Position statement: The need for EU legislation to require disclosure and labelling of the composition of medical devices.

BACKGROUND: In recent years, skin reactions secondary to the use of medical devices (MD), such as allergic contact dermatitis have increasingly been observed (e.g. to continuous blood sugar monitoring systems, insulin pumps, wound dressings, medical gloves, etc.): this is regarded as a developing epidemic. Lack of labelling of the composition of MD, as well as frequent lack of cooperation of manufacturers to disclose this relevant information, even when contacted by the clinician for the individual case of an established adverse reaction, significantly impede patient care. OBJECTIVES: To advocate for full ingredient labelling in the implementation of EU regulation for MD. METHODS: This position paper reviews the scientific literature, the current regulatory framework adopted for MD to date, and the likely impact, including some costs data in case of the absence of such labelling. RESULTS: Efforts made by several scientific teams, who are trying to identify the culprit of such adverse effects, either via asking for cooperation from companies, or using costly chemical analyses of MD, can only partly, and with considerable delay, compensate for the absence of meaningful information on the composition of MD; hence, patient management is compromised. Indeed, without knowing the chemical substances present, physicians are unable to inform patients about which substances they should avoid, and which alternative MD may be suitable/tolerated. CONCLUSION: There is an urgent need for full and accurate labelling of the chemical composition of MD in contact with the human body.

Atopic dermatitis at preschool age and contact allergy in adolescence: a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is characterized by an impaired skin barrier, which can allow enhanced penetration of allergens. It is not clear whether AD influences the risk of developing contact allergy. OBJECTIVES: To examine the association between AD at preschool age and contact allergy at 16 years of age. METHODS: At 16 years of age, 2215 adolescents from the population-based cohort BAMSE were included. These adolescents had been followed with repeated questionnaires regarding AD throughout childhood, and contact allergy was assessed by skin patch test at 16 years. RESULTS: AD at preschool age was associated with contact allergy to at least one of the tested substances at 16 years of age among boys [adjusted odds ratio (OR) 1·51, 95% confidence interval (CI) 1·03-2·20] but not among girls (adjusted OR 0·77, 95% CI 0·54-1·10). AD at preschool age was not associated with contact allergy to nickel in either boys or girls. In contrast, AD at preschool age was associated with contact allergy to fragrance mix I (adjusted OR 3·10, 95% CI 1·66-5·80). This association was observed especially for AD at preschool age in combination with IgE sensitization to airborne or food allergens (adjusted OR 3·80, 95% CI 1·67-8·61). CONCLUSIONS: The results suggest that AD in early childhood may be associated with contact allergy to fragrances, but not to nickel, in adolescence.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

Isothiocyanates are important as haptens in contact allergy to chloroprene rubber.

BACKGROUND: Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. OBJECTIVES: To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. METHODS: Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. RESULTS: All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm-2 . At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. CONCLUSIONS: Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.

Methylisothiazolinone in rinse-off products causes allergic contact dermatitis: a repeated open-application study.

BACKGROUND: In recent years, the prevalence of contact allergy to the preservative methylisothiazolinone (MI) has increased dramatically. Cosmetic products are one of the major sources of exposure. OBJECTIVES: To examine whether allowed concentrations of MI in cosmetic rinse-off products have the potential to cause allergic contact dermatitis. METHODS: Nineteen MI-allergic subjects and 19 controls without MI allergy applied two liquid hand soaps five times per day on areas of 5 × 10 cm(2) on the ventral side of their forearms. One soap contained 100 ppm MI, the maximum allowed concentration in cosmetics, and was used by 10 allergic subjects and all controls. Another liquid soap with 50 ppm MI was used by nine allergic subjects. As the negative control, all subjects used a similar soap that did not contain MI. The repeated open applications proceeded until a positive reaction occurred or up to 21 days. The study was conducted in a randomized and blinded fashion. RESULTS: Ten out of 10 MI-allergic subjects developed positive reactions to the soap with 100 ppm and seven out of nine reacted to the 50 ppm soap, while none of the 19 controls had a positive reaction during 21 days of application. No reactivity was seen to the soap without MI. The difference in reactivity to MI between MI-allergic subjects and controls was statistically significant (Fisher's exact test, P ˂ 0.0001). CONCLUSIONS: Rinse-off products preserved with 50 ppm MI or more are not safe for consumers. No safe level has yet been identified.

Fluticasone propionate: a rare contact sensitizer.

Fluticasone propionate is the first of a new generation of fluorinated corticosteroids that have been synthesized with a view to separating local activity from undesirable side effects. In recent years, contact allergy to the newer topical corticosteroids has received increasing attention. The results of patch testing with fluticasone propionate, even in patients with a known contact allergy to corticosteroids, argue for a low sensitization and cross-sensitization potential.

Reactions to corticosteroids: some new aspects regarding cross-sensitivity.

Patch test results obtained with corticosteroid allergic patients tested with a large corticosteroid series validated the earlier classification of corticosteroid molecules in four groups of cross-reacting molecules: i.e., group A (hydrocortisone type), group B (acetonides), group C (betamethasone type-non esterified) and group D (esters). The latter group can now be subclassified into 2 groups, i.e., group D1 (halogenated and with C16 substitution) and group D2 (the "labile" prodrug esters without the latter characteristics).

Contact allergy to imidazoles used as antimycotic agents.

The present article reviews the literature (up to 1994) on contact sensitivity to imidazoles and presents the results obtained from 15 patients observed at the Contact Allergy Unit in Leuven. The frequency as well as the cross-reaction patterns described are analyzed. Although allergic contact reactions may have been missed in the past (mainly because of problems with the correct choice of vehicle for patch testing), they seem to be relatively infrequent in view of their widespread use. The imidazole derivatives most frequently reported to be allergens are miconazole, econazole, tioconazole, and isoconazole. As far as cross-reactivity is concerned, statistically significant associations were found in the patient data between miconazole, econazole, and isoconazole; between sulconazole, miconazole, and econazole; and also between isoconazole and tioconazole. Patients sensitive to phenylethyl imidazoles (except ketoconazole) needing antimycotic therapy should be advised to use ketoconazole, clotrimazole, bifonazole, or, perhaps, the new flutrimazole. Clearly, non-imidazole antifungals can also be used.