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To Dye For: PPD and Other Allergenic Ingredients in Hair Dyes P1

Blame it on the Spice Girls: Henna Tattoos and Sensitization to PPD P3

Dear Reader,

This issue focuses on the highly sensitizing allergen, para-phenylenediamine or PPD. It is a common ingredient in hair dyes and the dyes used for temporary tattoos, where its unregulated use threatens to increase the risk of sensitization around the world. We hope these summaries of more in-depth reviews help you explore the causes of contact dermatitis in your own practice.

We support another venue, a CME-accredited annual patch test workshop, intended to improve your expertise with “all things contact dermatitis.” Topics range from patch test basics and hands-on exercises to advanced sessions. We are excited about the third annual workshop, which was held in Phoenix at the end of October. First, the conference was sold out with more than 150 physicians, nurses, and medical students in attendance! Second, the overall ratings of the national and international speakers were excellent, and the comments from attendees speak for themselves: “I am leaving today with so much more knowledge than when I came.” “...this conference proved, of course, there is much more to learn (about patch testing).”

Participants also shared plenty of good advice to help us improve the conference, which we are already busy planning for next year. Whether you are a beginner or an expert, consider joining us next October. Together, we can advance the diagnosis of allergic contact dermatitis.

Kind Regards,

Dr. Curt HamannPresident & CEO, SmartPractice

To Dye For: PPD and Other Allergenic ingredients in Hair Dyes

The blue-black aniline dye, para-phenylenediamine (PPD), is a potent allergen commonly found in permanent and semipermanent hair dyes. As many as

75% (or more) of women and a third of men may dye their hair at some point during their life. The popularity and simplicity of this cosmetic modification ensure that the risk of being sensitized to PPD is relatively high. Not surprisingly, that risk increases for hairdressers among whom PPD is a known and robust occupational allergen. In fact, in North America PPD is one of the top 10 allergens with a prevalence rate of about 5% while in Europe it ranks in the top five (prevalence rate depending on region, 3.5-7%). PPD even finds its way onto the international top 10 list of pediatric allergens with a prevalence that ranges between 2 to 5%. Common symptoms produced by PPD in hair dyes include facial or scalp rashes, facial edema, and hand eczema.

PPD, however, is not the only allergenic ingredient in hair dyes, which may be composed of dozens of chemicals. Recently, a large study of PPD and other ingredients in hair dyes in almost 3000 patients with eczema at 12 centers (11 in Europe and 1 in the United States) was reported. Perhaps not surprisingly, the rate of positive reactions associated with PPD was the highest—4.5%—followed by positive reactions to toluene-2,5-diamine (PTD, 2.8%), p-aminophenol (1.8%), m-aminophenol (1%), and resorcinol (0.1%). Although these four other ingredients are known allergens, they have received far less attention than PPD in the literature. Altogether, the frequency of positive reactions to one or more of these substances was 5.3%.

The concordance between PPD and PTD, p-aminophenol, and m-aminophenol was high, ranging from 80 to 87%. This finding indicates that PPD can effectively screen for allergies to these other chemicals. Nonetheless, testing with only PPD could miss about 13 to 20% of individuals with allergies to these other ingredients. Consequently, the authors argue for testing with a patient’s personnel hair dye product to ensure identification of the underlying allergen.

all things contact dermatitis n e w s & n o t e s

™

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Because many patients may be reluctant to stop dyeing their hair, awareness of specific allergens can help patients choose products free of their particular allergen (Tables 1 and 2). If patients refuse to stop dyeing their hair, they should be cautioned to have their hair dyed in a salon by a professional who may minimize contact between PPD-containing products and their skin by the use of appropriate barriers.

The study also tested 22 other ingredients whose allergenic potential was unknown. There were no positive responses to 11 of these substances. Of the remaining 11 ingredients, rates of positive reactions ranged from 0.1 to 2.2%. p-methylaminophenol, which was associated with the highest rate (2.2%), showed no concordance with PPD. Four substances (4-amino-2-hydroxytol-uene; 2,4-diaminophenoxyethanol HCl; 4-amino-m-cresol; and N, N'-(2-hydroxyethyl)-p-phenylenediamine) exhibited almost complete concordance with PPD. This finding is interesting because only one of these substances is classified in the same chemical cluster (i.e., share similar physicochemical properties) as PPD. The implication is that not all cross reactions depend on structural similarities between compounds.

