Subjective well-being in patients with pemphigus: a path analysis

Background Pemphigus is a chronic autoimmune blistering disease of the skin and mucosa severely impairing patients’ health-related quality of life (HRQoL). To date, no studies have measured subjective well-being in terms of life satisfaction in pemphigus. Our main objective was to evaluate satisfaction with life in patients with pemphigus, and to analyse its relationship with clinical severity and HRQoL. Methods A cross-sectional survey was carried out enrolling 77 patients with pemphigus. Subjective well-being was measured using the Satisfaction with Life Scale (SWLS). HRQoL was assessed by the Dermatology Life Quality Index (DLQI) and EQ-5D-5L. Disease severity was measured by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Results Mean ABSIS, DLQI, EQ-5D-5L and SWLS scores of patients were 11.7 (SD 17.3), 5.4 (6.8), 0.84 (0.22) and 4.76 (SD 1.52), respectively. The proportion of patients indicating extreme dissatisfaction, dissatisfaction, slightly below average in life satisfaction, average satisfaction, high satisfaction and very high satisfaction with life was 6 (7.8%), 5 (6.5%), 14 (18.2%), 16 (20.8%), 21 (27.3%) and 15 (19.5%), respectively. Life satisfaction was independent from age, gender, level of education and type of disease. A path analysis revealed that there was no direct relationship between ABSIS and SWLS (beta = − 0.09; p = 0.428); however, the following indirect path was confirmed: ABSIS → DLQI → EQ-5D-5L → SWLS. Conclusions Disease severity and HRQoL measures regularly used to assess patients’ health status may be complemented with a measure of subjective well-being, such as SWLS, to achieve a more holistic assessment of patients’ lives and optimise pemphigus care.


Introduction
Pemphigus is a rare, autoimmune blistering disease with two major subtypes pemphigus vulgaris and pemphigus foliaceus [1]. Pemphigus vulgaris accounts for approximately 70-90% of all cases with an annual incidence rate of 0.76-32 per million [2,3]. Mean age of onset is usually between 50 and 60 years. Pemphigus causes blisters and erosions developing on the skin or mucous membranes, such as in the mouth. Physical symptoms include itching, skin burning and pain. Pemphigus has a strong influence on patients' health-related quality of life (HRQoL), but it largely affects other aspects of patients' life, such as social activities or productivity [4][5][6]. It has been shown that pemphigus is associated with one of the largest HRQoL impairment among chronic skin diseases [4,5,[7][8][9].
Recently, subjective well-being has gained increasing attention in health policy. Subjective well-being reflects an overall evaluation of the quality of a person's life from their own perspective [10]. Evidence on subjective measures of well-being is in the focus of interest to provide a basis for reimbursement decisions about health technologies [11]. To use well-being outcomes in resource allocation decisions, the relationship between subjective well-being and the different dimensions of health, such as clinical symptoms, disease-specific and general HRQoL, needs to be explored [12]. Life satisfaction is a core indicator of people's subjective well-being. Satisfaction with life can be used as an outcome measure, as it is directly related to HRQoL. In patients suffering from chronic diseases, both physical and mental problems may have a substantial negative impact on satisfaction with life [13].
Patients' interpersonal relationships, social activities, sexual life and self-esteem are commonly adversely affected by chronic dermatological diseases [14]. In addition, patients may be dissatisfied with treatments and healthcare in general. Unemployment rate was also found higher in chronic skin diseases compared to health controls, and a proportion of patients also face a lower earning potential [15][16][17][18]. Dissatisfaction with life has been earlier reported in patients with atopic dermatitis, psoriasis, hidradenitis suppurativa, melanoma, systemic lupus erythematosus and urticaria [19][20][21][22][23][24][25]. Life satisfaction, however, has not yet been measured in pemphigus patients. Therefore, our main objective was to evaluate the satisfaction with life in patients with pemphigus and to analyse the relationship between severity of clinical symptoms, HRQoL and life satisfaction as an indicator of subjective well-being.

Study population and setting
Between December 2014 and June 2017, a cross-sectional study was conducted in four academic dermatology departments in Hungary. Consecutive patients over 18 years of age diagnosed with any form of pemphigus were enrolled after an informed consent form was read and signed. Permission for conducting the study was granted by the National Scientific and Ethical Committee (reference No. ETT-TUKEB 27416-3/2016/EKU).
First part of the survey asked patients about demographics, employment status, self-reported disease severity, utilisation of healthcare services in the past 12 months, HRQoL, and satisfaction with life. Dermatologists filled in the second part of the questionnaire. Based on medical records they provided data on clinical characteristics, medications, medical history and disease severity.

EQ-5D-5L
EQ-5D-5L is a widely used generic instrument to assess general HRQoL [26,27]. It consists of two parts: a descriptive system and a visual analogue scale (EQ VAS). The descriptive system involves the following five dimensions of general HRQoL: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension, patients may choose from five response levels (no problems = 1, slight problems = 2, moderate problems = 3, severe problems = 4 and unable to/extreme problems = 5) resulting in a total of 3125 (5 5 ) unique health states. In the absence of a national value set in Hungary, the value set for England developed by Devlin et al. was applied in this study to derive EQ-5D index scores [28]. Thus, index scores may range from -0.285 to + 1, where − 0.285 corresponds to the worst and +1 to the best possible HRQoL. The second part of the instrument, EQ VAS is a 20-cm long, vertical visual analogue scale with endpoints of '0' (the worst health you can imagine) and '100' (the best you can imagine) recording patients' self-rating of their overall health.

