Assessment of the elicitation response in subjects weakly sensitized to p-phenylenediamine

• Published in: British journal of dermatology (1951) Vol. 172; no. 1; pp. 138 - 144
• Main Authors: Pot, L.M., Coenraads, P.J., Goebel, C., Blömeke, B.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2015
• Subjects: Adult; Dermatitis, Allergic Contact - diagnosis; Dermatitis, Allergic Contact - etiology; Drug Hypersensitivity - diagnosis; Drug Hypersensitivity - etiology; Female; Follow-Up Studies; Hair Dyes - adverse effects; Humans; Middle Aged; Patch Tests - methods; Phenylenediamines - adverse effects; Time Factors; Young Adult
• ISSN: 0007-0963; 1365-2133; 1365-2133
• DOI: 10.1111/bjd.13142

Summary Background A 30‐min application of a hair dye product containing 2% p‐phenylenediamine (PPD) to subjects diagnostically graded +, showed that 12 of 18 reacted; eight of 18 with a true + and four of 18 with a doubtful (?+) response, whereas six of 18 did not react at all. In vitro skin‐binding experiments showed that for diagnostic patch test conditions the measured exposure level (MEL) is more than 10‐fold higher than the MEL for hair dyeing conditions. Objective To further analyse the limited elicitation response of the diagnostically + graded subjects to a PPD hair dye product, under standardized test conditions mimicking product usage, by varying exposure time and dose. Methods A hair dye model formulation containing 2% PPD, applied for 30, 45 and 60 min and a diagnostic PPD TRUE test® were applied to assess elicitation responses to increasing PPD exposure levels. Grading was performed according to International Contact Dermatitis Research Group guidelines. Results Six subjects were available for this follow‐up study. One of six subjects responded with a +  elicitation response to the hair dye model applied for 60 min. Four of the five remaining subjects elicited a + response to the PPD TRUE test® applied subsequently, while one of five responded doubtfully. Conclusions Increasing the PPD exposure time twofold – resulting in a 5–6% increase of sensitivity of this hair dye model test – or further extending the exposure time 48‐fold, was found sufficient to increase the MEL above the thresholds needed to elicit individuals with a + diagnostic PPD patch test who did not react to typical hair dye use conditions with a MEL of about 6·8 μg cm−². This analysis confirms that consideration of the MEL is a useful tool to better characterize thresholds of elicitation than consideration of the applied dose alone. What's already known about this topic? Elicitation of individuals sensitized to p‐phenylenediamine (PPD) is dose dependent: after application of a hair dye formulation containing 2% PPD for 30 min to 18 subjects weakly sensitized (+) to PPD, six (33%) did not react and four (22%) showed only a doubtful response. Experimentally derived measured exposure levels (MEL) to PPD showed that the MEL for this hair dye condition is 6·8 μg PPD cm−2, whereas a diagnostic 1% PPD–petrolatum patch test for 48 h resulted in a MEL of 205 μg PPD cm−2. What does this study add? Increasing the MEL to 16 μg PPD cm−2 – by doubling the exposure time of a 2% PPD hair dye formulation to 60 min – showed a minor increase of 5–6% in elicitation responses of the nonresponders and doubtful responders from a previous study. Applying a PPD TRUE test® indicated that a further increase in MEL (estimated to be in the region of 45 μg PPD cm−2) is associated with a major increase (four of five) in positive elicitation responses. By combining elicitation data with measured PPD exposure levels (MEL), a range of exposure conditions could be established, within which responses can be elicited in a number of subjects weakly sensitized to PPD. This confirms that exposure dose and time determine the MEL and thus the threshold of the elicitation response.