Epidemiology of inherited epidermolysis bullosa in Germany.

BACKGROUND: Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. OBJECTIVE: Epidemiological data from different countries have been published, but none are available from Germany. METHODS: In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. RESULTS: Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. CONCLUSIONS: Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.

Cardiac output improvement by pecavaptan: a novel dual-acting vasopressin V1a/V2 receptor antagonist in experimental heart failure.

AIMS: Arginine vasopressin (AVP) mediates deleterious effects via vascular V1a and renal V2 receptors in heart failure (HF). Despite positive short-term decongestive effects in phase II HF studies, selective V2 receptor antagonism has shown no long-term mortality benefit, potentially related to unopposed V1a receptor activation. We compared the novel dual V1a/V2 receptor antagonist pecavaptan with the selective V2 receptor antagonist tolvaptan in pre-clinical HF models. METHODS AND RESULTS: In vitro IC50 determination in recombinant cell lines revealed similar receptor selectivity profiles (V2:V1a) of tolvaptan and pecavaptan for human and dog AVP receptors, respectively. Two canine models were used to compare haemodynamic and aquaretic effects: (i) anaesthetised dogs with tachypacing-induced HF, and (ii) conscious telemetric dogs with a non-invasive cardiac output (CO) monitor. Tolvaptan and pecavaptan exhibited no differences in urinary output. In HF dogs, pecavaptan counteracted the AVP-induced increase in afterload and decrease in CO (pecavaptan: 1.83 ± 0.31 L/min; vs. tolvaptan: 1.46 ± 0.07 L/min, P < 0.05). In conscious telemetric animals, pecavaptan led to a significant increase in CO (+0.26 ± 0.17 L/min, P = 0.0086 vs. placebo), in cardiac index (+0.58 ± 0.39 L/min/m2 , P = 0.009 vs. placebo) and a significant decrease in total peripheral resistance (-5348.6 ± 3601.3 dyn × s/cm5 , P < 0.0001 vs. placebo), whereas tolvaptan was without any significant effect. CONCLUSIONS: Simultaneous blockade of vascular V1a and renal V2 receptors efficiently induces aquaresis and counteracts AVP-mediated haemodynamic aggravation in HF models. Dual V1a/V2 antagonism may lead to improved outcomes in HF.