Addressing the conundrums of p‐phenylenediamine hair dye allergy by applying Friedmann's principles of contact sensitization

In the first conundrum, permanent hair dyeing involves the use of aromatic amines such as p‐phenylenediamine (PPD), whose oxidation is pivotal to the dyeing process, but also generates potent allergens. Despite prolonged efforts by industry to search for safer alternatives, hair dyeing is still reliant on this type of aromatic amine. In the second conundrum, patch testing with 1% PPD remains the most useful screen for hair dye contact allergy. However, there is a very small but real risk of actively sensitizing the patient. Lowering the PPD concentration below 1% significantly reduces test sensitivity and diagnostic utility. Here, we argue that by applying Friedmann's principles of contact sensitization each conundrum can be addressed from a new perspective. These principles indicate that, when the exposed area of skin is small (<1 cm²), induction of contact allergy is sharply reduced, whereas elicitation of allergy is unaffected. Careful reflection on this principle suggests that we can predict where hair dye sensitization is most likely to occur, indicates a strategy to reduce the chance of contact sensitization occurring in consumers as a result of hair dyeing, and how we might mitigate the risk of active sensitization resulting from diagnostic patch testing.     

Patch testing with hydroxyethyl-p-phenylenediamine sulfate - cross-reactivity with p-phenylenediamine

Background. Adverse reactions to permanent hair dyes are frequent, and primarily result from sensitization to p‐phenylenediamine (PPD). Objectives. To investigate the degree of cross‐reactivity to a chemically similar dye, hydroxyethyl‐p‐phenylenediamine sulfate (HPPS), and whether this might be a dyeing alternative for patients who are sensitive to PPD. Method. HPPS was patch tested in two concentrations in a total of 216 patients suspected of having contact dermatitis caused by hair dyes and/or hair cosmetics. A regular use test with a hair dye containing HPPS was suggested to every patient who had had an adverse reaction to a PPD hair dye in the past. Results. Forty of 216 (19.9%) patients reacted to 1% PPD, whereas only 2/216 (0.9%) showed a positive reaction to 1% HPPS. Reactivity to 2% HPPS was only slightly higher (5/216, 2.3%). On the basis of the 43 PPD‐positive patients, the reactivity to 2% HPPS amounted to 12%; the corresponding figure for toluene‐2,5‐diamine was 15% (5/33). In a use test on two PPD‐positive patients with a hair dye containing HPPS, no adverse reaction was seen, even after several years of regular dyeing. Conclusions. HPPS may be an alternative hair dye for individuals not tolerating PPD‐containing dyes. However, cross‐reactivity with PPD and other aromatic amines may occur. HPPS is also a known sensitizer, and the risk of de novo sensitization can only be assessed by a controlled study on a large panel and under regular use conditions.     

Contact dermatitis to para‐phenylenediamine in hair dye following sensitization to black henna tattoos – an ongoing problem

Summary Background: The increased frequency of case reports of allergic contact dermatitis from non‐permanent black henna tattoos in recent years shows the popularity of this form of body painting. Patients and methods: Seven patients presented with allergic contact dermatitis after initial hair or eyelash dyeing. They all had a history of a previous reaction from a black henna tattoo. All were patch tested with the European standard patch test series and the standard supplemental series, as well as special series for dyes and hairdressers. Results: All seven patients showed a positive reaction in patch testing with para‐phenylenediamine (PPD) (0.3 % and/or 1.0 % in pet.). Five patients also had positive reactions to other dyes such as aminophenol, para‐toluene diamine, disperse orange and yellow and four patients reacted to benzocaine. These were interpreted as cross‐reactions. The time from sensitization by the black henna tattoo to the onset of allergic contact dermatitis after hair dyeing was an average of 6.2 years. Conclusions: The most common cause of allergic contact dermatitis after black henna tattoos is PPD. Both the long skin contact and the high concentrations of PPD increase the risk of sensitization. Allergic contact dermatitis may be followed by post‐inflammatory hyper‐ or hypopigmentation, scarring and lifelong sensitization, which can have occupational impact, especially for hair dressers and cosmeticians.     

Hair dye sensitivity testing: a critical commentary

Although the large majority of users do not experience adverse skin reactions to hair dye products, a minority do. Most serious among these are allergic skin reactions, commonly to p-phenylenediamine and its derivatives. The consumer or hairdresser is expected (by the manufacturer) to limit the chance of expression of allergy by conducting a 'sensitivity test', which should provide the consumer with an alert for possible allergic reactivity. However, a self-conducted consumer test can only be useful if it meets a number of important criteria, including evidence that the test protocol works, that it can and is likely to be used successfully by the consumer or hairdresser, and that it does not present a significant health risk (e.g. an increased risk of developing allergy). In short, as with any in vivo test, the benefit must outweigh the risks. In formulating such a test, it should be determined in advance what are the acceptable levels of specificity (correct identification of negatives) and sensitivity (correct identification of positives). It is our view that any hair dye sensitivity test, whether supplied by the hair dye manufacturer or a third party, should be able to answer these questions.     

