When allergic contact dermatitis (ACD) is caused by hair dye, it is known as a hair dye contact allergy (HDCA), and it is usually observed among people who dye their hair and among hairdressers. Para-phenylenediamine (PPD) is a chemical within many hair dyes that is a major cause of HDCA1,2. Although PPD was the most common cause of ACD in the 1970s, it received less attention than ammoniated mercury and nickel sulfate during the 1980s and 1990s, respectively, because of changes in the natural environment3. However, since the beginning of the 2000s, PPD has been receiving attention again as an allergen because of the heightened demand for hair dyeing, particularly among middle-aged individuals4.

PPD is highly irritable and toxic, and the American Contact Dermatitis Society considered it the allergen of the year in 2006. PPD was banned in Sweden and France, but its use was resumed later in the European Union1. Standard manufacturing practices for quasi-drugs established by the Korea Food and Drug Administration state that the permissible level of PPD is 3%; consequently, most hair dyes on the Korean market contain PPD at a level of ≤3%. Patients with ACD caused by toluene-2, 5-diamine or aminophenol, which can cross-react with PPD, have been reported, but the most effective marker of HDCA is PPD5,6,7. Additional studies on other agents that cause HDCA may be required in the future.

The thin-layer rapid use epicutaneous (TRUE) Test (Smart-Practice, Phoenix, AZ, USA) is a patch test that was introduced to Korea in 2005. Subsequently, it replaced the Korean standard series 25, because it has a quantitative antigen, shows a high level of reproducibility, and is easy to use in the diagnosis of ACD8. The TRUE Test contains 24 antigens that are considered the causative agents in approximately 80% of all ACD cases. Antigen number 20 in the TRUE Test system is comprised of 90 µg/cm² of PPD. No studies in Korea have described the simultaneous sensitivities to hair dyes used by individuals or the PPD based on the results from patch tests using the TRUE Test system. In this study, the patch tests were conducted with hair dyes used by the patients to determine the PPD contribution to HDCA, and the PPD-positive rate determined by the TRUE Test was investigated in those patients who showed positive reactions to their own hair dyes. Lastly, we also investigated the patients' awareness about hair dyes as agents that cause HDCA.

Hair is not just a skin appendage; it is used to express people's individuality, wellbeing, and attributes. Consequently, hair dyeing is widely accepted among younger people as a way to express youthfulness and color preferences, and among older people as a way to darken their graying hair9. The size of the Korean market for hair dye is expected to grow further with increases in women's social activities and the mean life span.

Modern hair dyeing began in 1893 when Hoffmann of Germany synthesized PPD and dyed hair at a low temperature, and this helped formed the basis of the oxidative hair dyes that are widely used today10. Oxidative hair dyes are composed of a hair coloring solution, which is the first component, and an oxidizing solution, which is the second component. Immediately before dyeing the hair, the two solutions are mixed, and then they are applied to the area to be dyed and are left on for some time. During this time, bleaching caused by the hydrogen peroxide in the second component and polymerization of the hair dye occur simultaneously to produce a new color. As the hair is dyed, the compounds in the hair dye are absorbed by the skin, which induces changes in the stratum corneum, and this may be accompanied by direct damage to the hair structure, leading to the development of ACD11. In Denmark, Søsted et al.12 showed that 5.3% of people who dye their hair experience adverse allergic skin reactions. In Korea, ACD is not as widely acknowledged as skin damage that is caused by hair dyes, and most patients do not understand that ACD is a consequence of skin damage caused by hair dyes, despite them being classified as medicinal products.

The most frequently suspected allergen that causes HDCA is PPD. The PPD sensitization rate within the general population is 1%~6%, and among patients who are highly likely to have HDCA, the PPD sensitization rate is reportedly 38%~97%13. Accordingly, PPD can be used as an effective marker of HDCA. PPD is included in the TRUE Test as antigen number 20, and positive reactions to PPD have gradually increased over time. Thyssen and White1 reported that the median prevalence of PPD sensitization in Asia was 4.3%, and it is consistently increasing. Patel et al.'s4 study showed that the rate of PPD sensitization rose sharply from 3.8% in 1989 to 7.1% in 2004 in the United Kingdom. A retrospective study conducted by Handa et al.14, which targeted 116 patients in India between 2009 and 2010, reported positive reactions to PPD in 19 (16.4%) patients, and that was an 11.7% increase from that found in a previous study that was conducted in the same country between 1999 and 2000. In a Korean study conducted by Lee et al.3, the positive reaction rate to PPD was reported as 5.7% between 2000 and 2006, and Hong et al.8 reported a positive reaction rate to PPD of 8.4% between 2009 and 2010, which was higher than the rate reported in a previous study3. The increase in PPD sensitization relates to the increase in the demand for hair dyes. Furthermore, PPD is not only present in hair dyes, but it is also present in henna tattoos, which are popular among younger people and are considered to have contributed to the increase in PPD sensitization15,16,17,18.

