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.

The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.

BACKGROUND: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. OBJECTIVE: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. METHODS: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. RESULTS: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. CONCLUSION: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.

Factors associated with combined hand and foot eczema.

BACKGROUND: As for hand eczema, the aetiology of foot eczema is multifactorial and not very well understood. The aim of the present study was to identify factors associated with foot eczema in a cohort of hand eczema patients being classified into different subgroups. METHODS: Associations between foot and hand eczema were studied in a cross-sectional design in a cohort of hand eczema patients. Consecutive patients were recruited from nine different European Centres during the period October 2011-September 2012. Data on demographic factors, presence of foot eczema, hand eczema duration and severity, and whether the hand eczema was work-related or not were available, as well as patch-test results. RESULTS: Of a total of 427 hand eczema patients identified, information on foot eczema was available in 419 patients who were included in the present study. A total of 125 patients (29.8%) had concomitant foot and hand eczema. It was found more often in association with hyperkeratotic hand eczema (P = 0.007) and was less often associated with irritant hand eczema (P < 0.001). However, foot eczema was nevertheless found in 18% of patient with irritant hand eczema and in 25% of patients with occupational hand eczema. Combined foot and hand eczema was associated with more severe and long-standing hand eczema (P < 0.001 and P = 0.004, respectively). Contact allergy was found in 51.8% with no difference between patients with combined foot and hand eczema and patients with hand eczema only. CONCLUSION: Occurrence of combined foot and hand eczema is a common finding and not restricted to endogenous hand eczema.

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.

Classification of hand eczema.

BACKGROUND: Classification of hand eczema (HE) is mandatory in epidemiological and clinical studies, and also important in clinical work. OBJECTIVES: The aim was to test a recently proposed classification system of HE in clinical practice in a prospective multicentre study. METHODS: Patients were recruited from nine different tertiary referral centres. All patients underwent examination by specialists in dermatology and were checked using relevant allergy testing. Patients were classified into one of the six diagnostic subgroups of HE: allergic contact dermatitis, irritant contact dermatitis, atopic HE, protein contact dermatitis/contact urticaria, hyperkeratotic endogenous eczema and vesicular endogenous eczema, respectively. An additional diagnosis was given if symptoms indicated that factors additional to the main diagnosis were of importance for the disease. RESULTS: Four hundred and twenty-seven patients were included, 379 (89%) of the patients could be classified directly into one of the six diagnostic subgroups, with irritant and allergic contact dermatitis comprising 249 patients (58%). For 32 (7%) more than one of the six diagnostic subgroups had been formulated as a main diagnosis, and 16 (4%) could not be classified. 38% had one additional diagnosis and 26% had two or more additional diagnoses. Eczema on feet was found in 30% of the patients, statistically significantly more frequently associated with hyperkeratotic and vesicular endogenous eczema. CONCLUSION: We find that the classification system investigated in the present study was useful, being able to give an appropriate main diagnosis for 89% of HE patients, and for another 7% when using two main diagnoses. The fact that more than half of the patients had one or more additional diagnoses illustrates that HE is a multifactorial disease.

Long-term follow-up study of occupational hand eczema.

BACKGROUND: Long-term follow-up studies on the prognosis and consequences of occupational hand eczema (OHE) and the prognostic risk factors for persistent OHE are sparse. OBJECTIVES: To determine the medical and occupational outcome after a follow-up of 7-14 years in 605 patients diagnosed with OHE and to identify the prognostic risk factors for the continuation of hand eczema. METHODS: Patients examined at the Finnish Institute of Occupational Health in 1994-2001 completed a follow-up questionnaire 7-14 years after diagnosis. RESULTS: The hand eczema had healed (no eczema during the last year) in 40% of patients with OHE. The duration of hand eczema before diagnosis was strongly associated with the continuation of eczema. Age, sex and diagnosis (allergic or irritant contact dermatitis) were not associated with the prognosis, but skin atopy, and especially respiratory atopy, were correlated with the continuation of hand eczema. Contact allergies in general were not risk factors for persistent OHE, but the presence of a work-related chromate allergy was associated with poor healing. A total of 34% of patients had changed their occupation due to OHE, and their long-term prognosis was better than those who had not. The hand eczema of patients originally in food-related occupations continued on an unfavourable course. CONCLUSIONS: In the logistic model, risk factors for the continuation of OHE were a long duration of hand eczema before diagnosis, respiratory atopy, skin atopy, and continuation in the same occupation. Those who ended up changing occupation due to their OHE had a better medical and economic prognosis.

Cardio-facio-cutaneous syndrome: three additional cases and review of the literature.

We report on 3 patients with the cardio-facio-cutaneous (CFC) syndrome. Each of them was a sporadic case in the family. The severity of the psychomotor retardation varied from mild to severe. Skin manifestations were often minimal, but each patient had abnormally curly and brittle hair. A skin biopsy from one of the patients showed vellus hair cysts filled with keratin, and the hair follicles were surrounded by unusually thick fibrotic sheaths.

Improvement of skin barrier function during treatment of atopic dermatitis.

BACKGROUND: Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone. OBJECTIVE: The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis. METHODS: Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and TEWL at intervals of 1 to 3 days. Percutaneous absorption of hydrocortisone was measured at entry and during treatment. RESULTS: At entry, both TEWL and percutaneous absorption of hydrocortisone were elevated. Four to six days later, a significant decline was observed in both variables, indicating rapid improvement in skin barrier function. Individual changes in TEWL correlated with the changes in the systemic absorption of hydrocortisone. CONCLUSION: TEWL reflects changes in the systemic absorption of topical hydrocortisone during treatment of atopic dermatitis.

