The significance of dose for the patch test reaction

The dose is decisive for the patch test response provided that the test technique and the occlusion time are constant.1 Since decades the recommended occlusion time is 48 h2, 3 and recently a petrolatum dose of 20 mg (40 mg/cm2) was recommended.3, 4 This study was initiated to elucidate the significance of the petrolatum dose for the patch test results. Adult dermatitis patients with suspected allergic contact dermatitis were routinely tested with the Swedish baseline series5 and an additional petrolatum preparation with methyldibromo glutaronitrile at 1.0% wt/wt6 prepared at our laboratory. The Finn Chamber technique (diameter 8 mm) was used with 20 mg petrolatum preparation in each chamber.3, 4 The chambers were applied on the upper back and secured with Scanpor tape. The patches were removed after 48 h and the test was read on day 3 or day 4 according to ICDRG.2, 3 A doubtful (40 patients) or a weak positive (7 patients) reaction to the petrolatum preparation of either Myroxolon pereirae, fragrance mix I or methyldibromo glutaronitrile at 1.0% was demonstrated in 47 patients participating in the study. Additional patch testing was performed the same day with a set of three Finn chambers filled with 40, 20, and 10 mg of the respective sensitizer. These additional tests were again occluded for 48 h and read on day 3 or day 4. McNemar test, two-sided, was used for pair-wise comparisons of weak positive reactions for the three amounts of petrolatum preparation. The study was approved by the Regional Ethical Review Board, Lund Sweden, Dnr 2020/02190. The results are shown in Figure 1. Repeating the same dose (20 mg) meant that 34% (16/47) of all patients got the same degree of response as before. Now 15% (6/40) of doubtful reactors tested positively. With the higher and lower petrolatum amounts (40 and 10 mg), the corresponding figures for positive reactions were 25% (10/40) and 10% (4/40), respectively. For the seven patients with an initially weak positive reaction, the rates of positive reactions with different amounts of petrolatum preparations (40, 20, 10 mg) were 57% (4/7), 29% (2/7), and 14% (1/7), respectively. Statistically, there were significant differences between 40 and 20 mg as well as between 40 and 10 mg (p = 0.031 and 0.0039, respectively). To increase the possibility of detecting a difference in patch test response depending on the petrolatum preparation amount, we chose patch test reactions around the threshold of a positive reaction; that is, doubtful reactions with only erythema on the patch test area or erythema with infiltration not covering the whole test area and weak positive reactions with only erythema and infiltration covering the whole test area. The chosen amounts of petrolatum preparation were realistic based on a previous investigation.7 The three sensitizers were chosen as the routine patch testing with these at our department frequently results in many reactions around the threshold between doubtful and weak positive reactions. Expectedly, this study demonstrates that there are differences in test response depending on the amount of petrolatum preparation with a sensitizer applied on the back (Figure 1). Significantly, more contact allergy in this study was detected with the 40 mg petrolatum preparations. However, petrolatum doses from 25 mg (50 mg/cm2 and higher give too many reactions with a major spreading outside the test area4 why 20 mg (40 mg/cm2) is recommended.3, 4 This study also demonstrates that doubtful reactions must not automatically be regarded as irritant reactions but may represent weak contact allergic reactions not fulfilling the minimum requirements to be classified as allergic reactions. Magnus Bruze: Conceptualization; investigation; writing – original draft; methodology; formal analysis. Inese Hauksson: Investigation; writing – review and editing; data curation. Marléne Isaksson: Investigation; writing – review and editing; data curation. Cecilia Svedman: Investigation; writing – review and editing; data curation. Magnus Bruze is a member of the expert panel for fragrance safety - http://fragrancesafetypanel.org/. Marléne Isaksson has worked as consultant for IFRA, International Fragrance Association. Cecilia Svedman participates in the IDEA project sponsored by the International Fragrance Association (IFRA).