Contact allergy to common ingredients in hair dyes

Background. It is widely accepted that there is a molecular weight (MW) cut‐off of 500, such that single chemicals with MWs higher than 500 cannot be skin sensitizers. If true, this could serve as a useful principle for designing non‐sensitizing chemicals. Objectives. To assess whether the 500 MW cut‐off is a myth or a reality. Methods. A database of 699 chemicals tested for skin sensitization in guinea pigs or mice was analysed to establish the number of tested chemicals with MW > 500, and to establish whether any of these were sensitizers. Results. Only 13 (2%) of the 699 chemicals in the database have MW > 500. Of the 13 tested compounds with MW > 500 in the database, five are sensitizers and eight are non‐sensitizers. Conclusions. The 500 MW cut‐off for skin sensitization is a myth, probably derived from the widespread misconception that ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potency. The scarcity of sensitizers with MW > 500 simply reflects the general scarcity of chemicals with MW > 500.     

Patch testing with 2.0% (0.60 mg/cm2) formaldehyde instead of 1.0% (0.30 mg/cm2) detects significantly more contact allergy

Background. The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. Objectives. To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co‐reactivity with quaternium‐15. Materials and methods. In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm²) and 1.0% (wt/vol) (0.30 mg/cm²) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. Results. Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium‐15‐positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. Conclusion. On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.     

Photopatch testing: recommendations for a European photopatch test baseline series

In order to establish a consensus recommendation for performing photopatch testing, a photopatch test taskforce group was established under the joint umbrella of the European Society for Contact Dermatitis and the European Society for Photodermatology in 2000. After proposing the most adequate methodology in 2004 and completing a European multicentre photopatch test study in 2011, this taskforce is recommending a list of photoallergens that should form part of a baseline series for photopatch testing in Europe. It contains mainly ultraviolet filters and drugs, mostly non‐steroidal anti‐inflammatory drugs. The choice of chemicals was based on the results of a recent multicentre study, previous published cases of photoallergy, and use of the substances in the European market. It is suggested that an extended list of photoallergens should be photopatch tested in selected cases, along with patients' own products. Two contact allergens, cinnamyl alcohol and decyl glucoside, should be simultaneously patch tested in order to clarify photopatch and patch test reactions, respectively, to ketoprofen and methylene bis‐benzotriazolyl tetramethylbutylphenol (Tinosorb M?).     

Do ‘cinnamon‐sensitive’ patients react to cinnamate UV filters?

Background:  Use of sunscreens has increased dramatically worldwide, and some sunscreen chemicals may be allergens. Ultraviolet (UV) filters are added to various cosmetic products. Cinnamate UV filters are structurally related to cinnamon-related fragrances.
Objective:  The purpose of this study was to determine if 'cinnamon-sensitive' patients show positive photopatch tests to cinnamate UV filters and, therefore, should avoid these UV filters.
Method:  We photopatch tested cinnamon-sensitive patients ( n  = 18) with cinnamon, cinnamon-related fragrances, Myroxylon pereirae , and two cinnamate UV filters.
Results:  No positive photopatch test to cinnamate UV filters was found (95% confidence interval 0–13%).
Discussion:  The risk of developing unwanted allergic contact dermatitis because of cinnamate UV filters in cinnamon-sensitive patients seems to be low, but our study population was small. Therefore, we recommend cinnamon-sensitive patients to perform a use test, for example the repeated open application test, before using cosmetic products containing cinnamate UV filters. In addition, physicians and patients should be aware that many sunscreens contain (cinnamon-related) fragrances and could, therefore, elicit allergic contact dermatitis in cinnamon-sensitive patients, independently from other potential sensitizing components of the sunscreen.     

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.     

Allergic contact dermatitis to nickel: modified in vitro test protocols for better detection of allergen-specific response

To date, no in vitro test is suitable for routine diagnosis of contact allergy. The aim of our study was to establish improved in vitro test protocol for the detection of antigen-specific responses of lymphocytes from patients with allergic contact dermatitis to nickel (Ni-ACD). Blood leucocytes from 14 Ni-ACD patients and 14 controls were cultured in the presence of 'cytokine cocktails' skewing lymphocytes towards 'type 1' [interferon-gamma (IFN-gamma)-secreting] or 'type 2' [interleukin (IL)-5 and IL-13-secreting] phenotypes. The cocktails consisted of IL-7 and, respectively, either IL-12 or IL-4. Cell responses to nickel were measured with enzyme-linked immunospot assay (ELISpot), enzyme-linked immunosorbent assay (ELISA), and lymphocyte proliferation test (LPT). Significant differences between patients with Ni-ACD and controls were found for the 'type 2' cytokines IL-13 and IL-5, with further increase of allergen-specific responses occurring when cultures were supplemented with IL-7 and IL-4. No significant differences were found for IFN-gamma. The best correlate to clinical diagnosis was LPT with 'type 2' skewing (r= 0.739, P < 0.001), followed by IL-13 ELISpot with 'type 2' skewing (r= 0.654, P < 0.001). The non-radioactive method that correlated best with LPT was IL-2 ELISpot (r= 0.809, P < 0.001). Overall, we conclude that combining ELISpot assay with proposed modifications of culture conditions improves detection of specific lymphocyte responses in contact allergy to nickel.