Allergic reactivity for different dilutions of eugenol in repeated open application test and patch testing.

BACKGROUND: Eugenol is a known contact sensitiser included in fragrance mix I. OBJECTIVE: To assess the allergic reactivity to eugenol in different concentrations using patch test as well as repeated open application test (ROAT). METHODS: Overall 67 subjects from 6 European dermatology clinics participated in the study. The ROAT was performed for 21 days twice a day, applying 3 dilutions of eugenol (2.7%-0.5%) and a control. Before and after the ROAT, patch testing with 17 dilutions of eugenol (2.0%-0.00006%) and controls was performed. RESULTS: Out of the 34 subjects with contact allergy to eugenol, 21 (61.8%) showed a positive patch test before ROAT was performed, the lowest positive concentration was 0.031%. The ROAT was positive in 19 (55.9%) of the 34 subjects, the time until a positive reaction occurred was negatively associated with the concentration of the ROAT solution, as well as with the allergic reactivity of the subjects as defined by patch testing. In the patch test after ROAT, 20 of the 34 test subjects (58.8%) showed a positive reaction. In 13 (38.2%) of the 34 test subjects, the patch test result was not reproduceable, still 4 (31.0%) of these 13 subjects developed a positive ROAT. CONCLUSION: Eugenol can provoke a positive patch test reaction in a very low dose; besides, this hypersensitivity may persist even if a former positive patch test is not reproduceable.

Skin exposure to scented products used in daily life and fragrance contact allergy in the European general population - The EDEN Fragrance Study.

BACKGROUND: Fragrances are widely used in scented products used in daily life with the potential to induce skin sensitization. OBJECTIVE: To evaluate exposure to scented products and to explore associations between exposure and fragrance contact allergy. METHODS: A cross-sectional study on individuals from 18 to 74 years of age, who were randomly selected from the general population in five European countries. A random sample (N = 3119) was patch tested and interviewed on exposure to scented products. RESULTS: Female participants were strongly associated with exposure to scented products relative to male participants. Participants age 40 years and older showed an inverse association with exposure to scented products. Compared to Sweden, The Netherlands followed by Germany showed the highest overall exposure to scented products. Sensitive skin was associated with exposure to scented products and with fragrance allergy. In univariable regression analysis, exposure to leave-on products and to specific scented product subgroups was significantly associated with fragrance allergy. CONCLUSION: Exposure to scented products depends primarily on sex and age. Female sex and sensitive skin are relevant indicators for developing fragrance allergy. Because aggregate exposure, especially to scented leave-on products, may enhance the prevalence of contact allergy to fragrances, further investigations into exposure amounts and frequencies is warranted.

New evidence for construct validity and interpretability of the German Quality of Life in Hand Eczema Questionnaire (QOLHEQ).

BACKGROUND: The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is a disease-specific instrument used to assess health-related quality of life (HRQoL) in patients with hand eczema according to the domains of (a) symptoms, (b) emotions, (c) functioning, and (d) treatment/prevention. Today it is not clear what a single score of the QOLHEQ in its German-language version means to a patient. OBJECTIVES: It was the aim of this study to band the QOLHEQ score to an anchor question (AQ) in order to obtain meaningful categories of the QOLHEQ to aid its interpretation. In addition, we assessed the minimal important change (MIC) by using anchor- and distribution-based methods. METHODS: Overall n = 440 hand eczema patients were included in the study. Mean age was 47.5 years (SD 11.9); 38.4% of the sample were female. RESULTS: With a weighted kappa of 0.62, the total QOLHEQ score showed the best agreement for the following band: QOLHEQ of <17 = no impairment; QOLHEQ of 18-28 = slight impairment; QOLHEQ of 29-41 = moderate impairment; QOLHEQ of 42-79 = severe impairment; and QOLHEQ of >79 = very severe impairment. The MIC for the total score was found to be 16.5 points. CONCLUSION: This banding represents a standardized means of interpreting the QOLHEQ total score. Our results indicate that a banding study should be performed for each language version of the QOLHEQ.

Quality of life, treatment satisfaction, and adherence to treatment in patients with vesicular hand eczema: A cross-sectional study.