Quantifying systemic absorption of topical hydrocortisone in erythroderma.

The systemic absorption of topical hydrocortisone (HC) was quantified in seven patients with erythroderma, using the ratio of the areas under the curves for plasma concentration vs. time, following topical and intravenous administration. Over a period of 24 h, 19-93 mg of HC was absorbed systemically, corresponding to 4-19% of the total topical dose of 500 mg. Thus, topical HC therapy of erythroderma is accompanied by a pharmacologically significant systemic dose.

Bone mineral density in patients with atopic dermatitis.

With the aim of evaluating the systemic effect of glucocorticoids (GCs), we measured bone mineral density (BMD) in 29 adult patients with chronic atopic dermatitis. BMD was measured in the lumbar spine and in the left femoral neck using dual-energy X-ray absorptiometry (DEXA). In the right calcaneus, BMD was measured using broad-spectrum ultrasound attenuation (BUA). For BMD, the patients with dermatitis did not differ from healthy controls. We did not find any statistically significant correlation between BMD and single risk factors, such as the barrier function of the skin (P = 0.08), the duration of the dermatitis (P = 0.58), and the use of oral GCs (P = 0.27) and potent topical GCs (P = 0.10). However, selected patients with severe disease, needing topical GCs of higher potency than hydrocortisone (HC), had lower values for lumbar BMD than the patients who had not used these preparations (-1.0 vs. +0.1 SD; P = 0.026). The lower lumbar BMD in this group could be explained by a long-term systemic effect of GCs.

Transepidermal water loss and absorption of hydrocortisone in widespread dermatitis.

Percutaneous absorption of hydrocortisone was measured in three children and six adults with widespread dermatitis, after the application of 1% hydrocortisone cream. Before application of the cream, the transepidermal water loss (TEWL) was measured on six skin areas. A highly significant correlation was found between the post-application rise in plasma cortisol level and the mean transepidermal water loss. Thus, measurement of TEWL affords a simple, non-invasive method for assessing the systemic effect of hydrocortisone applied to widespread dermatitis.

Pharmacokinetics of topical hydrocortisone at plasma level after applications once or twice daily in patients with widespread dermatitis.

Percutaneous absorption of hydrocortisone was measured by determining plasma cortisol during dexamethasone suppression in 26 patients with widespread atopic dermatitis. The first and second days of treatment with applications of 1% hydrocortisone cream twice daily were studied separately in two groups of six patients. Plasma cortisol levels rose after the first two applications, reaching a maximum in 24 h. The levels then began to fall, indicating possible restoration of the skin barrier. In two other groups of seven patients, the second application was made with a cream base alone. Two types of cream base were studied, one with 60% water and the other with 30% water. With the base containing 30% water, a brief increment was seen after 2 h. On the basis of this pharmacokinetic study, treatment of acute dermatitis could be intensified by applying hydrocortisone cream twice a day on the first day, but from the second day onward one application a day seems to be sufficient.

Formaldehyde-negative allergic contact dermatitis from melamine-formaldehyde resin.

Melamine-formaldehyde resin (MFR) is used as a textile finish, in tableware, in surface coatings, and in glues in the furniture and wood industry. MFR is considered to be an infrequent sensitizer. Contact allergy to MFR is often combined with formaldehyde allergy. Patients allergic to textile finish often react to MFR, although other finishes are nowadays more commonly used. Besides allergy to textile finish, allergic contact dermatitis from MFR has been described in workers in composite production and in an orthopaedic plaster technician. To our knowledge, there are no previous reports of contact allergy in the plywood industry from MFR. We describe 3 cases of occupational allergic contact dermatitis from MFR without contact allergy to formaldehyde, 1 in the plywood industry, 1 in the production of melamine-laminated chipboard and 1 in laboratory work.

A multicenter study of patch test reactions with dental screening series.

BACKGROUND: Dental products contain many allergens, and may cause problems both for patients undergoing dental treatment and for dental personnel because of occupational exposure. Individual patch test clinics may not study sufficient numbers of patients to collect reliable data on uncommon allergens. OBJECTIVE: To collect information on dental allergens based on a multicenter study. MATERIALS AND METHODS: The Finnish Contact Dermatitis Group tested more than 4,000 patients (for most allergens, 2,300 to 2,600 patients) with dental screening series. Conventional patch testing was performed. The total number and percentage of irritant (scored as irritant [IR] or doubtful [?]) and allergic (scored as +, ++, or +++) patch test reactions, respectively, were calculated, as well as the highest and lowest percentage of allergic patch test reactions recorded by the different patch test clinics. A reaction index (RI) was calculated, giving information on the irritancy of the patch test substances. RESULTS: The most frequent allergic patch test reactions were caused by nickel (14.6%), ammoniated mercury (13%), mercury (10.3%), gold (7.7%), benzoic acid (4.3%), palladium (4.2%) and cobalt (4.1%). 2-hydroxyethyl methacrylate (2.8%) provoked most of the reactions caused by (meth)acrylates. Menthol, peppermint oil, ammonium tetrachloroplatinate, and amalgam alloying metals provoked no (neither allergic nor irritant) patch test reactions. CONCLUSION: Patch testing with allergens in the dental screening series, including (meth)acrylates and mercury, needs to be performed to detect contact allergy to dental products.