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

Recurrent vesicular hand eczema frequently has a chronic course and needs long‐term treatment.


| INTRODUCTION
Hand eczema can be classified into different clinical subtypes.
Recurrent vesicular hand eczema is a typical clinical subtype that is characterized by development of small (1-2 mm) vesicles most often interdigitally or on the palms. The patient experiences episodes of vesicles mostly at unpredictable intervals, which can result in a chronic course of recurrent vesicular hand eczema. In addition to a clinical diagnosis, it is important to classify hand eczema etiologically. The cause of hand eczema is often multifactorial. It can be classified into one or more of the following etiological diagnoses: allergic contact dermatitis, irritant contact dermatitis (ICD), protein contact dermatitis, and atopic hand eczema. 1 The treatment of chronic hand eczema is often challenging and at times insufficient and unsatisfactory. 2,3 Studies on treatment effectiveness are mainly based on physician-reported outcomes. Fewer studies have actually evaluated treatment benefit in terms of patientreported outcomes. 4,5 However, chronic hand eczema can have a remarkable impact on quality of life. 2,6 To evaluate the impact of disease and treatment on physical, psychological, and social functioning, the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) was recently developed. It measures overall health-related quality of life (HRQoL) impairment in four domains: "symptoms," "emotions," "functioning," and "treatment and prevention." 7,8 Other patient-reported outcomes are treatment satisfaction and treatment adherence. 9,10 Previous studies in several therapeutic areas demonstrated a positive association between treatment satisfaction and adherence to therapy. 11 In this study we aimed to examine HRQoL, treatment satisfaction, and treatment adherence in patients with recurrent vesicular hand eczema.  For a complete overview of all variables, see the questionnaire in Data S1.
To evaluate treatment adherence four dichotomous questions (yes [1]/no [0]), the 4-item Morisky Medication Adherence Scale was used, range 0-4. A sum score of 0 represents a high patient adherence, a score of 1 or 2 represents a medium adherence, and a score of 3 or 4 represents a low adherence. 10

| Statistical analyses
Data analyses were performed using IBM SPSS Statistics version 23.0 for Windows (SPSS/IBM, New York, New York). Descriptive statistics were presented as mean together with median and range for intervalscaled variables, and as relative frequency together with absolute numbers for categorical variables. The four QOLHEQ and TSQM subdomains were analyzed separately for the group of patients with nonsystemic therapy and for the group with systemic therapy. After controlling for normal distribution, the independent sample t test was used to analyze the differences in treatment satisfaction and HRQoL between both treatment groups. Fisher's exact test was used to test difference in nominal variables between the nonsystemic and systemic groups. Univariate regression analysis included as independent variables age, gender, level of education (high vs middle/low), duration of hand eczema (years), the current treatment (nonsystemic vs systemic treatment), hand eczema severity, treatment adherence, and "global satisfaction," which were suitable for inclusion (P < .2) into the multivariate regression model. Afterwards, multivariate linear regression was used including clinical characteristics associated with treatment satisfaction. P-values less than .05 were considered statistically significant in all analyses. Standardized β-coefficients were presented, with strong correlation defined as β > 0.7, moderate correlation as 0.7 > β > 0.4, and weak correlation as 0.4 > β > 0.2. 17 The interpretability of the Dutch and International QOLHEQ (subdomain and overall) scores was published by Oosterhaven et al. 8,16 See Data S3 for the Dutch (Table S3.3) and International (Table S3.4) single score bands.
In this publication Dutch scores were presented; the International scores can be found in Data S3.

| RESULTS
In total, 168 (56.0% female) participants were included in this study.
Sociodemographic and clinical characteristics are outlined in Table 1   Nine patients were not patch tested, necessary for allergic contact dermatitis classification. n Five patients were not patch tested, necessary for allergic contact dermatitis classification. o 12 patients were not patch tested, necessary for allergic contact dermatitis classification. p Two patients were not patch tested, necessary for allergic contact dermatitis classification. q Three patients were not patch tested, necessary for allergic contact dermatitis classification.

