Contact allergy to hair colouring products The cosmetovigilance experience of 4 companies (2003-2006)

ARTICLE

Auteur(s) : Maya Krasteva¹, Brigitte Bons¹, Sarah Tozer², Kim Rich², Edo Hoting³, Detlef Hollenberg³, Anne Fuchs⁴, Rolf Fautz⁴

¹L’Oréal Research and Development, 25-29 quai Aulagnier, 92600 Asnières, France
²P&G Technical Centres, Rusham Park, Whitehall Lane, Egham, Surrey, TW20 9NW, UK
³Henkel AG & Co. KGaA, Henkelstr. 67, 40589 Düsseldorf, Germany
⁴KPSS – Kao Professional Salon Services GmbH, Pfungstaedter Strasse 92 – 100, 64297 Darmstadt, Germany

accepté le 17 Août 2009

Oxidative hair dyes have repeatedly come to the attention of the dermatological community due to concerns of contact sensitivity (type IV allergic reactions). It has recently been stated that contact allergy to p-phenylenediamine (PPD) has increased significantly in the general population in the recent decades [1, 2]. Two exhaustive reviews of epidemiological data on consumer allergy to PPD, however, showed no clear increase of positive patch tests to PPD in eczema patients and in the general population in Europe over the last 40 years [3, 4]. All the parameters through which the frequency of hair dye dermatitis was evaluated have been stable in Europe with a few exceptions [4].

This paper analyses post-marketing undesirable events (UEvs) to hair colouring products notified to the cosmetovigilance departments of four major companies in the European Union in a 4-year period. These companies are referred to as Company 1, 2, 3 and 4. To date, no paper has been published on post-marketing surveillance data of hair colouring products.

The objective of the analysis was to determine whether there was any:

• – time effect (trend to increase or decrease of notified undesirable events and effects);
• – country effect (significant difference between the countries included in the analysis);
• – product type effect (direct or oxidation);

as well as to identify risk factors.

Material and methods

Spontaneous reporting and post-marketing surveillance procedures

A spontaneous report is an unsolicited communication by a consumer, a healthcare professional, a regulatory authority or another organisation that describes an undesirable reaction in a consumer who used a cosmetic product.

Monitoring of spontaneous reporting is an efficient method for capturing changes in market place acceptance or tolerance of products and can provide important information on “at-risk groups”, risk factors, and clinical features of known serious undesirable reactions. Caution should be exercised in evaluating spontaneous reports, especially when comparison is made between different countries or between companies where cosmetovigilance systems are implemented differently. The rate at which cases are reported is dependent on many factors, including the time since product launch, cultural consumer habits, media attention or environmental/public health concern and current national regulatory requirements on cosmetovigilance.

In countries or in companies where cosmetovigilance has been implemented for several years, spontaneous reporting gives a meaningful indication on reporting rate. The reporting rate is based on the number of spontaneously reported undesirable events (the numerator) and the population exposure (the denominator). Reporting rates are not incidence rates; they are, however, a useful indicator to identify and describe a signal.

Cosmetic companies conduct post-marketing surveillance by collecting undesirable events that have occurred during or after use of their products. In 2005, Colipa issued “Guidelines on the Management of Undesirable Events, Final version adopted by Board of Directors, August 23, 2005” which describes the consistent processes to be implemented by the cosmetic industry [5]. These guidelines provide methodology on receiving, centralizing, recording and analyzing genuine undesirable event reports, allowing the consistent generation of high quality and reliable data, using a common method of causality assessment.

The processes in place for collecting undesirable events are similar between the cosmetic companies concerned. Complaints related to intolerance are reported to persons responsible locally in the different countries. All available medical information on an initial complaint is collected, including the results of complementary investigations if performed (such as patch tests in case of suspected allergic reactions). It is important to underline that cosmetovigilance is mainly based on consumer self-reporting and as such not all the medical information required for reliable assessment is available in all cases.

Causality assessment

Undesirable events (UEvs) given a causality assessment of “likely” or “very likely” are classified as undesirable effects (UEfs), which are reasonably attributable to product use (figure 2).

An event is qualified as a serious or non-serious undesirable event/effect depending on the objective symptoms, the outcome or the necessity of specific treatment (WHO and ICH guidelines). Serious events are those that are i) fatal; ii) life-threatening; iii) permanently/significantly disabling; iv) require or prolong hospitalization; v) cause congenital anomaly or vi) require intervention to prevent permanent impairment or damage.

