Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept

The first step in the development of skin sensitisation to a chemical, and in the elicitation offurther allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after pene-trating into the epidermis. The so-formed antigenic adduct is then recognised by the immunesystem as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation ofnatural terpenes are believed to form antigens through radical-mediated mechanisms, althoughthis has not yet been established. So far,in vitroinvestigations on reactive radical intermediatesderived from these skin sensitisers have been conducted in solution, yet with experimental condi-tions being far away from real-life sensitisation. Herein, we report for the first time, the potentialuse of EPR spin-trapping to study thein situgeneration of free radicals derived from cumenehydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model, thus much closerto what may happenin vivo. Among the undesirable effects associated with dermal exposure toCumOOH, it is described to cause allergic and irritant dermatitis, being reported as a significantsensitiser. We considered exploiting the usage of spin-trap DEPMPO as an extensive view of allsort of radicals derived from CumOOH were observed all at once in solution. We showed that inthe EpiskinTMRHE model, both by incubating in the assay medium and by topical application,carbon radicals are mainly formed by redox reactions suggesting the key role of CumOOH-derived carbon radicals in the antigen formation process

Activation of linalool by myeloperoxidase? 28th Meeting of the European Research Group on Experimental Contact Dermatitis, Darmstadt, Germany

International audienc

Understanding the skin sensitization capacity of oxidized fragrances: study in an epidermal skin environment. 77th Annual Meeting of the Society of Investigative Dermatology, Chicago, États-Unis

International audienc

Formation of radicals from endoperoxide ascaridole in a 3D epidermis model and activation of the innate immune response. 77th Annual Meeting of the Society of Investigative Dermatology, Chicago, États-Unis

International audienc

In Situ Alkylation of Reconstructed Human Epidermis by Methyl Methanesulfonate: A Quantitative HRMAS NMR Chemical Reactivity Mapping

International audienc

Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix

The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral((R))), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history - certain and none - values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool

Disease burden and treatment history among adults with atopic dermatitis receiving systemic therapy: baseline characteristics of participants on the EUROSTAD prospective observational study

Background: Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions. Methods: The prospective, observational EUROSTAD study enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics. Results: A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean [standard deviation] disease severity/burden measures were high: Investigator's Global Assessment (3.1 [0.8]), Eczema Area and Severity Index (16.2 [10.9]), Peak Pruritus Numerical Rating Scale (5.5 [2.5]), sleep impairment Visual Analog Scale (49.8 [31.6]) scores, and time lost from work (4.1 [13.7] days/year) or usual activities (16.8 [38.7] days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale. Conclusions: Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies

How are patients with chronic urticaria interested in using information and communication technologies to guide their healthcare? A UCARE study

Background: Patients with chronic urticaria (CU) are increasingly using information and communication technologies (ICTs) to manage their health. What CU patients expect from ICTs and which ICTs they prefer remains unknown. We assessed why CU patients use ICTs, which ones they prefer, and what drives their expectations and choices. Methods: In this cross-sectional study, 1841 patients across 17 countries were recruited at UCAREs (Urticaria Centers of Reference and Excellence). Patients with CU who were >12 years old completed a 23-item questionnaire. Results: Most patients were interested in receiving disease information (87.3%), asking physicians about CU (84.1%), and communicating with other patients through ICTs (65.6%). For receiving disease information, patients preferred one-to-one and one-to-many ICTs, especially web browsers. One-to-one ICTs were also the ICTs of choice for asking physicians about urticaria and for communicating with other patients, and e-mail and WhatsApp were the preferred ICTs, respectively. Many-to-many ICTs such as Facebook, Instagram, LinkedIn, and Twitter were least preferred for all 3 purposes. Living in rural areas and higher education were linked to higher odds of being interested in receiving disease information, asking physicians, and communicating with patients through ICTs. Conclusions: Most patients and especially patients with higher education who live in rural areas are interested in using ICTs for their healthcare, but prefer different ICTs for different purposes, ie, web browsers for obtaining information, e-mail for asking physicians, and WhatsApp for communicating with other patients. Our findings may help to improve ICTs for CU