Side‐effects of henna and semi‐permanent ‘black henna’ tattoos: a full review

Henna, the dried and powdered leaf of Lawsonia inermis, is widely used as a dye for the skin, hair, and nails, and as an expression of body art, especially in Islamic and Hindu cultures. As it stains the skin reddish‐brown, it is also called red henna. Black henna is the combination of red henna with p‐phenylenediamine (PPD), and is used for temporary ‘black henna tattoos’. This article provides a full review of the side‐effects of topical application of red and black henna, both cutaneous (allergic and non‐allergic) and systemic. Red henna appears to be generally safe, with rare instances of contact allergy and type I hypersensitivity reactions. In children with glucose‐6‐phosphate dehydrogenase deficiency, topical application of henna may cause life‐threatening haemolysis. Black henna tattoos will induce contact allergy to its ingredient PPD at an estimated frequency of 2.5%. Once sensitized, the patients may experience allergic contact dermatitis from the use of hair dyes containing PPD. There are often cross‐reactions to other hair dyes, dyes used in textiles, local anaesthetics, and rubber chemicals. The sensitization of children to PPD may have important consequences for health and later career prospects. Systemic toxicity of black henna has been reported in certain African countries.     

Contact allergy to common ingredients in hair dyes

Background. It is widely accepted that there is a molecular weight (MW) cut‐off of 500, such that single chemicals with MWs higher than 500 cannot be skin sensitizers. If true, this could serve as a useful principle for designing non‐sensitizing chemicals. Objectives. To assess whether the 500 MW cut‐off is a myth or a reality. Methods. A database of 699 chemicals tested for skin sensitization in guinea pigs or mice was analysed to establish the number of tested chemicals with MW > 500, and to establish whether any of these were sensitizers. Results. Only 13 (2%) of the 699 chemicals in the database have MW > 500. Of the 13 tested compounds with MW > 500 in the database, five are sensitizers and eight are non‐sensitizers. Conclusions. The 500 MW cut‐off for skin sensitization is a myth, probably derived from the widespread misconception that ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potency. The scarcity of sensitizers with MW > 500 simply reflects the general scarcity of chemicals with MW > 500.     

Cross‐elicitation responses to 2‐methoxymethyl‐p‐phenylenediamine in p‐phenylenediamine‐allergic individuals: Results from open use testing and diagnostic patch testing

Background

Allergic contact dermatitis caused by p‐phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2‐methoxymethyl‐p‐phenylenediamine (ME‐PPD) has been developed as an alternative hair dye for primary prevention. However, cross‐elicitation responses can occur in PPD‐allergic subjects.

Objectives

To compare cross‐elicitation responses to ME‐PPD in open use and diagnostic patch testing of PPD‐allergic subjects with hair dye‐related allergic contact dermatitis.

Methods

Reactions to ME‐PPD were investigated in 25 PPD‐allergic subjects by performing (1) 45‐minute open use testing with a hair dye containing 2.0% of either ME‐PPD or PPD, and (2) patch testing with increasing ME‐PPD concentrations (0.1%–2.0% pet.).

Results

Of the 25 PPD‐allergic subjects, 21 (84%) reacted to open use testing with a hair dye containing 2.0% PPD, and testing with 2.0% ME‐PPD led to cross‐elicitation in 12 (48%). When patch tested with increasing ME‐PPD concentrations, 13 (52%) cross‐reacted at 0.1% (lowest dose) and 21 (84%) at 2.0% (highest dose), indicating decreased reactivity as compared with published PPD dose‐response data.

Conclusion

In line with the decreased cross‐reactivity of ME‐PPD in hair dye open use testing, PPD‐allergic subjects show an attenuated cross‐elicitation dose response to ME‐PPD in patch testing.     

Metabolic alterations of DHEA and cholesterol sulphates in the hair of patients with acne measured by liquid chromatography–mass spectrometry

Please cite this paper as: Metabolic alterations of DHEA and cholesterol sulphates in the hair of patients with acne measured by liquid chromatography–mass spectrometry. Experimental Dermatology 2010; 19 : 694–696. Abstract: As the hormonal levels in scalp hair reflects the condition of skin appendage, the level of dehydroepiandrosterone‐3‐sulphate (DHEAS) and cholesterol sulphate (CS) was evaluated in scalp hair obtained from patients with acne. The hair samples were extracted by alkaline solution and were analysed by liquid chromatography–mass spectrometry coupled to column switching system. The levels of DHEAS in scalp hair of women with acne were higher (P < 0.001) than controls, while the levels of CS in scalp hair of women and men with acne were higher (P < 0.001) than both control subjects. Increased hair levels of both DHEAS and CS could indicate acne development because of its direct action or stimulatory effect on local enzyme activity. It may be also helpful to understand the pathogenesis of acne based on follicular retention hyperkeratosis and increased sebum production of both steroid sulphates.