Of the patients with contact allergies to one of the 5 previously known allergens, 14% were hairdressers, reemphasizing the high risk for these workers, many of whom are eventually forced to abandon their career. Although dyeing hair is the main cause of allergies to PPD, sensitization can also result from exposure to henna, leather and fur, textiles, and some industrial rubber products. Concern that patch testing with 1% PPD in petrolatum can lead to active sensitization has even led the German Contact Dermatitis Group to call for patch testing with 0.35% PPD instead. Based on the size of Finn Chambers and other patch test systems, this smaller dose is similar to the dose of PPD/cm2 currently found in T.R.U.E. TEST, which represents an alternative to patch testing with the allergen in petrolatum. Although the debate over the appropriate dose of PPD may take a while to resolve, the consensus that PPD is an important allergen for patch testing remains.

Table 2. Phenylenediamines and Related Chemicals

Benzenediamine m-benzenediamine

diamino-benzene m-diaminobenzene

diaminobenzene m-fenylendiamin

benzenediamine ethanedioate m-phenylene diamine

phenylene diamine m-phenylenediamine

phenylenediamine meta-aminoaniline

aminoaniline meta-benzenediamine

6PPD meta-diaminobenzene

APCO 2330 metaphenylenediamine

aspartyl-pyridoxal-5'-phosphate p-aminoaniline

C02454 p-benzenediamine

CI developer 11 p-diaminobenzene

developer 11 p-fenylendiamin

developer C p-phenyldiamine

developer H p-phenylene diamine

developer M p-phenylenediamine

direct Brown BR paraphenylen-diamine

direct Brown GG paraphenylenediamine

fenylenodwuamina PLP-ASP

fouramine 1 PPD

m-aminoaniline Renal PF

Table 1. PPD-Free Products for Coloring Hair†

Product Type of Coloring Product Information

Palette by Nature™

(United States)PermanentAvailable in all shades

Free of PPD, PPD derivatives, PTD, amines, ammonia, peroxide, resorcinol, parabens, phthalates, and more

Approved by American Contact Dermatitis Society and Mayo Clinic (CARD) as one of the safes alternatives to conventional hair color for chemically sensitive individuals

Santotint Light(Italian)

PermanentAvailable in blacks, browns, auburns, and blondes

Free of PPD, ammonia, and paraben

John Frieda® Brilliant Color Glaze(United States)

TemporaryAvailable in brunettes

Free of PPD

Contains methylchlorothiazolinone (MCI) and methylisothiazolinone (MI)

Clairol Loving Care®

(United States)Temporary(6-12 shampoos)

No PPD

Do not confuse with Loving Care Cream, which does include PPD

Henna(various countries)

Semi-permanent Must be pure red henna without the addition of PPD

†This partial list is provided as a courtesy and does not constitute product endorsement. Reasonable efforts have been made to provide reliable data, but SmartPractice® cannot assume responsibility for the validity of all materials or for the consequences of their use. Because product ingredients may change, readers are advised to check the product information currently provided by the manufacturer of each product to verify the ingredients before making recommendations to patients. It is the responsibility of the treating physician, relying on experience and knowledge of the patient, to determine the best treatment for the patient, including product avoidance.

To Dye For: PPD and Other Allergenic Ingredients in Hair Dyes…continued

SØsted H, Rustemeyer T, Gonçalo M, et al: Contact allergy to common ingredients in hair dyes. Contact Dermatitis 69: 32-39, 2013

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Helen of Troy is said to have had a face that launched a thousand ships, but the British rock group, The Spice

Girls, may have had the body tattoos that launched a thousand cases of allergy to para-phenylenediamine (PPD). Specifically, allergic skin reactions to black henna tattoos have been increasing since 1997 when these entertainers became extremely popular. As noted in the previous article, hair dyes are the primary source of sensitization to PPD. But temporary tattoos, applied by using a paste made from a mixture of PPD and red henna, are now thought to sensitize an estimated 2.5% of those exposed. Given that only severe cases reach medical attention and that unregulated temporary tattoos applied by tattoo artisans are fashionable at vacation and holiday sites such as beaches and amusement parks, the prevalence of sensitization related to these tattoos is likely underestimated.

Red henna, the dried and powdered leaf of the small shrub Lawsonia inermis, has been used to decorate the body for thousands of years and represents little risk to humans. Given that half of the population of India is thought to be exposed to henna at some point during their life, its sensitizing potential appears to be minimal. Although 19 possible cases of allergic contact dermatitis have been reported, the presence of PPD and other aromatic amines as the causative agent(s) cannot be ruled out in some of the cases. Thus red henna is relatively benign. When PPD is added to red henna as a darkening agent, however, the situation changes dramatically.

