Jonathan M. L. White

Epidemiological data on consumer allergy to p-phenylenediamine

Many women and men now dye their hair. p‐Phenylenediamine (PPD) is a frequent and important component of permanent hair dye products; exposure to it may cause allergic contact sensitization, acute dermatitis, and severe facial oedema. To increase our understanding of PPD allergy, we reviewed published literature containing PPD patch test data from dermatitis patients and individuals in the general population. This was performed to estimate the median prevalence and the weighted average of PPD sensitization and thereby assess the burden of PPD‐containing hair care products on health. Literature was examined using PubMed–MEDLINE, Biosis, and Science Citation Index. The median prevalence among dermatitis patients was 4.3% in Asia, 4% in Europe, and 6.2% in North America. A widespread increase in the prevalence of PPD sensitization was observed among Asian dermatitis patients. In Europe, a decrease in the 1970s was replaced by a plateau with steady, high prevalences ranging between 2% and 6%. The prevalence remained high in North America, although a decreasing tendency was observed. Contact allergy to PPD is an important health issue for both women and men. More stringent regulation and enforcement are required as public health measures to reduce the burden of disease that exposure to PPD has brought to populations.

p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

Background:  Positive patch test reactions to p‐phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary ‘tattoos’. Cross‐sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe reactions upon hair dyeing, there is a need for ‘current’ prevalence data on PPD sensitization.

p‐Phenylenediamine allergy: the role of Bandrowski's base

p‐Phenylenediamine (PPD) is a commonly used hair‐dye and a potent skin allergen. The mechanism of sensitization is unknown, as PPD is protein unreactive. We studied Bandrowskis base (BB), a PPD trimer, as well as 1,4‐benzoquinone (BQ), a PPD hapten. PPD patch‐test positive patients were patch‐tested to BB and BQ. All tests were negative to 0.01% BQ and 0.01% BB. Five of 14 (35.7%) tested had true positive reactions to 0.1% BQ. One percent BQ was found to be irritant. Seven of 43 tested (16%) were positive to either 0.1% or 1% BB. The positive reactions to BB were weak, even when PPD reactions were strong. Mice lymph node assay gave EC3 values of 0.14% for PPD compared with 0.03% for BB. Therefore, BB is approximately 10 times more potent than PPD, taking into account the molarity. We suggest that while PPD may act as a prohapten, there is probably a spectrum of antigenic determinants in vivo. BB may be bound or metabolized by keratinocytes before it reacts with Langerhans cells.

Cosmetics and Skin Care Products

Contact allergy to ingredients of cosmetics is one of the most frequent causes of contact allergy. While patients may report reactions to fragrance items, preservative allergy may not be suspected. The reaction typically resembles eczema on the face or hands, although any body site may be affected. Products left on the skin are much more likely to cause allergic reactions than rinse-off products. Common allergens include fragrances (e.g., hydroxyisohexyl-3-cyclohexene carboxaldehyde, isoeugenol, etc.), preservatives (e.g., formaldehyde and formaldehyde-releasers, MCI/MI, paraben esters, etc.); hair dye chemicals (e.g., p-phenylenediamine), and less frequent allergens such as lanolin and propylene glycol. Patch testing is mandatory where allergy is suspected or in localized/difficult-to-treat eczema. Sometimes a repeated open application test (ROAT) is required when the patch tests are surprisingly negative. Mandatory ingredient labeling of cosmetic items in the EU facilitates allergen avoidance and EU-set limits on the concentration of known allergens seem to be reducing the incidence of allergic contact dermatitis to certain preservatives.

Baseline series fragrance markers fail to predict contact allergy.

Negative patch test results with fragrance allergy markers in the European baseline series do not always predict a negative reaction to individual fragrance substances.