Products

• – Oxidation (permanent, demi-permanent/tone on tone) hair dyes (approximately 80 to 90% market share);
• – Direct (semi-permanent and temporary) hair dyes (approximately 10% to 20% of market share).

Different brands of both types are marketed for home use and for professional use. Some of the hair dye manufacturers market only professional use products.

Company 1 presents data on both professional and home use products; Companies 2 and 3 present data only on home use products, due to missing reporting from professionals in the past and, in some instances, to lack of sales figures, and Company 4 presents data only on professional products.

Data collection and reporting rates

From these data, three main series of reporting rates are provided:

European reporting rates for all types and levels of causality assessment of alleged UEvs

Yearly and country rates of UEvs were calculated for all hair colouring products and, separately, for oxidation and for direct hair colouring products.

European reporting rates for UEfs (causality assessment likely and very likely) with manifestations compatible with allergic contact dermatitis

Specific analysis of UEvs and UEfs (causality assessment likely and very likely) related to the use of oxidation hair colouring products in selected countries

• – Each Company has a large and/or stable sales market;
• – The cosmetovigilance processes have been efficient for a significant period;
• – Northern and Southern European regions are covered.

For this specific analysis, data are issued from:

• – 3 countries for Company 1 (UK, France, Germany);
• – 4 countries for Company 2 (UK, Sweden, Spain and Greece);
• – 7 countries for Company 3 (UK, Germany, Scandinavian countries (4 countries), France);
• – 1 country for Company 4 (Germany).

The following (I to VI) reporting rates were calculated for each year from 2003 to 2006, for each selected country and when feasible, for each product distribution network (home use or salon): I) All types of undesirable effects to oxidation hair colouring products; II) A breakdown of undesirable effects into allergic contact dermatitis and scalp and skin irritation [6, 7]; III) Oedematous-type contact allergic dermatitis cases. Oedema is taken as an indication that the reaction is severe; IV) Serious cases of allergic contact dermatitis; V) Allergic contact dermatitis following the use of black henna tattoos. The reporting rates concerning black henna tattoos will be given separately for serious and non serious cases of allergic contact dermatitis; VI) The age distribution for serious and non serious undesirable effects compatible with allergic contact dermatitis.

All data are normalised against the units of product sold (number/million units sold).

Statistical methods

Reporting rates in different countries for the same company and reporting rates to different types of products (direct vs oxidation hair colour) or distribution networks (professional vs home use) were compared and analysed using a Chi-square test. When p < 5%, it was considered that there was a statistically significant difference between 2 countries, types of products or distribution networks. When p > 5% it was considered that there was no statistical difference between 2 countries, types of products or the 2 distribution networks. But it could be considered that a trend exists if p is between 5 and 10%.

The influence of having a henna tattoo on the reaction type (serious reaction or non serious reaction), was analyzed by comparing with a Chi-square test the rate of having a serious reaction among people who had an undesirable event, according to whether they have had a henna tattoo or not. When p < 5%, it was considered that there was a statistically significant difference in the incidence of serious UEfs in the group of consumers with past history of black henna tattoos and the incidence of severe UEfs in the group of consumers with negative or unknown history of black henna tattoo applications. When p > 5% it was considered that there was no statistically significant difference in the incidence of severe UEfs in the two groups.

It was not possible to do a statistical analysis on the age distribution of serious UEfs as the actual number of units sold to each age group is unknown.

Results

European reporting rates on all types of alleged UEvs (all type of events, all levels of causality assessment)

Country yearly rates were calculated for all kinds of hair colouring products together, and then for oxidation and direct hair colour separately. The yearly European rates for the four companies are shown in table 1. There is no time effect for the European area as a whole for any of the companies, for all hair colouring products and for the two product types analysed separately. The UEvs rates to direct hair colour were significantly lower than to oxidation hair colour for 3 of the 4 companies; there was no statistically significant difference between product types for Company 2.
Table 1 European reporting rates of undesirable events (UEvs, all levels of causality assessment) for all hair colouring products and separately, for oxidation and direct hair colouring products. Rates are calculated as the number of UEvs per million of units sold

European reporting rates for UEfs with manifestations compatible with allergic contact dermatitis (causality assessment likely and very likely)

The analysis of these rates for time effect shows that there is no significant increase or decrease with time for any company reporting in the European area as a whole, neither for allergic contact dermatitis related to oxidation hair colouring products nor for allergic contact dermatitis related to direct hair colouring products.

