Allergic contact dermatitis caused by hydroperoxides of limonene and dose‐response relationship—A repeated open application test (ROAT) study

• Published in: Contact dermatitis Vol. 80; no. 4; pp. 208 - 216
• Main Authors: Bennike, Niels H., Palangi, Lina, Christensson, Johanna Bråred, Nilsson, Ulrika, Zachariae, Claus, Johansen, Jeanne D., Hagvall, Lina
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2019; Wiley Subscription Services, Inc
• Subjects: Allergens; allergic contact dermatitis; Allergies; clinical relevance; contact allergy; Contact dermatitis; Dermatitis; dose-response relationship; Eczema; fragrance substance; Limonene; limonene hydroperoxides; oxidized limonene; ROAT; Statistical analysis; contact allergy; allergic contact dermatitis; ROAT; fragrance substance; dose-response relationship; limonene hydroperoxides; oxidized limonene; clinical relevance
• ISSN: 0105-1873; 1600-0536; 1600-0536
• DOI: 10.1111/cod.13168

Background Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim‐OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported. Objectives To determine the clinical relevance, elicitation threshold and dose‐response relationship of Lim‐OOHs in individuals with a positive or doubtful patch test reaction to standard Lim‐OOHs 0.3% pet. Methods A multicentre 3‐week double‐blind vehicle‐controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim‐OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim‐OOHs of 3.0, 0.99 and 0.33 μg/cm2, was performed. Results Among 11 subjects allergic to Lim‐OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim‐OOHs, two (15%) had positive ROAT reactions to the highest Lim‐OOH dose applied (P = 0.36 as compared with controls). Conclusions Contact allergy to Lim‐OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim‐OOHs 0.3% pet. can be of clinical relevance.