Of the 84 subjects in the current study who underwent patch tests because they were suspected to have HDCA, 45 (53.6%) had positive reactions to the hair dyes that they regularly use, and they were definitively diagnosed with HDCA. Of the 84 study subjects, 21 (25.0%) had a positive reaction to PPD in the TRUE Test, and of the 45 subjects who were diagnosed with HDCA, 18 (40.0%) had a positive reaction to PPD in the TRUE Test. Therefore, PPD was confirmed as an effective marker of HDCA in the current study on the basis of the statistically significant correlation between the positive reaction rates to the hair dyes that the subjects regularly use and the positive reaction rates to PPD, and this finding concurred with those from previous studies. However, since only 40% of the subjects with HDCA had positive reactions to PPD, additional studies to determine and validate other markers of HDCA in patients who show a negative reaction to PPD may be required. For example, additional patch tests with toluene-2,5-diamine, p-aminophenol, m-aminophenol, and o-aminophenol, which with the exception of PPD are the most frequently documented ingredients in hair dyes, may help to analyze the contribution of each of these ingredients to HDCA6,19,20.

Among the 45 subjects who were diagnosed with HDCA in this study, hair dyeing had most commonly been performed for 1~5 years (15 subjects, 33.3%). In many patients, the onset of dermatitis occurred within 1 week of the hair being dyed (16 subjects, 35.6%). Hair was commonly dyed >10 times per year (17 subjects, 37.8%). However, these behaviors associated with hair dyeing did not correlate with the positive patch test reactions to PPD. HDCA was most commonly observed on the subjects' foreheads (33 subjects, 73.3%), and pruritus was the most common clinical symptom (44 subjects, 97.8%). When comparing our study's findings to those reported by Søsted et al.7, the frequencies of edema and ulceration in our study were significantly lower than that of pruritus. In the present study, no severe acute allergic reactions such as conjunctivitis, dizziness, swollen lymph nodes, breathing difficulties, or headaches occurred, which Søsted et al.7 previously reported. Moreover, higher levels of allergic reactions were observed near the forehead, eyes, and ears than on the scalp, which is the area that has the greatest direct contact with hair dyes. Furthermore, the relatively mild clinical symptoms and the mismatch between the distribution of the skin lesions and the application area for the hair dye may mean that patients with HDCA fail to suspect that hair dyes contain allergens.

The most important point to note from this study is that of the 45 subjects who were diagnosed with HDCA, only 7 (15.6%) identified hair dyes as containing allergens. Indeed, only a few subjects who had allergic reactions to the hair dyes accepted that the hair dye they were using contained an allergen. However, people who have had HDCA at least once may develop considerably more severe allergic reactions if they are exposed to the same allergen again; thus, it is very important to accurately diagnose the condition and its underlying causes. To minimize the risk associated with allergic reactions, patients must understand the pathogenesis and clinical course of HDCA and also avoid hair dyeing. If this is unavoidable, patch tests are recommended before hair dyeing is attempted. As shown in this study, hair has often been dyed for years with few severe adverse reactions; therefore, most patients do not suspect that their hair dyes contain major allergens that cause the development of ACD. Besides, patients often reject the concept that hair dyes contain allergens even when dermatologists advise them of this possibility. As stated previously, hair dyes are barely acknowledged as the primary causative agents for the HDCA that develops in areas other than the scalp. Hence, patients suspected to have HDCA must be informed about the importance of undergoing patch tests. However, while the patch test is regarded as a gold standard method for diagnosing ACD, its utility is a topic of ongoing debate21. Despite efforts to standardize the allergens, vehicles, and concentrations to enhance the reproducibility of the patch tests, it is often difficult to identify the causative allergens because of the test techniques, reading or exposure times, and cross-reactions22,23,24,25. Therefore, patch tests should be conducted and interpreted by experienced dermatologists. Furthermore, since PPD can cross-react with its own derivatives and other components in hair dyes and induce irritant reactions as well as typical allergic reactions, greater attention should be paid to the interpretation of patch-test results.

The significance of this study lies in its focus on PPD sensitization, the behaviors associated with hair dyeing, and the clinical characteristics of Korean HDCA cases that have not been actively investigated before, despite their frequent occurrence. Nevertheless, since this study was conducted at a university hospital and it only targeted urban patients, it was limited because it did not emulate PPD sensitization across the entire Korean population. Further large-scale multicenter studies that investigate PPD sensitization categorized according to regional and demographic characteristics may help explain the prevalence and clinical features of HDCA in Korea. In addition, feasibility studies that investigate the commercialization of patch tests, which include the components of hair dyes other than PPD, may be required to help explain the mechanisms underlying HDCA, its diagnosis, and treatment.