BACKGROUND: Recurrent vesicular hand eczema frequently has a chronic course and needs long-term treatment. OBJECTIVES: To evaluate health-related quality of life (HRQoL), treatment satisfaction, and adherence in patients with vesicular hand eczema. METHODS: Patients using one main treatment for at least three months were included. Data on HRQoL (Quality of Life in Hand Eczema Questionnaire [QOLHEQ]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication, version II), and treatment adherence (4-item Morisky Medication Adherence Scale) were collected. Univariate and multivariate regression analysis were used to predict variables associated with HRQoL. RESULTS: HRQoL was moderately impaired, with the highest impact in the QOLHEQ subdomain symptoms. Female sex, more severe hand eczema, and lower treatment satisfaction were associated with more impairment in HRQoL. Patients with severe/very severe hand eczema had significant lower "global satisfaction" scores compared with the other severity groups. The "global satisfaction" and treatment adherence in patients using systemic treatment were significantly higher compared with those with only topical treatment. CONCLUSIONS: In patients with vesicular hand eczema disease severity affects both HRQoL and treatment satisfaction. Systemic treatment of severe hand eczema could improve the severity and as a result also HRQoL, treatment satisfaction, and medication adherence.

Interpretability of the Quality Of Life in Hand Eczema Questionnaire.

The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is used to measure impairment of health-related quality of life in hand eczema. Here, we prospectively studied the interpretability of international QOLHEQ scores at three time points: baseline, after 1-3 days (T1), and after 4-12 weeks (T2). Adult patients with hand eczema completed the QOLHEQ and anchor questions for overall assessment of health-related quality of life impairment. Interpretability of single scores was assessed at baseline by defining severity bands based on agreement with the anchor questions. Smallest detectable change was calculated at T1. Minimally important change of improvement was calculated at T2 using three methods: mean cut-off, receiver operating characteristic, and 95% limit. A total of 294 adult patients were included (160 males, mean age 44.9 years). The final proposed severity band of overall QOLHEQ single scores (κ-coefficient of agreement, 0.431) was not at all, 0-10; slightly, 11-39; moderately, 40-61; strongly, 62-86; and very strongly, ≥87. Separate overall severity bands were proposed for males and females and the four subscales of the QOLHEQ. The smallest detectable change in 166 unchanged patients was 18.6 points. The preferred minimally important change, obtained with the receiver operating characteristic method, was 21.5 points. An overall QOLHEQ score of ≥22 is recommended as cut-off for a minimally important, real change.

Mortality of Haemodialysis Patients With and Without Chronic Itch: A Follow-up Study of the German Epidemiological Hemodialysis Itch Study (GEHIS).

The GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cohort study started in 2013 with 860 haemodialysis (HD) patients in 25 German dialysis units. Chronic itch (CI) has been reported to be a poor prognostic marker for patients on HD; however, this has not been investigated in a representative patient cohort. In 2017, all HD patients were contacted again to investigate mortality in those with and without CI and to identify its determinants. Patients' characteristics, study instruments and CI were assessed, as in 2013. The response rate was 84.2% (n = 724). One-year mortality was 15.3%. Mortality was significantly higher in those with secondary scratch lesions compared with those with non-affected skin. This was also true after controlling for age and sex in a multivariate model. This study demonstrates a high mortality in HD patients; however, mortality depends on itch intensity, not on the occurrence of CI itself.

Chronic hand eczema in Germany: 5-year follow-up data from the CARPE registry.

BACKGROUND: The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE). OBJECTIVES: To report comprehensive follow-up data from the CARPE registry. PATIENTS AND METHODS: We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively. RESULTS: Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased. CONCLUSIONS: Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.

Socioeconomic Status and the Prevalence of Skin and Atopic Diseases in Five European Countries.

The aim of this study was to investigate the association between socioeconomic status and the prevalence of self-reported skin and atopic diseases in the general population of 5 European countries. A random sample was drawn from the general population aged 18-74 years, based on electoral precincts. Socioeconomic status was estimated by combining net household income with the highest education of respondents. A total of 7,904 subjects were included in this analysis. The lifetime prevalence of "contact dermatitis" ranged from 13.1% (95% confidence interval (95% CI 11.8-14.4%) in subjects with low socioeconomic status, to 19.1% (95% CI 17.5-20.8%) in those with high socio-economic status. In younger subjects skin cancer was more prevalent in the middle or high socioeconomic status groups compared with the low socioeconomic status group (odds ratio 2.4; 95% CI 1.4-4.3); however, this effect was not found in elderly subjects. The lifetime prevalence for at least one atopic disease was 61.2% (95% CI 59.4-63.0%) in the low and 82.8% (95% CI 81.1-84.3%) in the high socioeconomic status group. Individuals with middle or high socioeconomic status reported an overall higher prevalence of skin and atopic diseases compared with those with low socioeconomic status. These findings may reflect differences in reporting, which are likely to result in an underdiagnoses, especially for skin cancer in the younger age groups with low socioeconomic status.

