The puzzling effect of disease severity on quality of life in epidermolysis bullosa

Epidermolysis bullosa (EB) is a rare inherited skin disorder, characterized by skin fragility.1 The condition's impact on quality of life (QoL) has been confirmed repeatedly.2-6 However, studies addressing the QoL of EB patients keep reporting a puzzling result: Even though the impact on overall QoL and functioning is higher in severely affected patients, the emotional impact is not.2, 3, 5, 6 Adaptation to chronic (skin) disease is shaped by more than clinical severity and includes psychological and behavioural processes.7 In visible skin conditions specifically, such as psoriasis, emotional reactivity and regulation have been shown to influence psychological and QoL outcomes.8 This finding was further examined using the German and Austrian subsample (n = 75) of the ‘Changes in the Socioeconomic Burden of EB in Europe’ (BUR-EB) project. We specifically investigated how the emotions and functioning-related components of QoL differ between levels of disease severity using the QoLEB questionnaire.3 The QoLEB measures functioning and emotions on a 0–3 scale. Relative mean scores Dimension sum score number of items in dimension $$ \left(\frac{\mathrm{Dimension}\ \mathrm{sum}\ \mathrm{score}}{\mathrm{number}\ \mathrm{of}\ \mathrm{items}\ \mathrm{in}\ \mathrm{dimension}}\right) $$ enabled comparisons between dimensions. Disease severity was assessed based on the presence of 14 typical EB manifestations (self-reported), selected and reviewed by the BUR-EB consortium, comprising clinicians, social scientists and representatives of patient organizations. Each manifestation was weighted by five EB-specialized clinicians according to its perceived contribution to disease severity. A median split of the weighted severity score categorized participants into a less severe (n = 38) and more severe EB (n = 37) group. To examine the interaction between QoLEB dimension and disease severity, a mixed ANOVA was performed. Dimension scores were log-transformed (log10(x + 1)) to meet assumptions of normality, which was confirmed by Shapiro–Wilk tests (p > 0.061). Box's M test showed no substantial violation of covariance homogeneity (p = 0.015) but Levene's test revealed unequal variances in the emotions dimension (p = 0.005). Given the equal group sizes and a variance ratio of 1.98, the mixed ANOVA was considered sufficiently robust but findings should be interpreted with caution.9 Transformed domain scores were also used in (Welch's) t-tests. Participants' sociodemographic and clinical characteristics, along with the QoLEB scores, are included in Table 1. In the more severe EB group, significantly lower overall QoL scores (t(73) = −3.34, p = 0.001) and functioning scores (t(73) = −3.98, p < 0.001) were observed, whereas emotion scores did not differ significantly (t(66.86) = −1.35, p = 0.182), confirming the previously reported pattern.2, 3, 5, 6 A significant interaction between dimensions and severity (F(1, 73) = 5.89, p = 0.018, η2p = 0.075) indicated that the relative contributions of emotional and functional impact to overall QoL vary by severity (Figure 1). A significant difference was found between dimensions in the less severe (t(37) = 3.16, p = 0.003) but not in the more severe EB group (t(36) = −0.27, p = 0.786). These findings suggest that the lower QoL among severely affected individuals is driven by the impact on functioning. With the functional impact as reference, the similar emotional scores across severity groups should not be interpreted as a low emotional burden in the severe EB group, but rather as a similarly substantial burden in less severely affected patients. However, even though the emotional impact appears numerically similar, it also seems to be qualitatively different, as reported by interview studies.4 A further mechanism that could underlie the similarity in emotional burden between severity groups is alexithymia, which has been associated with both the presence and severity of chronic pain,10 possibly masking the extent of emotional distress in patients with higher EB severity in the self-assessment. Additional research is warranted to confirm these findings and clarify underlying mechanisms, particularly given that multiple potential confounding factors (e.g. coping mechanisms) were not assessed. These results also have practical implications. Given the smaller number of items in the emotions dimension and the use of absolute values in the QoLEB,3 there is a risk that the overall QoL score hides a potentially substantial emotional impact. Accordingly, dimension scores should be reported and the use of relative scores can facilitate the interpretation, valuing the impact on functioning and emotions equally. The authors thank DEBRA Austria and the Interessensgemeinschaft Epidermolysis Bullosa e.V. (DEBRA Germany) for their support in facilitating data collection, as well as the patients who shared their time and experiences. The authors also gratefully acknowledge the collaboration of the BUR-EB Consortium and the physicians of the EB Centre Freiburg. This research was supported by the European Union's Horizon 2020 research and innovation programme EJP RD COFUND-EJP (825575), the Federal Ministry of Education and Research Germany (01GM2103) and DEBRA Austria. None to declare. Ethics approval was granted by the Ethics Committee of Albert-Ludwigs-University Freiburg, Germany (22-1519-S2) and by the Ethics Committee of Sigmund Freud University Vienna, Austria (VCUWJTFUBTVISE90458). All participants aged 12 years and older provided written informed consent. For participants between 12 and 17 years of age, a simplified consent form was used. For minors (<18 years of age), a parent or legal guardian also provided written informed consent and for participants aged 11 years, consent was obtained solely from a parent or legal guardian. The data that support the findings of this study are available from the corresponding author upon reasonable request.