These data show that the reporting rates of UEfs compatible with allergic contact dermatitis to direct hair colouring products are significantly lower than the reporting rates to oxidation hair colouring products for each company.

European reporting rates on the 4-year period for each of the companies are presented in table 3. These include alleged UEvs prior to medical assessment and reporting rates for UEfs compatible with allergic contact dermatitis. These rates have been calculated for the two types of hair colouring products together and then separately.

Table 3 shows that the incidence of allergic contact dermatitis related to hair colouring products is significantly less than the incidence of all alleged UEvs. This is true both for oxidative and direct dyes. The incidence of allergic contact dermatitis related to direct hair colouring products is lower than the incidence for oxidative hair colouring products.
Table 2 European reporting rates of undesirable effects (UEfs) with manifestations compatible with allergic contact dermatitis (causality assessment likely and very likely) for oxidation and direct hair colouring products. Rates are calculated as the number of UEfs per million of units sold

Specific analysis on oxidation hair colouring products in selected countries

Time and Country effect on UEvs and UEfs reported with oxidation hair colouring products

Time effect

Country effect

Effect of Home use versus Salon use on rates of alleged UEvs and UEfs due to oxidation hair colouring products

Type of manifestations and henna tattoo effect on the severity of the reaction

Oedema was used as a criterion of greater severity throughout the period, the definition of a serious undesirable event becoming available only in 2005 (Colipa Guideline on the management of undesirable event reports) [5]. Serious UEvs were less than 5% of all UEvs notified to companies.

As shown in table 6, there was a known history of black henna tattoo application in a significant number of serious undesirable events: 50% for Company 1 (2006). For other companies who started more recently to collect data on henna tattoos, an indication of association is also observed. However, in a great number of cases, exposure to black henna tattoos cannot be characterised: it is difficult to obtain an answer from the consumers due to different reasons inherent to spontaneous reporting methods (in many cases people cannot be contacted directly by company for a more detailed questionnaire).

To better characterise the importance of black henna tattoos in the elicitation of serious UEfs to hair colouring products, the incidence of serious undesirable effects in consumers with known black henna tattoo applications has been compared to the incidence of serious undesirable effects in consumers with unknown or absent black henna tattoo application, for each Company. The incidence of serious undesirable effects was calculated as follows:

• – for consumers with known black henna tattoo applications, the percentage of people who had a serious reaction among all the people who had a reaction (serious or not serious) and who declared that they had a black henna tattoo application;
• – for consumers with unknown or absent black henna tattoo applications, the percentage of people who had a serious reaction among all the people who had a reaction (serious or not serious) and who declared that they had no black henna tattoo application.

The comparison between the incidence of serious UEfs in consumers with known black henna tattoo applications to the incidence of serious UEfs in consumers with unknown or absent black henna tattoo applications (table 7) shows that there is a statistically significant difference for Company 1 and for the three companies together (p < 0.001, Chi-square test). Black henna tattoo application increases by more than four times the reporting of occurrence of a serious reaction to hair colouring products.
Table 6 Type of manifestations to oxidation hair colouring products and effect of black henna tattoos on the seriousness of the reaction. Rates are calculated as the number of UEfs per million of units sold

Age effect on serious and non-serious UEfs with manifestations compatible with allergic contact dermatitis

It should be taken into consideration that the serious undesirable events with known exact age are over-represented on the graph compared to the non-serious events with known age because age is known in almost all cases of serious adverse events. Although it was not possible to get the actual number of units sold for each age to allow for statistical analysis, it can be visually observed that serious undesirable events apparently occur at a higher frequency in the younger age groups in the UK (Company 1).

Discussion

Review of reporting rates

Level of incidence

Spontaneous notifications: alleged UEvs

Incidence of contact allergy related to hair colouring products

Historically, consumers in the UK have always had a higher rate of reporting of undesirable events for all types of cosmetic products. The data presented here for the hair colour category reflects the same trend. However, there is no specific concern with these incidence rates.

The incidence of adverse skin reactions to hair colouring products in Europe is comparable to other types of cosmetic products as reported in consecutive eczema patients [9, 10], cosmetovigilance studies (notifications by health professionals) [11] and in consumer complaint-based studies [12, 13].

