Chronic hand eczema in Europe: Patient experiences and perspectives (CHEPEP) in qualitative interviews.

BACKGROUND: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. OBJECTIVES: To explore perspectives of people with lived experience on CHE-related problems, wishes and goals. METHODS: Following a qualitative approach, we conducted topic-guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. RESULTS: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. CONCLUSIONS: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions.

Validation of questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix II: the EDEN Fragrance Study.

BACKGROUND: In a European study on contact allergy in the general population, it has been hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure and thereafter subsequent avoidance of scented products implied a diagnosis of allergic contact dermatitis. OBJECTIVES: The primary aim of this study was to validate this hypothesis/algorithm. The secondary aim was to investigate whether there was any association between the outcome of the recent repeated open application test (ROAT) and the patch test reactivity. METHODS: One hundred nine subjects with and without contact allergy to fragrance mix II (FM II) were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. RESULTS: Twenty-four positive ROAT reactions were noted in total including 20 of those 32 with contact allergy to FM II. None of the volunteers reacted to the vehicle (P < 0.001). More individuals with a positive algorithm had positive ROATs when compared with those with a negative algorithm. However, the difference was not statistically significant (P = 0.12). The lower the patch test concentration eliciting a positive test reaction, the more likely was a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. CONCLUSIONS: The algorithm used in this study was not validated but it was indicated in this ROAT setup. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period.

Protocol for the development of a core domain set for hand eczema trials.

BACKGROUND: Clinical hand eczema trials measure a variety of outcome domains to determine the success of interventions. This considerably limits the comparability and overall confidence in the study results, and thereby the strength of recommendations for clinical practice. OBJECTIVES: The Hand Eczema Core Outcome Set (HECOS) initiative aims to develop a core outcome set (COS) for the standardized evaluation of interventions in future hand eczema trials and reviews. This COS will define the minimum that should be measured and reported in controlled and randomized-controlled trials of therapeutic hand eczema interventions. The objective of this protocol is to specify the methods to develop a core domain set. METHODS: In Phase 1, a list of candidate domains will be derived from a systematic literature review concerning previously measured outcomes in hand eczema trials, from qualitative patient interviews and from expert interviews. In Phase 2, a consensus study about core domains will be conducted by an online 3-round Delphi survey and a face-to-face meeting, applying predefined consensus criteria. HECOS involves hand eczema and methods experts as well as patients and further stakeholders with an interest in the initiative. OUTLOOK: When a set of core domains has been defined, HECOS is going to identify appropriate outcome measurement instruments in a development process that will be detailed in another protocol. The COS will considerably enhance the methodological quality, comparability and usefulness of hand eczema trials for clinical decision-making and the development of new therapeutic options for hand eczema, and also reduce the effort of planning, conducting, and reporting individual hand eczema studies, reviews and meta-analyses.

Validation of the Dutch Quality of Life in Hand Eczema Questionnaire (QOLHEQ).

BACKGROUND: Measurement instruments should be validated for use in the population for which they are intended. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) has been developed to measure impairment of health-related quality of life in patients with hand eczema. OBJECTIVES: To assess validity, reproducibility, responsiveness and interpretability of the Dutch version of the QOLHEQ. METHODS: This was a prospective validation study in adult patients with hand eczema. At three time points (T0 , baseline; T1 , after 1-3 days; T2 , after 4-12 weeks), data from the QOLHEQ and multiple reference instruments were collected. Scale structure was assessed using item response theory analysis and structural equation modelling (SEM). Single-score validity and responsiveness were tested with hypotheses on correlations with reference instruments. Concerning reproducibility, intraclass correlation coefficients (ICCagreement ) and standard error of agreement (SEMagreement ) were checked. Regarding interpretability, bands for severity of quality-of-life impairment were proposed. Also, smallest detectable change (SDC) and minimally important change (MIC) were determined. RESULTS: At T0 , 300 individuals participated in the study (54% were male, mean age 45 years). Rescoring of the scale structure fitted the Rasch model and the SEM. The ICCagreement was 0·91 (95% confidence interval 0·85-0·94) and the SEMagreement was 5·2 points. Of the a priori formulated hypotheses, 80% (single-score validity) and 64% (change scores for responsiveness) were confirmed. The SDC was 14·4 points and the MIC was 11·5 points. CONCLUSIONS: The Dutch version of the QOLHEQ has a good structural validity and reproducibility and has a high single-score validity and moderate responsiveness. An improvement of ≥ 15 points should be regarded as a real, important change within the Dutch population. What's already known about this topic? The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) measures impairment of health-related quality of life (HRQoL) in patients with hand eczema. The QOLHEQ was validated in Germany and Japan, but the validity and interpretability of the Dutch version are unknown. What does this study add? This study shows that the Dutch QOLHEQ is a valid instrument to measure HRQoL impairment in Dutch patients with hand eczema, demonstrating good reliability and moderate responsiveness. Methods of item response theory are applied to assess and refine the scoring structure. Severity gradings to interpret single and change scores, specifically in Dutch patients, are proposed. What are the clinical implications of this work? The Dutch QOLHEQ can now be used to measure HRQoL impairment in Dutch patients with hand eczema.