| Treatment satisfaction
TSQM subdomain scores are presented in Table 3. Patients were most satisfied about the TSQM subdomain "side effects" and least satisfied about "effectiveness." Patients receiving systemic treatment had significantly higher TSQM treatment satisfaction scores for "effectiveness" and "global satisfaction" compared with patients receiving T A B L E 2 Health-related quality of life impairment assessed with the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) in patients with vesicular hand eczema: interpretation of the overall QOLHEQ score and the QOLHEQ subdomain scores

| Adherence
About 50% of the patients had a medium treatment adherence. In the group of patients with high treatment adherence there were significantly more females than males and significantly more patients using systemic therapy compared with nonsystemic therapy ( Table 3). The QOLHEQ and TSQM subdomains scores for different adherence groups are presented in Table 4. A high adherence was significantly associated with a lower QOLHEQ overall score and the QOLHEQ subdomain "emotions." Moreover, high adherence was associated with higher TSQM "global satisfaction" scores and a higher satisfaction about "effectiveness."

| Regression analysis
In the univariate analysis (see Data S4), taking the QOLHEQ domain score as the dependent variable, age, duration of hand eczema, education, and adherence were not associated with HRQoL. The multivariate regression model (Table 5) showed that female sex, more severe hand eczema, and lower treatment satisfaction were associated with more impairment of HRQoL (overall QOLHEQ score). This model explained 37% of the variance of the total HRQoL score (R 2 ). Severity was strongly associated with the  or had similar impairment with less severe hand eczema. 2,6,7 In the current study "functioning" was particularly affected in females.
Female patients probably had more distress related to limitations in work, leisure time, or domestic activities. Previous studies showed a considerable psychosocial burden of hand eczema and underline that anxiety and depression are more common in female patients. 2,19 In this study we did not find an association between female sex and impairment of HRQoL in the QOLHEQ subdomain "emotions." The regression analyses showed that lower "global satisfaction" was associated with more impairment of HRQoL; the standardized beta was −0.44, which indicates a moderate correlation. In previous studies in patients with gout and hypertension a correlation was also found between these outcomes. 20,21 For the total group we have shown that patients were least satisfied with "effectiveness" of treatment. In patients with severe and very severe hand eczema significantly lower satisfaction scores were found for the TSQM subdomains "effectiveness" and "global satisfaction" compared with the other severity groups. Satisfaction about "side effects" and "convenience" were similar in the different severity groups. This implies that effectiveness of treatment is the major factor affecting "global satisfaction," which is supported by previous studies on, for example, patients with psoriasis and lichen sclerosis. These studies found that patients reported treatment effectiveness as the most important factor for overall treatment satisfaction. 2 (Table 4). However, a longitudinal study is needed to verify if less emotional impairment leads to higher adherence or if adherence leads to less emotional problems. A higher medication adherence was also significantly associated with a higher "global satisfaction," while this effect was not seen in the TSQM subdomains "side effects" and "effectiveness." Some clinical and etiological characteristics need to be highlighted. Of note, half of the patients had ICD during treatment phase (>3 months) and even in the group treated with systemic therapy 40% had an ICD. In our department trained nurse practitioners provide one-to-one patient education for every patient with hand eczema. These are offered personalized glove advice to protect hands from irritant and allergic factors and improve topical treatment compliance. From the high proportion of ICD it can be deduced that despite all efforts it seems impossible for a large proportion of patients to avoid exposure to irritants.
Moreover, we found a high proportion of patients with allergic contact dermatitis (40%), compared with other studies. 32,33 A possible explanation is the fact that our center is a tertiary reference center for hand eczema. Finally, atopic dermatitis is a well-known risk factor for more severe and chronic hand eczema. 34 The number of patients with atopic hand eczema in this study was in line with previous studies (21.5%-57.5%). 32,33 A limitation of our study is the monocentric design in a tertiary was previously demonstrated to be less successful in vesicular hand eczema. 35 If alitretinoin is effective, patients will continue treatment after 3 months.
In conclusion, our results indicate that disease severity affects both HRQoL and treatment satisfaction in patients with vesicular hand eczema. Patients only using topical treatment are less satisfied with their treatment and their treatment adherence is lower. Systemic treatment of severe hand eczema could improve the severity and as a result also HRQoL, treatment satisfaction, and medication adherence.