Analysis of cases of allergic contact dermatitis to oxidation hair dyes in our study showed some unusual clinical features (pronounced facial oedema) in a small subset of consumers; the outcome of these cases is the same as the one described in classical contact dermatitis. The percentage of serious cases notified to companies (< 5%) appears to be lower than that which is found by regulatory authorities (15-27%) [14, 15]. As we believe that there is less under-reporting for serious UEvs than for non-serious UEvs and that almost all serious UEvs are finally notified to companies, one possible explanation could be the different source of notifications. The public cosmetovigilance systems are notified chiefly by dermatologists and dermatologists see more severe cases; as consumers are the main actors in private cosmetovigilance systems, this allows the companies to have a more exhaustive view on all the diverse manifestations with varying levels of severity.

Analysis of main parameters examined across companies

Time effect (for the whole European area)

Country effect

• – A trend for an increase in alleged UEvs to all hair colouring products (oxidation and direct) in Austria (new market) and Finland (very low level of complaints, not allowing a meaningful analysis) (Company 2).
• – A trend for an increase in alleged UEvs to oxidation hair colouring products in Scandinavian countries due to restructuring and improved data collection (Company 3).
• – A trend for an increase in UEfs to oxidation hair colour was seen in Greece (very low level of complaints, not allowing a meaningful analysis) (Company 2).

Four-year reporting rates for medically confirmed UEfs to oxidation hair colouring products are similar in all countries within the same company with a few exceptions:

• – UK, with significantly greater rates for medically confirmed UEfs, allergic contact dermatitis, oedematous allergic contact dermatitis and serious undesirable events (Company 1).
• – UK and in Sweden with higher rates of oedematous contact dermatitis compared to Spain and Greece (Company 2).

Product type effects

The same caution should be taken when assessing differences between rates to Home use products versus Professional products; an under-reporting of UEs from the distribution circuit of Professional products compared to Home use products contributes to these differences.

Risk factors

The impact of black henna tattoos has been acknowledged by some health authorities in the last few years. In France, since 2006, Afssaps has conducted a consumer awareness campaign on the risks associated with this practice [15, 27]. In 2008, the European Commission launched a campaign in all member states to provide information to the public that black henna tattoos can cause serious health injuries [28].

Conclusion

The incidence of adverse skin reactions following the use of hair colouring products is comparable with other cosmetic product types, although some reactions can be more serious. Some severe allergic contact dermatitis to oxidative hair colouring products has been observed in a subset of consumers. The analysis of these cases shows that a key contributory risk factor identified for these events is previous application of black henna tattoos.

In recognizing some of the safety concerns, the industry has gradually increased the safety labeling of hair colouring products through the years. Product labels now include, besides the ingredient listing, warning statements alerting users, (i) that hair colourants may cause reactions which may be severe, (ii) not to apply products in people who have already experienced some reactions, and (iii) increased allergy risk as a result of previous exposure to black henna tattoos. In addition, there is a recommendation to conduct a skin alert/compatibility test before proceeding to colour the hair [29, 30].

In conclusion, hair colouring products may be used by consumers with the same level of confidence as other cosmetic products, provided that use instructions are followed carefully. In some cases where follow-up was more thorough or more information was available, it is clear that some consumers did not follow the use and safety instructions recommended. Prospective studies are needed to understand risk and risk factors in the younger age groups (< 16 years).

Acknowledgements

References

2 McFadden JP, White IR, Frosch PJ, Sosted H, Johansen JD, Menne T. Allergy to hair dye. Br Med J 2007; 334: 220.

3 Thyssen JP, White JM, European Society of Contact Dermatitis. Epidemiological data on consumer allergy to p-phenylenediamine. Contact Dermatitis 2008; 59: 327-43.

4 Krasteva M, Bons B, Ryan C, Gerberick GF. Consumer allergy to oxidative hair colouring products: Review of epidemiological data published in the literature. Dermatitis 2009; 20: 123-41.

5 Colipa Guidelines on the Management of Undesirable Event Reports. 23 August, 2005.

6 Coenraads PJ, Gonçalo M. Contact dermatitis. Eur J Dermatol 2007; 17: 564-5.

7 Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF. Allergic and irritant contact dermatitis. Eur J Dermatol 2009; 19: 325-32.

8 Duarte I, Campos Lage AC. Frequency of dermatoses associated with cosmetics. Contact Dermatitis 2007; 56: 211-3.

9 Berne B, Tammela M, Färm G, Inerot A, Lindberg M. Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol. Contact Dermatitis 2008; 58: 223-7.