Quality of Life in Hand Eczema Questionnaire: Validation of the Japanese version of a disease-specific measure of quality of life for hand eczema patients.

Hand eczema (HE) is a common skin disease that impairs health-related quality of life (HRQOL). Impairments in HRQOL have already been reported in Japanese HE patients using the Skindex-16. Recently, an instrument to measure disease-specific HRQOL in HE patients was developed by an international expert group, consisting of domains for: (i) symptoms; (ii) emotions; (iii) functioning; and (iv) treatment and prevention. The objective of this study is to translate the English-language version of the Quality of Life Hand Eczema Questionnaire (QOLHEQ) to Japanese and then to validate the Japanese version. The Japanese version of the QOLHEQ, the Dermatological Life Quality Index (DLQI) and a questionnaire regarding basic demographic information, including patient ratings of HE severity, were distributed to Japanese HE patients. Additionally, a dermatologist evaluated patients' HE severity using the Physician Global Assessment. A total of 124 patients with a mean age of 43.7 years were included in the analysis, and 78% of the sample was female. Cronbach's alphas for the domains symptoms, emotions, functioning, and treatment and prevention were 0.76, 0.89, 0.88 and 0.81, respectively. The total QOLHEQ score showed a strong correlation with the DLQI, a moderate correlation with patient-rated severity and weak correlations with dermatologist-rated severity and the number of consultations. The Japanese version of the QOLHEQ showed excellent reliability and high validity. The Japanese version of the QOLHEQ is ready for use in epidemiological studies to evaluate HRQOL impairments in HE patients.

Prevalence of contact allergy to metals in the European general population with a focus on nickel and piercings: The EDEN Fragrance Study.

BACKGROUND: Studies on sensitization to metals in the general population are scarce. OBJECTIVES: To determine the prevalence of sensitization to metals in the general population, and factors associated with nickel sensitization. METHODS: In 5 European countries (The Netherlands, Germany, Italy, Portugal and Sweden), a random sample (N = 3119) from the general population (aged 18-74 years) was patch tested and interviewed by use of a questionnaire on exposure to metals, piercing, and jewellery. RESULTS: Overall, the age-standardized prevalences of sensitization to nickel, cobalt and chromium were, respectively, 14.5%, 2.1%, and 0.8%. The highest prevalence of nickel sensitization was seen in Portugal (18.5%) and the lowest (8.3%) in Sweden. The prevalence of cobalt sensitization varied between 3.8% (The Netherlands) and 0.9% (Italy), and the prevalence of chromium sensitization varied between 1.3% (Portugal) and 0.2% (Sweden). Significant associations were observed between nickel allergy and female sex (odds ratio [OR] 5.19; 95% confidence interval [95%CI]: 3.99-6.74), past piercing use (OR 3.86; 95%CI: 2.85-5.24), and currently having ≥3 piercings (OR 5.58; 95%CI: 4.02-7.76). CONCLUSIONS: The prevalence of sensitization to metals in the European general population was high, mostly because of nickel. The lowest prevalence of contact allergy to nickel and chromium observed in Sweden supports the effectiveness of long-standing regulation.

Persistence of contact allergy: a retrospective analysis.

BACKGROUND: Studies have shown that not all positive patch test reactions are reproducible upon retesting, that is, persistent. Non-persistent reactions might represent initial false-positive reactions, meaning that patients might unnecessarily avoid allergens. OBJECTIVES: To investigate the occurrence of both persistent and non-persistent patch test reactions, to explore possible explanations, and to investigate whether allergen-specific differences exist. METHODS: A retrospective analysis was performed on patients who were patch tested at least twice between 1 January 1995 and 31 October 2016, with at least one positive patch test reaction to an allergen that had been retested. Both univariable and multivariable analyses were performed to investigate the influence of several factors on persistence. RESULTS: Of 274 retested positive reactions in 119 patients, 183 (66.8%) reactions remained positive. The strongest predictor for non-persistence in both univariable and multivariable analyses was strength of the first patch test, with weak positive reactions being significantly less persistent. Regarding allergen groups, metals and fragrances were less persistent than other allergens. CONCLUSION: Weak positive reactions have a low persistence rate, and the dermatologist should be conservative in advising the patient on avoidance of these allergens, especially if clinical relevance is uncertain.

Guideline for translation and national validation of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ).