DLQI
Dermatology Life Quality Index (DLQI) is a skin-specific self-reported questionnaire [29,30]. It consists of ten items covering the common problems affecting HRQoL of patients with skin diseases, such as symptoms, side effects of treatment, daily activities, work or school, personal relationships, leisure activities, and feelings of embarrassment. Each item is scored on a 4-point scale: 'not at all' or 'not relevant' = 0, 'a little' = 1, 'a lot' = 2 and 'very much' = 3. DLQI total score is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0, where the higher the score, the more HRQoL is impaired.

SWLS
The Satisfaction with Life Scale (SWLS) is an extensively used questionnaire to quantify people's global judgement on their subjective well-being [31]. The Hungarian version of SWLS showed a good internal consistency reliability (Cronbach's α 0.84), convergent validity with the Rosenberg Self-esteem Scale and the Purpose in Life Test and an excellent test-retest reliability [32]. SWLS is a five-item instrument each of which is rated on a 7-point scale ranging from 'strongly disagree' to 'strongly agree'. The total score was estimated as the average of the five items resulting in a score between 1 and 7, where a higher score reflects a greater life satisfaction for the individual [31]. The following cut-off scores were used to classify patients into SWLS groups: 1-2 ('extremely dissatisfied'), 2-3 ('dissatisfied'), 3-4 ('slightly below average satisfaction'), 4-5 ('average satisfaction'), 5-6 ('satisfied') and 6-7 ('highly satisfied') [33].

Statistical analysis
First, sample and SWLS item characteristics were computed. As a preliminary analysis, Pearson's correlation coefficients were calculated to explore the relationships between the outcome measures. A correlation coefficient of 0-0.39 was defined as weak, 0.40-0.79 as moderate, and 0.80-1 as a strong correlation. The differences in SWLS scores between subgroups of patients were compared using Mann-Whitney U test.
We conducted a path analysis to test a hypothesized model predicting SWLS scores from EQ-5D-5L index, DLQI, ABSIS scores. Among the four variables the following six paths were hypothesized and tested: (1)  and (6) EQ-5D-5L → SWLS (+). To determine whether the expected model was plausible with the data, we used a Chi-square test statistic. The following goodness-of-fit indices were used based on Hu and Bentler's recommendations: comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) [38]. A CFI of > 0.95 was considered as an indicative of good fit. Acceptable threshold values of RMSEA and SRMR were ≤ 0.06 and ≤ 0.08, respectively. p values less than 0.05 were taken as statistically significant. The path analysis was conducted using AMOS 23, all other analyses were performed using SPSS 25.0 (Armonk, NY: IBM Corp.).

Results of the path analysis model
The path analysis model we evaluated is depicted in Fig. 2.

Discussion
The aim of the present study was to investigate life satisfaction as a proxy for subjective well-being and its predictors in pemphigus patients through a path analysis. The mean SWLS score was 4.76 indicating an overall average satisfaction with life. Nearly one-third (32.3%) of patients rated their satisfaction with their life to be 'below average'. Life satisfaction was independent from patients' age, gender, level of education and type of disease. A path analysis revealed the following indirect path: ABSIS → DLQI → EQ-5D-5L → SWLS. Physician's objective assessment of disease severity (ABSIS) had no direct impact on life satisfaction. This route highlights the mediating effect of the patients' perception about HRQoL on satisfaction with life.
Coping with the daily limitations caused by a chronic disease often affects patients' perception of health and satisfaction with life [39]. Previous research has shown significantly lower life satisfaction in patients with various chronic skin diseases [19][20][21][22][23][24][25]. For example, 16.6% of patients with atopic dermatitis in the US reported being at least somewhat dissatisfied with life [25]. In our study, 14.3% of patients declared to be dissatisfied or highly dissatisfied. A potential explanation for this could be that    the majority of patients were well-treated and indicated a relatively low disease severity and less deterioration in their HRQoL, which was very likely responsible for the rather positive results regarding life satisfaction. Earlier research suggests a good validity of the EQ-5D-5L in pemphigus patients [8]. Nevertheless, it may fail to capture some of the broader impact of pemphigus on HRQoL and subjective well-being [11]. For example, in a recent survey among members of the general population in the UK, respondents identified several important aspects of health that are not covered by the five dimensions of the EQ-5D, such as mental and emotional health and happiness [40]. Non-health outcomes including ability to work, financial security and social support in one's life might be important determinants of life satisfaction.
A practical implication of our study is that objective perception of the physician on disease severity only has an indirect effect on satisfaction with life. In routine practice, disease severity and HRQoL instruments regularly used to assess patients' health status may be complemented with a measure of subjective well-being, such as SWLS to achieve a more holistic assessment of patients' lives and optimise pemphigus care. This would also enable the use of subjective well-being outcomes to aid health policy decisions. This is the first study in the literature to report on life satisfaction in pemphigus patients. Furthermore, our analyses were based on a relatively large number of patients, considering the rarity of the disease. Among the study's limitations, it needs to be acknowledged that the study was conducted in university dermatology departments, and systematic selection bias due to centre effects could have been present. Thus, the results may not be representative of the entire population of patients with pemphigus. However, the study population included a large variety of pemphigus patients in terms of clinical characteristics and severity. Second, many other factors possibly influencing life satisfaction have not been measured in this survey. Further research is required to identify unexplored the drivers of subjective well-being in pemphigus patients.
In conclusion, an overall average satisfaction with life was identified in patients with pemphigus. A higher level of general HRQoL is the major determinant of life satisfaction in pemphigus patients. The path analysis identified skin-specific HRQoL and disease severity as indirect predictors of satisfaction with life. These results underscore the importance of achieving remission in benefiting the lives of patients with pemphigus.