Validation of a questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix I.

BACKGROUND: In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. OBJECTIVES: The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. METHODS: In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. RESULTS: Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P < 0·001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. CONCLUSIONS: The algorithm used in this study was not substantiated in this ROAT set-up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic? To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add? This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT. What are the clinical implications of this work? Further refinement of the questions is required in order to diagnose allergic contact dermatitis from fragrances based on a questionnaire.

[Epidemiology of hand eczema in Germany : A retrospective view of the past 10 years of hand eczema research in Germany]. / Epidemiologie des Handekzems in Deutschland : Ein Rückblick auf die letzten 10 Jahre Handekzemforschung in Deutschland.

BACKGROUND: There is a lack of epidemiological data describing patterns of hand eczema with reference to the general German population. OBJECTIVE: Epidemiological data were extracted from all internationally published clinical studies which investigated hand eczema in Germany. MATERIAL AND METHODS: A search was carried out for all clinical studies performed in Germany in the previous 10 years involving hand eczema patients. Inclusion criteria were that at least one author was listed with a German affiliation, that the study included original data and was published in an international journal with peer review. RESULTS: This review included 39 studies, which were performed based on 29 original data sets. The median proportion of women was 53.7% and the median age 45.1 years. The 1­year prevalence of hand eczema varied depending on the sample and type of data collection from 0.24% to 9.2%. The lifetime prevalence was estimated to be 2.6-16.0% and the point prevalence in dermatological practice was 6.7 %. In studies assessing the impact of hand eczema in specific occupations, women were underrepresented, large studies were carried out for metal workers but only a few small studies for nursing personnel. CONCLUSION: There is a lack of knowledge concerning the epidemiology of hand eczema in the general German population. While international studies found the first occurrence of hand eczema to be between the ages of 26 and 28 years, the mean age of patients seen in private dermatological practice in Germany was 20 years higher. These findings suggest that patients do not consult a dermatologist when hand eczema first appears, which can lead to a more severe course of the disease.

The course of chronic itch in hemodialysis patients: results of a 4-year follow-up study of GEHIS (German Epidemiological Hemodialysis Itch Study).

BACKGROUND: Chronic itch (CI) is a frequent symptom in hemodialysis (HD) patients. Previous studies demonstrated great impairments of general well-being and health-related quality of life (HRQOL) as well as a higher mortality in those suffering from CI. OBJECTIVE: The German Epidemiological Hemodialysis Itch Study (GEHIS) is a representative cohort of HD patients in Germany. All patients were followed up 4 years later. The current analyses present data on the course of CI in HD patients, its associated factors including comorbidities, laboratory values and HRQOL. METHODS: We assessed sociodemographic data, routine laboratory values, comorbidities, HRQOL (SF-12), depression and anxiety (HADS), sleep (duration and quality) and in those suffering from CI characteristics, intensity of CI and itch-related quality of life (ItchyQoL). Those with CI were offered a dermatological examination and CI was classified according to the IFSI classification. Patients were asked if they had consulted a physician about CI. RESULTS: Of the patients who had suffered from CI in 2013 (n = 234), 90.5% (212) patients could be followed up. About 36.3% (n = 85) had died, 9.8% (n = 23) had received a kidney transplant in the meantime. A total of 52 HD patients still suffered from CI, in 52 CI had stopped. Those patients still suffering from CI (n = 52) reported a higher mean itch intensity, lower ItchyQoL, higher levels of anxiety and a lower mean sleeping time in 2013. On the other hand, those who did not suffer from CI anymore showed a significant increase of HRQOL compared to 2013. There was no significant difference in dialysis characteristics and laboratory values except for albumin. Only a minority of patients in HD had consulted a dermatologist because of CI (29.9%). CONCLUSION: Our data demonstrate that CI is a persisting symptom in 50% of the HD patients and when it disappears HRQOL recovers. We confirm that CI is a disregarded symptom in HD patients.

Prevalence of skin disease in a population-based sample of adults from five European countries.

