An evaluation of dose/unit area and time as key factors influencing the elicitation capacity of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in MCI/MI-allergic patients

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1-3% of patch-tested patients in European centres. The aim of the present study was to evaluate the importance of the factors--time and concentration (dose/per unit area)--in the elicitation capacity by means of a repeated open application test (ROAT) experimental design. The study was designed as a double-blind, placebo-controlled, dose-response ROAT preceded by a diagnostic patch testing. 25 subjects with confirmed MCI/MI allergy and 10 healthy, non-MCI/MI allergic control subjects were exposed to 0.025 microg/cm2 (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash-out period of at least 4 weeks, the subjects were exposed to 0.094 microg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process. It demonstrated that the elicitation threshold for MCI/MI is expected to be in the proximity of 0.025 microg/cm2 although it was not possible to establish a definitive elicitation threshold for MCI/MI in this study.     

Methylchloroisothiazolinone/methylisothiazolinone contact sensitization: diverging trends in subgroups of IVDK patients in a period of 19 years

Background. The preservative methylchloroisothiazolinone (MCI)/methylisothiazo- linone (MI) is an important allergen, and has thus been subject to regulation in some areas of exposure, mainly in cosmetics. Objectives. To examine whether a decline in sensitization prevalence and intensity of elicitation (by the patch test) can be observed, either overall, or in certain subgroups defined by causative exposures. Methods. On the basis of long-term contact allergy surveillance data collected by the Information Network of Departments of Dermatology (www.ivkd.org), 1992-2010, in the course of 171 883 consultations, the time trend of (different grades of) positive patch test reactions to MCI/MI (0.01% aqua) was examined in an age-stratified analysis. Results. The overall frequency of positive patch test reactions was 2.33% (95% confidence interval 2.26-2.4%). No significant overall trend of positive reactions or of the distribution of +, ++ and + + + reactions (p > 0.05) was observed, similarly to what was found for patients in whom cosmetics were recorded as causative exposure (p = 0.55). In contrast, in patients with occupational contact dermatitis who were < 40 years of age, a significant increase in prevalence, by 0.87 percentage points per decade, was identified (p = 0.018). Conclusions. Both applications of MCI/MI, cosmetic and industrial, should be the target of further preventive efforts.     

Patch test reactions to cosmetic allergens in 1995-1997 and 2000-2002 in Finland--a multicentre study

Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary between countries and study periods. The present survey aimed at revealing the recent trends in patch test sensitivity with cosmetic chemicals in Finland. We report a retrospective multicentre survey of patch test reactions focusing on cosmetic-related substances and comparing the test results in 1995-97 with those in 2000-02. The most striking increases in the frequency of the patch test sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P < 0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most prominent decreases were found with methylchloro/methylisothiazolinone and chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P < 0.001), respectively. The level of patch test sensitivity to methyldibromo glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An increasing tendency was also found with hair dye chemicals 4-aminophenol and toluene-2,5-diamine or toluene-2,5-diamine sulfate from 1.3% to 3.8% and from 1.4% to 5.2%, respectively, while such a tendency was not found among permanent wave chemicals. The sensitivity level of fragrance mix remained the same (6% - 7%). We conclude that surveys revealing the state of sensitivity to cosmetic chemicals should be performed periodically in different countries.     

Dose per unit area - a study of elicitation of nickel allergy

BACKGROUND: Experimental sensitization depends upon the amount of allergen per unit skin area and is largely independent of the area size. OBJECTIVES: This study aimed at testing if this also applies for elicitation of nickel allergy. PATIENTS/METHODS: 20 nickel allergic individuals were tested with a patch test and a repeated open application test (ROAT). Nickel was applied on small and large areas. The varying parameters were area, total dose and dose per unit area. RESULTS: In the patch test, at a low concentration [15 microg nickel (microg Ni)/cm(2)], there were significantly higher scores on the large area with the same dose per area as the small area. At higher concentrations of nickel, no significant differences were found. In the ROAT at low concentration (6.64 microg Ni/cm(2)), it was found that the latency period until a reaction appeared was significantly shorter on the large area compared to the small area. It was also found that the ROAT threshold (per application) was lower than the patch test threshold. CONCLUSION: For elicitation of nickel allergy, the size of the exposed area and therefore the total amount of applied nickel, influence the elicitation reaction at some concentrations, even though the same dose per unit area is applied.     

Use tests: ROAT (repeated open application test)/PUT (provocative use test): an overview

As one step in defining the clinical relevance of exposure to an allergen identified with patch testing, use tests (provocative use test (PUT), and repeated open application test (ROAT)) have been used. In 1/2 of the cases of seemingly reliable patch tests, use tests are negative, suggesting that the patient's biologic threshold of response had not been reached with open application dosing. Dramatic differences exist in regional skin reactivity and percutaneous penetration. Negative results of use tests on normal skin may become positive on diseased skin. To refine this assay further, more controlled observations and analysis of reaction differences between normal and damaged skin, and among regional anatomic sites might be performed. In addition, we require a standardized measurement for the results. Use testing has significant potential in refinement of the evidence-based diagnosis of clinical relevance. However, for general validation, we should fill the deficiencies described above.