title: The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals.
abstract: The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Repeated Open Application Test (ROAT) using two concentrations of isoeugenol, 0.2 and 0.05%. Seven controls without isoeugenol allergy were also included. The participants applied 3.72 +/- 1.57 (mean +/- SD) mg/cm(2) of coded isoeugenol solutions twice a day to a 3 x 3 cm(2) area on the volar aspect of the right and left arm, respectively. For each test site the applications continued until a reaction appeared or for a maximum of 28 days. The minimal criteria for a positive reaction regarded as allergic contact dermatitis was persistent erythema at the ROAT test site. All controls were negative and 16/24 (66.7%) of the included isoeugenol-sensitive subjects showed a positive ROAT to the 0.2% solution within the study period (Fisher's test, p = 0.0024). Ten of the positive patients also reacted to the 0.05% solution. The median number of days until a positive reaction to the 0.2% solution was 7 days and was 15 days for the 0.05% solution. There was a highly significant correlation between the patients' patch test threshold and the number of days until a positive ROAT. In conclusion, the time until an isoeugenol allergic individual reacts in a ROAT depends on the individual sensitivity as well as the exposure concentrations; for low concentrations of the allergen or low degree of sensitivity, the allergic contact dermatitis may develop after several weeks of exposure. Therefore, a negative ROAT after 7 days may be a false negative.
authors.affiliation: Department of Dermatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: K E
authors.initials: KE
authors.lastname: Andersen
authors.forename: J D
authors.initials: JD
authors.lastname: Johansen
authors.forename: M
authors.initials: M
authors.lastname: Bruze
authors.forename: P J
authors.initials: PJ
authors.lastname: Frosch
authors.forename: A
authors.initials: A
authors.lastname: Goossens
authors.forename: J P
authors.initials: JP
authors.lastname: Lepoittevin
authors.forename: S
authors.initials: S
authors.lastname: Rastogi
authors.forename: I
authors.initials: I
authors.lastname: White
authors.forename: T
authors.initials: T
authors.lastname: Menné
mesh_terms: D000287:Administration, Topical; D000485:Allergens / Q000009:adverse effects*; D003718:Denmark; D003877:Dermatitis, Contact / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology*; D005054:Eugenol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D010476:Perfume / Q000009:adverse effects; D013997:Time Factors
chemical_list: D000485:Allergens; D010476:Perfume; D005054:Eugenol; C036643:isoeugenol