Outbreak of methylisothiazolinone allergy targeting those aged ≥40 years

Methylisothiazolinone (MI) has been used in a combination of 1:3 with methylchloroisothiazolinone (MCI) since the 1980s. It has been used in toiletries, household products, wall paints, and industry (1). This combination has represented an important cause of preservative contact allergy with regard to its use in consumer products and paints. The MCI/MI combination has been regulated to an upper limit of 15 ppm in household products and cosmetics (i.e. MI concentration of 3.75 ppm) (2). In 2000, MI, which is claimed not to be as potent a sensitizer as MCI, was released onto the market as a single-agent preservative. A published EC3 value of between 0.4 and 2.2, depending upon the vehicle, categorized MI as a ‘moderate’ sensitizer (3). MI was first used in industrial products and paints, and the first case of allergic contact dermatitis caused by MI through occupational exposure was noted in 2004 (4). In 2005, MI was permitted for use in cosmetics in the United States and Europe at up to 100 ppm, representing a 27-fold increase in the permitted concentration of MI. It is unclear how soon after 2005 MI was incorporated into cosmetics as a single agent, but the first cases of allergic contact dermatitis caused by MI through cosmetic exposure were reported in 2010 (5). In that year we incorporated MI, at a patch test concentration of 0.05% aqua, into our cosmetic/face patch test series.

A general population from Thailand: incidence of common allergens with emphasis on para-phenylenediamine

Background Most studies on the prevalence of allergy to the permanent hair dye chemical para‐phenylenediamine (PPD) are reported from populations of eczema patients attending patch‐test clinics, and are assumed to be much higher than in the normal population. No data exist on incidence of senitization to PPD resulting from the use of commercial hair dye preparations over a defined time period.

Intermittent exposure to low-concentration paraphenylenediamine can be equivalent to single, higher-dose exposure.

Hair dye allergy is an important and increasingly common cause of allergic contact dermatitis. The role of repeated exposure in elicitation of allergy has not previously been extensively studied. We have therefore compared elicitation between single and intermittent exposure to paraphenylenediamine (PPD). 23 subjects known to be allergic to PPD from positive patch tests were exposed to 0.3% and 0.03% PPD, both in petrolatum and water, for 5 min at the same site every day for up to 8 D. In the same subjects, single exposures were also performed at different sites, from 5 to 40 min. Other experiments exposed rat skin to radiolabelled PPD as one‐off application or multiple exposures. There were 8 reactions in the cumulative exposure site using 0.3% PPD in aqueous solution. In 7 of these, there was an exact correlation with reaction to the cumulative time needed for repeat exposures to elicit a reaction and the time needed for a reaction to the single exposure. There were no reactions to 0.03% PPD in water or pet under either type of exposure condition. There was also a positive correlation between grade of original reaction in clinic (+++, ++, +) and appearance/intensity of elicitation reactions. In the animal study, cumulative time and single exposure time sites correlated with regards to retention of radiolabelled substance within the skin. This study therefore demonstrates for the first time that, over the time period tested, the allergenic component of PPD accumulates in the skin. Hence, intermittent exposure to lower concentrations of PPD may be equivalent to higher concentration, one‐off exposure.

Oral tolerance to contact allergens: A common occurrence? A review

Experimental and clinical oral tolerance to contact allergens has been reported sporadically, most notably in respect of nickel, and is generally assumed to be an uncommon phenomenon. There has recently been increased understanding of the immunological mechanisms inducing and maintaining oral tolerance. There are several contact allergens, including fragrance, antioxidant, and preservative chemicals, to which subjects are exposed through both cutaneous and oral routes. We examine the possibility that oral tolerance to contact allergens may be more common than previously thought. Animal models of oral tolerance to contact allergens indicate that cutaneous exposure to small, subsensitizing doses of contact allergens might negate any subsequent attempts to induce tolerance by oral administration. Extrapolating these observations to common human practises raises the possibility that application of contact allergens (fragrances, preservatives and antioxidants) in consumer products used by children could prevent or inhibit the later acquisition of specific tolerance resulting from ‘natural’ dietary exposure after weaning. Existing data on formaldehyde may conflict with this theory, though this could be explained by allergen specificity. We propose that further work in this area is needed.

Patch testing in patients treated with systemic immunosuppression and cytokine inhibitors

Background: Currently, there is little data available on the reliability of patch testing in patients taking immunosuppressive agents other than systemic corticosteroids.