Hand eczema:impact, treatment and outcome measures

Hand eczema is common and can have a large impact on the quality of life of those affected. In this thesis, this impact is studied. Studies into the financial cost of hand eczema are reviewed. Total yearly costs per person vary from €1311 - €9792. Presenteeism (working while having a disease) is often overlooked. It is shown that it is common in more severe hand eczema, often with an occupational cause, and frequently has intrinsic reasons. Studies into the treatment of hand eczema show that azathioprine may be considered in severe hand eczema, although it often has side effects. The novel drug dupilumab probably holds promise for the future treatment of hand eczema. Performing studies and measuring patients is not very useful if unvalidated measurement instruments are used. Therefore, the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) and the Hand Eczema Severity Index (HECSI) are extensively studied in this thesis. For the QOLHEQ national validation of the Dutch version is performed and cross-cultural validation was done for multiple language versions. For the QOLHEQ and HECSI, interpretability is studied to assign meaning to single scores and change scores. Also, it is assessed what the minimally important change is that a patient needs to obtain on these instruments to be regarded truly and importantly changed when compared with an earlier measurement

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

Presenteeism in a Dutch hand eczema population-a cross-sectional survey

Background: Presenteeism (attending work despite complaints and ill health, which should prompt rest and absence) has been overlooked in the field of hand eczema. Objectives: To examine the 1-year prevalence of presenteeism related to hand eczema in a population of hand eczema patients who visited a tertiary referral centre. Secondary objectives: to identify intrinsic/extrinsic reasons for presenteeism and to evaluate associated factors. Methods: This was a cross-sectional questionnaire study. Presenteeism was defined as "going to work despite feeling you should have taken sick leave because of hand eczema". Respondents answered questions about socio-demographic factors, clinical features, occupational characteristics, and hand eczema related to occupational exposure. Results: Forty-one per cent (141/346) of patients who had both worked and had hand eczema during the past 12 months reported presenteeism. The most often reported reasons were: "Because I do not want to give in to my impairment/weakness" (46%) and "Because I enjoy my work" (40%). Presenteeism was associated with: mean hand eczema severity; absenteeism because of hand eczema; improvement of hand eczema when away from work; and high-risk occupations. Conclusions: In this study, presenteeism was common and predominantly observed in patients with more severe hand eczema and occupational exposure. The most frequently reported reasons for presenteeism were of an intrinsic nature

Validity, reliability, responsiveness and interpretability of the Recap of atopic eczema (RECAP) questionnaire

BACKGROUND: Limited research has been conducted on the measurement properties of the Recap of atopic eczema (RECAP) questionnaire, particularly in relation to interpretability. OBJECTIVES: To investigate the validity, reliability, responsiveness and interpretability of the Dutch RECAP in adults with atopic dermatitis (AD). METHODS: We conducted a prospective study in a Dutch tertiary hospital, recruiting adults with AD between June 2021 and December 2022. Patients completed the RECAP questionnaire, reference instruments and anchor questions at the following three timepoints: baseline, after 1-3 days and after 4-12 weeks. Hypotheses testing was used to investigate single-score validity and change-score validity (responsiveness). To assess reliability, both standard error of measurement (SEMagreement) and intraclass correlation coefficient (ICCagreement) were reported. To assess the interpretability of single scores, bands for eczema control were proposed. To investigate the interpretability of change scores, both smallest detectable change (SDC) and minimally important change (MIC) scores were determined. To estimate the MIC scores, four different anchor-based methods were employed: the mean change method, 95% limit cut-off point, receiver operating characteristic curve and predictive modelling. RESULTS: In total, 200 participants were included (57.5% male sex, mean age 38.5 years). Of the a priori hypotheses, 82% (single-score validity) and 59% (responsiveness) were confirmed. Known-group analyses showed differences in the RECAP scores between patient groups based on disease severity and impairment of the quality of life. The SEMagreement was 1.17 points and the ICCagreement was 0.988. The final banding was as follows: 0-1 (completely controlled); 2-5 (mostly controlled); 6-11 (moderately controlled); 12-19 (a little controlled); 20-28 (not at all controlled). Moreover, a single cut-off point of ≥ 6 was determined to identify patients whose AD is not under control. The SDC was 3.2 points, and the MIC value from the predictive modelling was 3.9 points. Neither floor nor ceiling effects were observed. CONCLUSIONS: The RECAP has good single-score validity, moderate responsiveness and excellent reliability. This study fills a gap in the interpretability of the RECAP. Our results indicate a threshold of ≥ 6 points to identify patients whose AD is 'not under control', while an improvement of ≥ 4 points represents a clinically important change. Given its endorsement by the Harmonising Outcome Measures for Eczema initiatives, the results of this study support the integration of RECAP into both routine clinical practice and research settings.</p

