Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe

Comparing HRQOL and economic burden across rare diseases helps to inform priority setting for healthcare resource allocation [4, 11, 15, 26]. Our study purports to be the first of its kind to provide comprehensive information on the costs of EB across several countries, and adds to the existing literature on EB cost and HRQOL impact.

The average EQ-5D index score for adult patients with EB was estimated at between 0.49 (Hungary) and 0.71 (Sweden). Patient HRQOL was not similar across the countries, but consistently lower than general population reference values.

Our results suggest that individuals living with EB have markedly lower HRQOL than the general population and, by extension, their caregivers also suffer decreased HRQOL.

This analysis highlights the importance of studying the economic consequences of EB and interpreting the results in an international context. The results of our analysis provide insights into the distribution of the costs of EB and the impact of EB on national expenditures for healthcare. We show that, in 2012, the estimated average annual cost was €17,671, €14,931, €46,116, €9809, €49,233, €43,137, €9509, and €19,758, for patients in Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the UK, respectively. The average annual cost across all countries was estimated at €31,390 per patient, with the highest proportion of costs being attributed to direct non-healthcare (74.8 % of total), followed by direct healthcare (18.0 % of total) and productivity loss (7.2 %). Patients with a lower disease severity (as categorised through their BI scores, 91–100) were associated with a lower average cost of €6961 per patient, compared to patients with a higher disease severity (BI score < 91) that were associated with a higher average cost of €48,491.

The high costs of informal care underpin the social economic burden of EB, accounting for more than half of total costs. The clear divide and hidden social costs of EB are relevant to policy-makers, especially when contemplating the impact across tiers of family income [7].

We found that EB had a consistent impact on the HRQOL of patients and their caregivers regardless of the country. In adults, direct healthcare costs, especially hospitalisations, medical visits and health material, represented the vast majority of costs, while in children, medical visits, hospitalisations and direct non-healthcare informal costs, i.e. caregivers’ dedication time, were especially predominant.

A recently published study analysing the socioeconomic impact of ten rare diseases identified no available costing studies of EB [27], apart from an old study that examined the cost-effectiveness of the “Kozak protocol” in treating nine children at a hospital in the Canadian province of Ontario; however, due to a response indicating some serious data discrepancies, these costs were not studied in depth [28, 29].

The only other quantitative study to quantify the HRQOL burden of EB in the UK used the Dermatology Life Quality Index (DLQI) in a Scottish population [5]. HRQOL loss due to EBS and DEB was observed to be similar to severe psoriasis and atopic eczema [5], where children ranked worse than adults. The DLQI was criticised for underestimating the impact of more severe types of EB by proposing questions on activities that may naturally be incompatible with their daily lives (i.e. sports, gardening, shopping) [4‐6, 11, 26]. There are other qualitative studies, however, that have investigated particular aspects of the disease, such as the HRQOL impact of living with a gastronomy tube [30, 31], living with wounds [14], dressings and bandages [32] and their associated psychosocial impact [2]. Elsewhere, worse median EQ-5D index scores were reported for children than adults, and the occurrence of problems with mobility, self-care, usual activities and pain/discomfort was more common in children, with the exception of anxiety/depression [7]. No significant differences were observed in mean VAS scores between children and adults, but the mean adult score of 62 (±23) is comparable to our adult and adolescent scores of 66.2 (±20.7) and 65.0 (±20.4). By assessing changes in usual activities, the EQ-5D questionnaire could also succumb to the same flaws as the DLQI; consequently HRQOL values presented in our study could be underestimates. More concerned with levels of dependence in performing ADLs, the Barthel index is less likely to be hindered by the aforementioned methodological issue. Fine et al. [11] surveyed ADL scores in a sample of children, albeit on a different scale than the Barthel index, and observed that most had partial dependence on a caregiver.

Administering both the SF-36 and the Skindex-29 (dermatology specific) questionnaires has been suggested as the best option to evaluate HRQOL in EB patients, striking an adequate balance between disease specificity, conceptual validity, and comparability across diseases [4, 33]. Following this practice, one study noted that women with EB had worse HRQOL compared to men [7], and a second study classified individuals with JEB, RDEB and DDEB as having some of the poorest HRQOL amongst dermatological diseases; the milder EBS ranked close to atopic dermatitis [15]. An EB specific quality of life questionnaire (EBQOL) was developed and validated across populations, although it does fail to fully quantify psychological burden [6, 15].

Qualitative studies have attempted to describe the determinants of the lower HRQOL among patients with EB and the wider social impact this disease may have on patients and families alike, including the likely co-morbidities that may emerge as a result. For children, the main impediments were itchy skin, pain, limitations to participation in childhood activities (i.e. sports, outdoor activities), and the resulting social isolation [4, 5, 12]. Parental and family support was crucial [3, 12], but caring for a child was observed to adversely affect the parents’ marriage and decrease their likelihood of having another child [34]. The burden imposed on caregivers was related to the severity of the condition [7, 34], and was affected by perceptions of the child’s pain, the stigma associated with being different, and limitations to family activities [12]. These factors are likely to have contributed to the lower HRQOL scores reported by the caregivers in our sample.

As in children, the daily limitations on adult patients due to pain and blisters were important [12], and the social impact of EB was of significant concern [13]. Patients were said to experience distress because of the life-long, hereditary nature of the disease, as well as the social isolation, discrimination and anxiety related to the visibility of EB [2, 3, 13, 15]. In a study aiming to conduct a psychosocial and psychiatric evaluation, 82 % of patients had a deteriorated quality of life using the DLQI, and 80 % of patients experienced psychiatric symptoms for which severity was not related to EB [3].

Our study is not without limitations. We did not consider EB type classification when calculating HRQOL and cost burden. As such, even though disability status does capture some of the variation in disease severity, conclusions drawn from our subgroup analysis are restricted to broad comparisons unless the Barthel index scores of EB types are known. In addition, attributing a general HRQOL detriment to EB is complex due to the heterogeneity of severity across and within categories [1, 2, 6]. The Birmingham Epidermolysis Bullosa Severity (BEBS) score could have allowed for stratification of patients based on disease severity to provide more detailed cost estimates [10]. Though there are EB (EBQoL) and dermatology-specific (Skindex-29) HRQOL questionnaires, we used the EQ-5D as it has been deemed a valid cross-sectional, generic measure of health outcomes in rare diseases and is commonly used as the basis for economic evaluations [7, 35]. However, it does appear pertinent to argue for more accurate disease-specific tools and their wider use in the future in terms of capturing some of the salient features of individual diseases and the impact they may exert on patients, which standard tools, such as the EQ-5D, may not be able to capture [36]. A small sample size and recruitment of solely patient volunteers could have introduced a selection bias to the study, causing a preference for patients with less severe illness, as they were more likely not to be hospitalised and to be in contact with the association. If this were true, we would have underestimated the economic burden, as the high treatment costs related to hospitalisation and long-term care could not have been considered. Furthermore, recall biases are non-negligible when conducting questionnaire-based studies and, like other HRQOL studies on EB, cross-sectional data was used; restrictions as to the scope and means of our study made the collection of longitudinal data prohibitive, although this could have captured patient adaptation to their diseased state [4].

The limitations of cost-of-illness studies outlined above are generally trumped by their utility alongside population-level data in helping to formulate health policies. By adopting a bottom-up and annual approach for this study, these first estimates of the costs of EB across eight EU member states are likely to be complete and realistic.