BACKGROUND: There is a lack of prevalence data on skin diseases in the general adult population; most studies have been carried out in small, national or consecutive clinical samples. OBJECTIVES: To determine the prevalence of common skin disease in the general European population and to assess differences in the characteristics of treatment between countries. METHODS: A random sample consisting of 12 377 participants aged 18-74 years was drawn from the general population of five European countries (Germany, Italy, the Netherlands, Portugal and Sweden). This was a cross-sectional study and all participants were interviewed using a standardized questionnaire that assessed the occurrence of 10 common skin diseases during lifetime, past year and past month. If a skin disease was reported, we additionally assessed who performed the diagnosis and treatment, and whether drugs had been prescribed. RESULTS: The most common skin disease was warts (41·3%), followed by acne (19·2%) and contact dermatitis (15·0%). In general, women were more often affected by skin diseases compared with men; only skin cancer had a slightly higher prevalence in men. The prevalence of skin diseases in northern countries (Germany, the Netherlands and Sweden) was generally higher than in the southern countries (Italy and Portugal). In the Netherlands the treatment of skin diseases was less often performed by a dermatologist compared with the other countries. CONCLUSIONS: The prevalence estimates reported in this study are derived from a representative sample of the general population. Data assessment was performed comprehensively across countries, thus country-specific prevalence estimates are comparable.

Patterns of chronic hand eczema: a semantic map analysis of the CARPE registry data.

BACKGROUND: Hand eczema has a high incidence and prevalence and has a negative impact on both physical and psychological well-being, with the risk of persistence as a chronic condition. Epidemiological studies on hand eczema provided mainly descriptive and risk analyses, but pattern analyses of variables associated with hand eczema, in particular chronic hand eczema, have not been explored to date. OBJECTIVES: To investigate and display the semantics of associations between variables of hand eczema obtained from the Swiss and German registries of chronic hand eczema (CARPE) to dissect patterns and novel links. METHODS: This was a cross-sectional study on selected variables from the CARPE registries. Associations between variables were analysed by means of an autoassociative system. A semantic connectivity map was generated by using a maximum spanning tree algorithm. RESULTS: Baseline datasets of 1466 patients with chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational exposure had the highest impact in the total and country cohorts. We identified two areas of exposure linked to corresponding occupations that clearly demarcated the sexes. CONCLUSIONS: This study, using semantic connectivity as a novel method of data analysis, reveals the complexity of features characterizing chronic hand eczema as well as novel association patterns that deserve further investigation.

Measurement properties of quality-of-life measurement instruments for infants, children and adolescents with eczema: a systematic review.

BACKGROUND: Quality of life (QoL) is one of the core outcome domains identified by the Harmonising Outcome Measures for Eczema (HOME) initiative to be assessed in every eczema trial. There is uncertainty about the most appropriate QoL instrument to measure this domain in infants, children and adolescents. OBJECTIVES: To systematically evaluate the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in infants, children and adolescents with eczema. METHODS: A systematic literature search in PubMed and Embase, complemented by a thorough hand search of reference lists, retrieved studies on measurement properties of eczema QoL instruments for infants, children and adolescents. For all eligible studies, we judged the adequacy of the measurement properties and the methodological study quality with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results from different studies were summarized in a best-evidence synthesis and formed the basis to assign four degrees of recommendation. RESULTS: Seventeen articles, three of which were found by hand search, were included. These 17 articles reported on 24 instruments. No instrument can be recommended for use in all eczema trials because none fulfilled all required adequacy criteria. With adequate internal consistency, reliability and hypothesis testing, the U.S. version of the Childhood Atopic Dermatitis Impact Scale (CADIS), a proxy-reported instrument, has the potential to be recommended depending on the results of further validation studies. All other instruments, including all self-reported ones, lacked significant validation data. CONCLUSIONS: Currently, no QoL instrument for infants, children and adolescents with eczema can be highly recommended. Future validation research should primarily focus on the CADIS, but also attempt to broaden the evidence base for the validity of self-reported instruments.

Prevalence of contact allergy in the general population in different European regions.

BACKGROUND: Population-based studies about contact allergy are scarce. OBJECTIVES: To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. METHODS: A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. RESULTS: In total, 27·0% [95% confidence interval (CI) 25·5-28·5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (≥ 1%) were found for nickel (14·5%, 95% CI 13·2-15·8), thiomersal (5·0%, 95% CI 4·2-5·8), cobalt (2·2%, 95% CI 1·7-2·7), FM II (1·9%, 95% CI 1·5-2·5), FM I (1·8%, 95% CI 1·4-2·3), HICC (1·4%, 95% CI 1·0-1·9), p-tert-butylphenol formaldehyde resin (1·3%, 95% CI 0·9-1·7) and para-phenylenediamine (1·0%, 95% CI 0·6-1·3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15·1%, 95% CI 13·8-16·3) had an increased risk for contact allergy (odds ratio 1·9, 95% CI 1·5-2·5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7·6%, 95% CI 6·7-8·6; odds ratio 1·0, 95% CI 0·7-1·4). CONCLUSIONS: Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced.

