Phenotype, disease severity and pain are major determinants of quality of life in Fabry disease: results from a large multicenter cohort study.

Quality of life (QoL) is decreased in patients with Fabry disease (FD). To improve QoL, it is important to understand the influence of FD related characteristics, symptoms, and complications. In this retrospective cohort study we explored the effect of pain (measured by the Brief Pain Inventory), phenotype, treatment, and FD-related complications on QoL. QoL data of Fabry patients as assessed by the EuroQol five dimension questionnaire (EQ-5D) from two international centers of excellence were collected. The aim of this study was to evaluate the effect of sex, phenotype, age, different states of disease severity, pain, and ERT on EQ-5D utilities. For 286 adult FD patients (mean age 42.5 years, 40% men, 60% classical phenotype) 2240 EQ-5Ds were available. QoL is decreased in men as well as women with FD, especially in older men with a classical phenotype. At age 50, utility was lower in men with classical FD compared to those with non-classical disease (β = -0.12, 95% CI: -0.23 - 0.01, p = 0.037) with further difference in the years thereafter. Cardiovascular complications, stroke or transient ischemic attacks, multiple FD-related complications and pain were also associated with decreased utilities. Overall, no change in utility was seen in patients on ERT over a mean follow-up of 6.1 years. FD leads to a decreased QoL compared to the general population. Disease complications and pain both negatively influence QoL. Adequate assessment and treatment of pain as well as improved strategies to prevent disease complications are needed to improve QoL in the FD population

Fabry and the brain: Incorporating patients’ illness perceptions into the physicians’ practice

Cerebral involvement is common in Fabry disease (FD). This thesis aimed to incorporate patients’ illness perception (e.g. depressive symptoms, quality of life) into the physicians’ practice (follow-up schedules and treatment). We aimed to improve prognostication, prevent cerebral involvement and stimulate appropriate use of enzyme replacement therapy (ERT). In the Dutch FD cohort, cognitive impairment, subjective cognitive complaints and depressive symptoms were all found, with a high prevalence of the latter two. Assessment of depressive symptoms using a questionnaire should be included in routine follow-up of FD patients. Progression of white matter lesions (WMLs) and infarctions was related to the patients’ age, sex and phenotype. Unexpectedly, we found no association between progression of WMLs or infarctions and ERT or cerebrovascular risk factors. This provided a sobering view of the manageability of WMLs and infarctions in FD. Patients should be informed that WMLs will increase with age, despite treatment with ERT. FD patients with a history of stroke experienced a decreased quality of life and had a higher risk of cognitive impairment, emphasizing the importance of preventing stroke. WMLs were not related to cognitive functioning or depressive symptoms, showing there is a need for clinically relevant and validated cerebral biomarkers. In conclusion, we believe that this thesis may improve communication between doctors and patient, guides the appropriate use of ERT and gives clear directions for future research. We also make a plea for longitudinal studies for FD, with smart designs and robust methodology to improve comparability and interpretability of results