There is a need for well-developed and validated questionnaires to measure patient reported outcomes. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is such a validated instrument measuring disease-specific health-related quality of life in hand eczema patients. A re-validation of measurement properties is required before an instrument is used in a new population. With the objective of arriving at a guideline for translation and national validation of the QOLHEQ, we have developed the design of a reference study on how to adequately assess measurement properties of the QOLHEQ based on interdisciplinary discussions and current standards. We present a step-by-step guideline to assess translation (including cross-cultural adaptation), scale structure, validity, reproducibility, responsiveness, and interpretability. We describe which outcomes should be reported for each measurement property, and give advice on how to calculate these. It is also specified which sample size is needed, how to deal with missing data, and which cutoff values should be applied for the measurement properties assessed during the validation process. In conclusion, this guideline, presenting a reference validation study for the QOLHEQ, creates the possibility to harmonize the national validation of the various language versions of the QOLHEQ.

Cross-Cultural Validation of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ).

The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is the only instrument assessing disease-specific health-related quality of life in patients with hand eczema. It is available in eight language versions. In this study we assessed if the items of different language versions of the QOLHEQ yield comparable values across countries. An international multicenter study was conducted with participating centers in Finland, Germany, Japan, The Netherlands, Sweden, and Turkey. Methods of item response theory were applied to each subscale to assess differential item functioning for items among countries. Overall, 662 hand eczema patients were recruited into the study. Single items were removed or split according to the item response theory model by country to resolve differential item functioning. After this adjustment, none of the four subscales of the QOLHEQ showed significant misfit to the item response theory model (P < 0.01), and a Person Separation Index of greater than 0.7 showed good internal consistency for each subscale. By adapting the scoring of the QOLHEQ using the methods of item response theory, it was possible to obtain QOLHEQ values that are comparable across countries. Cross-cultural variations in the interpretation of single items were resolved. The QOLHEQ is now ready to be used in international studies assessing the health-related quality of life impact of hand eczema.

Severity and functional disability of patients with occupational contact dermatitis: validation of the German version of the Occupational Contact Dermatitis Disease Severity Index.

BACKGROUND: The Occupational Contact Dermatitis Disease Severity Index (ODDI) was designed in Australia to measure severity and functional disability in patients with occupational contact dermatitis (OCD) of the hands. The ODDI was translated into the German language with a linguistic validation process. The psychometric properties of the German version of the ODDI are still unclear. OBJECTIVES: To report the linguistic validation procedure and to perform a psychometric validation by investigating the validity and reliability of the German ODDI version in a sample of patients with OCD. METHODS: Data were drawn from the baseline assessment (T0) and first follow-up (T1) of the German chronic hand eczema (CHE) registry (CARPE). Spearman correlations of the ODDI with reference measures were computed to assess validity. Cronbach's alpha was calculated as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess retest reliability. The smallest real difference (SRD) and minimal clinically important difference (MCID) were calculated to assess sensitivity to change. Physician Global Assessment (PGA) was used as an anchor for the MCID. RESULTS: Four hundred and twenty-two patients (54.5% female, mean age 45.1 years) were included for analysis. Cronbach's alpha was found to be 0.73. The ICC was 0.79. Correlations between the ODDI total and the Dermatology Life Quality Index (rho = 0.36), and between PGA (rho = 0.48) and patient-assessed disease severity (rho = 0.40), were of moderate strength. The MCID (1.29) was found to be smaller than the SRD (1.87). CONCLUSIONS: The German ODDI version is reliable and valid for the measurement of functional impairment and disease severity in patients suffering from OCD.

Assessing health-related quality of life in hand eczema patients: how to overcome psychometric faults when using the dermatology life quality index.

Health-related quality of life (HRQOL) has become an important patient reported outcome in health service research. The dermatology life quality index (DLQI) is the most commonly used instrument in dermatology. In recent years, the psychometric properties of the DLQI have been a subject of debate as requirements of modern test theory seem not to be fulfilled. The aim of this study was to test whether those violations also occur in patients with hand eczema. We collected data of 602 hand eczema patients who participated in an inpatient dermatology rehabilitation program in Germany. In order to report meaningful scores of the DLQI, data were analysed according to the principles of modern test theory. We calibrated the DLQI using the Rasch model, resulting in a 6 item version with a range between 0-15 points. This version showed no significant misfit to the Rasch model (p>0.14). By using a Rasch analysis the results were evaluated in a second sample of hand eczema patients (n=511). Even if all demographic characteristic of this sample were different, we were able to replicate the results found in this study (p>0.21). In conclusion, we recommend to use an alternative scoring procedure as presented in this article if the DLQI is used in hand eczema patients.