Measurement properties of adult quality-of-life measurement instruments for eczema: a systematic review.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has identified quality of life (QoL) as a core outcome domain to be evaluated in every eczema trial. It is unclear which of the existing QoL instruments is most appropriate for this domain. Thus, the aim of this review was to systematically assess the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in adult eczema. METHODS: We conducted a systematic literature search in PubMed and Embase identifying studies on measurement properties of adult eczema QoL instruments. For all eligible studies, we assessed the adequacy of the measurement properties and the methodological quality with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis summarizing findings from different studies was the basis to assign four degrees of recommendation (A-D). RESULTS: A total of 15 articles reporting on 17 instruments were included. No instrument fulfilled the criteria for category A. Six instruments were placed in category B, meaning that they have the potential to be recommended depending on the results of further validation studies. Three instruments had poor adequacy in at least one required adequacy criterion and were therefore put in category C. The remaining eight instruments were minimally validated and were thus placed in category D. CONCLUSIONS: Currently, no QoL instrument can be recommended for use in adult eczema. The Quality of Life Index for Atopic Dermatitis (QoLIAD) and the Dermatology Life Quality Index (DLQI) are recommended for further validation research.

Prevalence of fragrance contact allergy in the general population of five European countries: a cross-sectional study.

BACKGROUND: Contact allergy to fragrances is assessed mostly in clinical populations of patients. Studies in the general population are scarce and vary in their methodology across countries. OBJECTIVES: To determine the prevalence of fragrance contact allergy in the European general population and to assess the clinical relevance of positive patch test reactions to different fragrances. METHODS: In five European countries (Germany, Italy, the Netherlands, Portugal and Sweden) a random sample from the general population aged 18-74 years was drawn. In total, 12 377 subjects were interviewed in this cross-sectional study and a random sample (n = 3119) was patch tested using the TRUE Test and Finn Chamber techniques. Patch test procedures were harmonized by mandatory training before the study and monitoring during the study. RESULTS: The highest prevalence for contact allergy of 2·6% [95% confidence interval (CI) 2·1-3·2] was found for fragrance mix (FM) I in petrolatum, with a high content of atranol and chloratranol, followed by 1·9% (95% CI 1·5-2·4) for FM II in petrolatum. The conservatively estimated prevalence of fragrance contact allergy was 1·9% (95% CI 1·5-2·5). This is defined as the existence of a positive patch test to FM I or FM II; any of their individual materials; Myroxylon pereirae; sesquiterpene lactones or 3- and 4-hydroxyisohexyl 3-cyclohexene carboxaldehyde that show clinical relevance, defined conservatively as lifetime avoidance of scented products and an itchy skin rash lasting > 3 days in a lifetime. Using the reported lifetime prevalence of any contact dermatitis instead of the lifetime prevalence of any itchy skin rash, the prevalence is 0·8% (95% CI 0·5-1·2). The prevalence rates of contact allergy to fragrances in women are about twice those in men. CONCLUSIONS: This study helps to identify targets for prevention of fragrance allergy.

The Quality of Life in Hand Eczema Questionnaire (QOLHEQ): validation of the German version of a new disease-specific measure of quality of life for patients with hand eczema.

BACKGROUND: Health-related quality of life (HRQOL) is widely used as a patient-reported outcome to evaluate clinical trials. In routine care it can also be used to improve treatment strategies or to enhance patients' self-awareness and empowerment. Therefore a disease-specific instrument is needed that assesses in detail all the impairments caused by the disease of interest. For patients with hand eczema (HE) such an instrument was developed by an international expert group, but its measurement properties are unknown. OBJECTIVES: To validate the German version of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ), which covers the domains of (i) symptoms, (ii) emotions, (iii) functioning and (iv) treatment and prevention. METHODS: The QOLHEQ was assessed up to three times in 316 patients with HE to test reliability and sensitivity to change. To test construct validity we also assessed several reference measures. The scale structure was analysed using the Rasch model for each subscale and a structural equation model was used to test the multi domain structure of the QOLHEQ. RESULTS: After minor adaptions of the scoring structure, all four subscales of the QOLHEQ did not significantly misfit the Rasch model (α > 0·05). The fit indices of the structural equation model showed a good fit of the multi domain construct with four subscales assessing HRQOL. Nearly all a priori-defined hypotheses relating to construct validity could be confirmed. The QOLHEQ showed a sensitivity to change that was superior compared with all reference measures. CONCLUSIONS: The QOLHEQ is ready to be used in its German version as a sensitive outcome measure in clinical trials and for routine monitoring. The treatment-relevant subscales enable its use to enhance patients' self-awareness and to monitor treatment decisions.