Black henna tattoos may be perceived as “natural” and as safe because the skin does not need to be penetrated and infectious agents are not introduced. As a result these temporary tattoos are especially popular among young people. Yet PPD is an extreme sensitizer—enough so that the German Contact Dermatitis Research Group removed 1% PPD from their baseline series as discussed in the previous article. And the concentrations that consumers are exposed to in henna dyes far exceed 1%. The concentrations of PPD (% wt/wt) in black henna samples tested by the Food and Drug Administration in the United States have ranged from more than 4 to 27%. Investigations have found that PPD concentrations in henna were as high as 29% in the United Arab Emirates and soared to as high as 64% in Spain while in Germany the average concentration was more than 6%.

Blame it on the Spice Girls: Henna Tattoos and Sensitization to PPD

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Blame it on the Spice Girls: Henna Tattoos and Sensitization to PPD…continued

Allergic contact dermatitis related to PPD is often confined to the site of the tattoo, appearing within 1-3 days in individuals already sensitized and within 4-14 days in those undergoing initial sensitization. Generalized dermatitis can also occur. Hypo- and depigmention have been reported, and hyperpigmentation lasting more than 6 months is relatively common. Localized hypertrichosis has also been observed. Besides these delayed Type IV reactions, PPD has been associated with life-threatening Type I immediate reactions such as edematous swelling of the airway causing respiratory distress and requiring hospitalization for emergency treatment.

Tattoos are widespread. A survey from Denmark found that a third of the respondents from the general population had tattoos and the proportion increased with related occupations (e.g., hairdressing apprentices) while in the United Kingdom 7% of 4000 adults and 14% of their children had had a temporary tattoo. The risk of sensitization to PPD from tattoos especially becomes a major concern for children. Besides hair dyes and henna tattoos, PPD is common in many products that may need to be avoided: leather, fur, textiles, black rubber, paints, and printing inks to name just a few. Occupational choices may be restricted because PPD is a common allergen in many professions such as printing; hairdressing; and the shoe, chemical, leather, rubber, plastic, paper, and textile industries.

Although not of epidemic proportions, the prevalence of allergic contact dermatitis to PPD continues to increase. In the European Union (EU), this increase continues despite the launch of a campaign backed by the European Commission to educate the public about the serious health issues associated with black henna tattoos. In both the EU and the United States, hair color is the only cosmetic allowed to contain PPD. Nonetheless, most countries have no regulations on the use of black henna in tattoos. In his recent comprehensive review of henna tattoos on which this discussion is based, de Groot suggests that health legislation is needed to minimize the opportunities for sensitization to PPD. In the meantime, medical professionals need to be aware of this growing public health problem and how to diagnose allergic contact dermatitis to PPD with patch

testing, how to treat its many manifestations, and how to develop strategies to help their patients avoid the allergen. Ultimately, intensive education of the public will be needed to discourage the use of black

henna tattoos to avoid further sensitization.

de Groot AC: Side-effects of henna and semi-permanent ‘black henna’ tattoos: a full review.

Contact Dermatitis 69: 1-25, 2013

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IMPORTANT SAFETY INFORMATIONINDICATIONS AND USAGE:T.R.U.E. TEST is an epicutaneous patch test indicated for use as an aid in the diagnosis of allergic contact dermatitis in persons 18 years of age and older whose history suggests sensitivity to one or more of the 35 substances included on the T.R.U.E. TEST panels.

CONTRAINDICATIONS• Do not apply to skin of patients with

a history of severe allergic reaction (systemic and/ or local) to any of the allergen components or inactive substances of T.R.U.E. TEST.

• Do not apply to skin that is injured or inflamed.

WARNINGS AND PRECAUTIONS• Acute allergic reactions, including

anaphylaxis, may occur.• Sensitization to one or more of the

allergens may occur with initial or repeat testing.

• Extreme positive reactions, excited skin syndrome, tape reactions, irritant contact dermatitis, persistent reac-tions, and late reactions at the test site may occur.

ADVERSE REACTIONS• The most common adverse reactions

(occurring in more than 1% of the study population) were burning, tape irritation, persistent reactions, erythe-ma, and hyper/hypo pigmentation.

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