Study protocol: Efficacy of oral alitretinoin versus oral cyclosporine A in patients with severe recurrent vesicular hand eczema (ALICsA)::A randomised prospective open-label trial with blinded outcome assessment

INTRODUCTION: Systemic treatment with alitretinoin is registered for all clinical types of severe chronic hand eczema. However, it is especially effective in the hyperkeratotic subtype and less effective in non-hyperkeratotic forms. Cyclosporine A (cyclosporine) is prescribed for hand eczema in daily practice as well. It has shown to be particularly effective in patients with vesicular hand eczema. The primary objective of this study is to compare efficacy of alitretinoin and cyclosporine in the treatment of severe recurrent vesicular hand eczema. METHODS AND ANALYSIS: This is an investigator-initiated randomised prospective open-label trial with blinded outcome assessment. Severity assessments and laboratory measurements will be conducted corresponding to daily practice. The study population will consist of 72 adult patients (age 18-75 years) with severe recurrent vesicular hand eczema. Patients are treated with either (group I) alitretinoin 30 mg once daily or (group II) cyclosporine with a starting dose of 5 mg/kg/day and a decrease in dosage after 8 weeks to 3-3.5 mg/kg/day. The treatment period is 24 weeks for both drugs. Primary endpoint for efficacy is response to treatment, defined as an improvement of ≥2 steps on a Physician Global Assessment, using a validated Photoguide, after 24 weeks of treatment. Secondary endpoints are improvement of Hand Eczema Severity Index, Quality of Life in Hand Eczema Questionnaire and a Patient Global Assessment. Adverse events and time to response will be registered. Furthermore, cost-utility, quality-adjusted life years and cost-effectiveness will be assessed with the EQ-5D-5L questionnaire while monitoring costs. ETHICS AND DISSEMINATION: This protocol was reviewed and approved by the Medical Ethical Review Board of the University Medical Centre Groningen (reference METc 2015/375). The study will be conducted according to the principles of the Declaration of Helsinki, in accordance with the Dutch Medical Research Involving Human Subjects Act. TRIAL REGISTRATION NUMBER: NCT03026946; Pre-results

Effect of dupilumab on hand eczema in patients with atopic dermatitis:An observational study

Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI-75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient-reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty-seven patients were included (32 males; mean age, 45 years). HECSI-75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0-164; 95% within-subject confidence interval, 46.4-52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation [SD], 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI-75 and HECSI-75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema

The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children

Background The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. Objectives To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. Methods A prospective validation study was conducted in children (aged&lt;12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0=baseline; T1=after 1–7 days; T2=after 4–8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. Results A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses. Excellent reliability was found (ICCagreement=0.94, 95% confidence interval 0.90–0.96). The SEMagreement was 1.9 points. The final banding was 0–1 (completely controlled), 2–7 (mostly controlled), 8–12 (moderately controlled), 13–18 (a little controlled) and 19–28 (not at all controlled). A cutoff point of≥8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. Conclusions The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of≥6 points can be regarded as a real and important change in children with AD.</p

The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children

Background The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. Objectives To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. Methods A prospective validation study was conducted in children (aged&lt;12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0=baseline; T1=after 1–7 days; T2=after 4–8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. Results A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses. Excellent reliability was found (ICCagreement=0.94, 95% confidence interval 0.90–0.96). The SEMagreement was 1.9 points. The final banding was 0–1 (completely controlled), 2–7 (mostly controlled), 8–12 (moderately controlled), 13–18 (a little controlled) and 19–28 (not at all controlled). A cutoff point of≥8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. Conclusions The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of≥6 points can be regarded as a real and important change in children with AD.</p

Which outcomes have been measured in hand eczema trials? A systematic review:A systematic review

The considerable heterogeneity of outcomes and measurement instruments in hand eczema trials substantially limits the evidence synthesis concerning therapeutic and preventive interventions. Therefore, the Hand Eczema Core Outcome Set (HECOS) initiative is developing a core outcome set for future trials. The first objective was to identify outcomes that were measured in previous trials, to group them in domains, and to identify their measurement instruments. We conducted a systematic review of controlled and randomized controlled hand eczema trials published since 2000. Sixty-one eligible studies were identified. Each assessed one or more of 47 outcomes in the "skin" domain. Eighteen trials (30%) additionally focused on preventive behaviour in risk occupations. Quality of life was measured in 13 studies (21%). Thirty-two distinct named instruments were applied, but 223 measurements (62%) were conducted with unnamed instruments. Only 32 studies (52%) defined a primary outcome. Twenty-nine trials (48%) provided some information on adverse events, but none gave any references concerning relevant methods. Our review confirms the need to harmonize outcome measurements in hand eczema trials. The findings form the basis for a consensus process to generate a core outcome set to improve the explanatory power and comparability of future hand eczema studies.</p