold it to Parisian hairdressers. His main chemical ingredient was called paraphenylenediamine, and his new permanent hair dye was dubbed “Aureole” for “radiance around the head.” In 1909 Schueller registered his company as Societe Francaise de Teintures Inoffensives pour Cheveux, which ironically, means French Harmless Hair Dye Company. The Nature of the “Inoffensiveness” of the hair cream remains somewhat tongue-in-cheek, as this eccentric scientist was well known to taste hair creams to ensure that their chemical composition was correct. Eventually, the company name was changed to L’Oreal just because Schueller liked how it sounded.5,6 Currently, the L’Oreal corporation maintains a vast presence worldwide (with its subsidiaries Warner communications, Lancôme, Maybelline, Feria, Biolage & Opticurl), and its cleansing, beauty and hair products stock shelves around the globe. This cosmetic giant, which owes its existence to Schueller’s experimentation with PPD in his apartment, now funds the L’Oreal Institute for Ethnic Hair and Skin Research.7 Today, more than 50% of women use permanent or temporary hair dyes for some period of time. Hair dyeing is also increasingly popular among men. Although PPD is used in hair dyes, the FDA prohibits its use on skin.8 In spite of this, many temporary tattoo artists mix PPD with “natural” henna to give it a brown-black color and to accelerate the fixing time of a temporary henna tattoo.9 This can result in severe dermatitis and long lasting consequences such as scarring and post-inflammatory pigmentation changes. Patients with a history of dermatitis from henna tattoos should avoid PPD-containing hair dyes. Additionally, the FDA has received reports of allergic reactions to “temporary-water-application-tattoos,” a growing fad in the under 18-year-old population, as parents generally permit this type of tattooing.9 Studies report a possible association between PPD exposure and an increased risk of developing bladder cancer in humans and rats. It is suggested that this may be due to the slower rate of detoxification of PPD, resulting in metabolite formation.10 Additionally, topical application and subcutaneous injection of PPD resulted in an increased incidence of mammary, uterine, urinary, bladder and lung tumors in rats, which may be related to the PPD treatment.11 Conversely, Takkouche et al. recently performed a meta-analysis of 79 studies to assess the relative risk of cancer in hair dye users (occupational exposures were excluded). They determined that the pooled relative risk for “ever” users of hair dyes to be 1.06 (95% CI) for breast cancer, 1.01 (95% CI) for bladder cancer, and 1.15 (95% CI) for hematopoietic cancers. While strong evidence for a marked increase in cancer risk was not found, the authors concluded that further investigations were warranted.12 Still, PPD is a commonly used hair dye because it results in a natural look and provides permanent results. The hair can subsequently undergo perming and shampooing without losing color. A prohapten, PPD is oxidized to the allergenic hapten either in the epidermis or the dermis.13 PPD becomes colored upon oxidation, and it is the intermediate partially oxidized state that causes allergy in sensitive individuals. Reactions include mild dermatitis of the upper eyelids and rims of the ears to severe blistering of the scalp with facial edema (see photo at left).14,15 In very severe cases, the reaction can lead to urticaria and rarely, anaphylaxis. Additionally, sensitization to PPD should be acknowledged as an occupational hazard for hairdressers, cosmetologists, photographic developers, printers and textile and fur dyers. Also important are the cross reactions of PPD with other compounds that also have an amino group in the para position of their benzene ring. (See table 1.) The notoriety of this allergen has earned it a nomination for 2006 allergen of the year. Testing for PPD Sensitivity Patch testing for PPD allergy can be accomplished with the T.R.U.E. Test [site #20]. The T.R.U.E Test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that could be used by general dermatologists everywhere. In cases where the T.R.U.E. Test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,500 members of the American Academy of Dermatology. Patch testing support as well as patient education materials can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of This Patient Case Our patient underscores the importance of appropriate patch testing and subsequent patient education. Through comprehensive patch testing we were able to delineate this patient’s allergies and recommend a safe product alternative. Armed with this powerful knowledge, the patient could prevent further exposures and potentially scarring reactions. On follow-up, this patient beamed, “I have my life back.”