10 Lindberg M, Tammela M, Boström A, et al. Are adverse skin reactions to cosmetics underestimated in the clinical assessment of contact dermatitis? A prospective study among 1075 patients attending Swedish patch test clinics. Acta Derm Venereol 2004; 84: 291-5.

11 Sportiello L, Cammarota S, de Portu S, Sautebin L. Notification of undesirable effects of cosmetics and toiletries. Pharmacol Res 2009; 59: 101-6.

12 Berne B, Lundin A, Malmros PE. Side effects of Cosmetics and toiletries in relation to use. A retrospective study in the Swedish population. Eur J Dermatol 1994; 4: 189-93.

13 Di Giovanni C, Arcoraci V, Gambardella L, Sautebin L. Cosmetovigilance survey: are cosmetics considered safe by consumers? Pharmacol Res 2006; 53: 16-21.

14 Council of Europe. Resolution ResAP(2006)1 on a vigilance system for undesirable effects of cosmetic products (“cosmetovigilance”) in Europe in order to protect public health. (Adopted by the Committee of Ministers on 8 November 2006 at the 979th meeting of the Ministers’ Deputies).

15 Abbadi NH, Artigou C, Laurent A, Desmares C. Cosmetovigilance: review of the adverse effects reported to Afssaps in 2007. In : 17^th EADV Congress, Paris 2008.

16 Brancaccio RR, Brown LH, Chang YT, Fogelman JP, Mafong EA, Cohen DE. Identification and quantification of para-phenylenediamine in a temporary black henna tattoo. Am J Contact Derm 2002; 13: 15-8.

17 Marcoux D, Couture-Trudel PM, Riboulet-Delmas G, Sasseville D. Sensitization to para-phenylenediamine from a streetside temporary tattoo. Pediatr Dermatol 2002; 19: 498-502.

18 Redlick F, DeKoven J. Allergic contact dermatitis to paraphenylendiamine in hair dye after sensitization from black henna tattoos: a report of 6 cases. CMAJ 2007; 176: 445-6.

19 Kazandjieva J, Grozdev I, Tsankov N. Temporary henna tattoos. Clin Dermatol 2007; 25: 383-7.

20 Jacob SE, Zapolanski T, Chayavichitsilp P, Connelly EA, Eichenfield LF. p-Phenylenediamine in black henna tattoos: a practice in need of policy in children. Arch Pediatr Adolesc Med 2008; 162: 790-2.

21 Onder M. Temporary holiday “tattoos” may cause lifelong allergic contact dermatitis when henna is mixed with PPD. J Cosmet Dermatol 2003; 2: 126-30.

22 Raboobee F. Sensitisation from PPD in temporary henna tattoos and subsequent severe allergic contact dermatitis from hair dye. Curr Allergy Clin Immunol 2004; 17: 195-8.

23 Jasim ZF, Darling JR, Handley JM. Severe allergic contact dermatitis to paraphenylene diamine in hair dye following sensitization to black henna tattoos. Contact Dermatitis 2005; 52: 116-7.

24 Sosted H, Johansen JD, Andersen KE, Menné T. Severe allergic hair dye reactions in 8 children. Contact Dermatitis 2006; 54: 87-91.

25 Hink E, de Winter JP. Hair-dye allergy: a coloured case. Eur J Pediatr 2006; 165: 195-6.

26 Shavit I, Hoffman Y, Shahor-Meyouhas Y, Knaani-Levinz H. Delayed hypersensitivity reaction from black henna tattoo manifesting as severe facial swelling. Am J Emergency Med 26; 2008: 515.e3-515.e4.

27 Afssaps, http://Afssaps.sante.fr : Communiqué de presse Tatouages éphémères à base de henné: mise en garde. 23 juin 2008.

28 European commission, http://ec.europa.eu. National campaign on black henna tattoos which can cause serious health injuries. 23.05.2008.

29 Krasteva M, Cristaudo A, Hall B, et al. Contact sensitivity to hair dyes can be detected by the consumer open test. Eur J Dermatol 2002; 12: 322-6.

30 Krasteva M, Cottin M, Cristaudo A, et al. Sensitivity and specificity of the consumer open skin allergy test as a method of prediction of contact dermatitis to hair dyes. Eur J Dermatol 2005; 15: 18-25.