T he thin-layer rapid use epicutaneous (T.R.U.E.) Test of 23 common allergens is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where a specific allergen is derived or what products should be avoided by patients. With this in mind, this column was developed to provide educational information about the T.R.U.E. Test allergens. A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight appropriate products patients should avoid when they are allergic to a specific allergen. Contact Dermatides Allergic contact dermatitis is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-occupational based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis, the foremost example of this would be latex hypersensitivity. Although this is beyond the scope of this column, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 The primary focus of this section is to highlight the educational component of allergic contact dermatitis. Clinical Illustration We present a case in point. Recently, a patient presented to the University of Miami Allergic Contact Dermatitis Clinic having had itching, burning and blistering of her scalp after a salon session that involved having her hair colored, washed and set. Her main concern was to be able to dye her hair again and remove the stigmata of graying roots. The History of Paraphenylenediamine During a hairdressing session, patients are potentially sensitized to many active and inactive ingredients from ammonia to peroxide, but paraphenylenediamine (PPD) is by far the most common and, therefore, the most suspect. PPD is an oxidative chemical substance that is widely used as a permanent hair dye. The first documented cases of PPD allergy in hairdressers date back to the late 19th century.3 It has been suggested that Oscar Wilde (1856-1900) suffered from contact dermatitis due to PPD-based hair dye. Near the end of his life, Wilde suffered from a suppurating otitis media and an unidentified pruritic skin disease affecting his face, arms, chest, and back. It is hypothesized that Wilde sensitized himself to PPD by using a dye on his graying hair and subsequently developed an allergic contact dermatitis.4 PPD made its way into the mass market through the work of Eugene Schueller, a young French chemist who began manufacturing hair dye in his Paris apartment in 1907. Since it was “safe,” he then sold it to Parisian hairdressers. His main chemical ingredient was called paraphenylenediamine, and his new permanent hair dye was dubbed “Aureole” for “radiance around the head.” In 1909 Schueller registered his company as Societe Francaise de Teintures Inoffensives pour Cheveux, which ironically, means French Harmless Hair Dye Company. The Nature of the “Inoffensiveness” of the hair cream remains somewhat tongue-in-cheek, as this eccentric scientist was well known to taste hair creams to ensure that their chemical composition was correct. Eventually, the company name was changed to L’Oreal just because Schueller liked how it sounded.5,6 Currently, the L’Oreal corporation maintains a vast presence worldwide (with its subsidiaries Warner communications, Lancôme, Maybelline, Feria, Biolage & Opticurl), and its cleansing, beauty and hair products stock shelves around the globe. This cosmetic giant, which owes its existence to Schueller’s experimentation with PPD in his apartment, now funds the L’Oreal Institute for Ethnic Hair and Skin Research.7 Today, more than 50% of women use permanent or temporary hair dyes for some period of time. Hair dyeing is also increasingly popular among men. Although PPD is used in hair dyes, the FDA prohibits its use on skin.8 In spite of this, many temporary tattoo artists mix PPD with “natural” henna to give it a brown-black color and to accelerate the fixing time of a temporary henna tattoo.9 This can result in severe dermatitis and long lasting consequences such as scarring and post-inflammatory pigmentation changes. Patients with a history of dermatitis from henna tattoos should avoid PPD-containing hair dyes. Additionally, the FDA has received reports of allergic reactions to “temporary-water-application-tattoos,” a growing fad in the under 18-year-old population, as parents generally permit this type of tattooing.9 Studies report a possible association between PPD exposure and an increased risk of developing bladder cancer in humans and rats. It is suggested that this may be due to the slower rate of detoxification of PPD, resulting in metabolite formation.10 Additionally, topical application and subcutaneous injection of PPD resulted in an increased incidence of mammary, uterine, urinary, bladder and lung tumors in rats, which may be related to the PPD treatment.11 Conversely, Takkouche et al. recently performed a meta-analysis of 79 studies to assess the relative risk of cancer in hair dye users (occupational exposures were excluded). They determined that the pooled relative risk for “ever” users of hair dyes to be 1.06 (95% CI) for breast cancer, 1.01 (95% CI) for bladder cancer, and 1.15 (95% CI) for hematopoietic cancers. While strong evidence for a marked increase in cancer risk was not found, the authors concluded that further investigations were warranted.12 Still, PPD is a commonly used hair dye because it results in a natural look and provides permanent results. The hair can subsequently undergo perming and shampooing without losing color. A prohapten, PPD is oxidized to the allergenic hapten either in the epidermis or the dermis.13 PPD becomes colored upon oxidation, and it is the intermediate partially oxidized state that causes allergy in sensitive individuals. Reactions include mild dermatitis of the upper eyelids and rims of the ears to severe blistering of the scalp with facial edema (see photo at left).14,15 In very severe cases, the reaction can lead to urticaria and rarely, anaphylaxis. Additionally, sensitization to PPD should be acknowledged as an occupational hazard for hairdressers, cosmetologists, photographic developers, printers and textile and fur dyers. Also important are the cross reactions of PPD with other compounds that also have an amino group in the para position of their benzene ring. (See table 1.) The notoriety of this allergen has earned it a nomination for 2006 allergen of the year. Testing for PPD Sensitivity Patch testing for PPD allergy can be accomplished with the T.R.U.E. Test [site #20]. The T.R.U.E Test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that could be used by general dermatologists everywhere. In cases where the T.R.U.E. Test is inadequate, the patient should undergo comprehensive patch testing. For now, the availability of comprehensive patch testing is limited, as suggested by the fact that the American Contact Dermatitis Society (ACDS) has roughly 450 members compared to the 14,500 members of the American Academy of Dermatology. Patch testing support as well as patient education materials can be obtained from the ACDS through the newly developed Contact Allergen Replacement Database (C.A.R.D.). The Value of This Patient Case Our patient underscores the importance of appropriate patch testing and subsequent patient education. Through comprehensive patch testing we were able to delineate this patient’s allergies and recommend a safe product alternative. Armed with this powerful knowledge, the patient could prevent further exposures and potentially scarring reactions. On follow-up, this patient beamed, “I have my life back.”
