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Generalised pustular psoriasis (GPP) is a rare, chronic and life‐threatening inflammatory skin disease characterised by widespread eruption of sterile pustules. With the approval of a GPP flare treatment in several countries occurring only recently, the socioeconomic burden associated with GPP is not well established. To highlight current evidence for patient burden, healthcare resource utilization (HCRU) and costs associated with GPP. Patient burden results from serious complications including sepsis and cardiorespiratory failure causing hospitalization and death. HCRU is driven by high hospitalization rates and treatment costs. The mean duration of a GPP hospital stay ranges from 10 to 16 days. A quarter of patients require intensive care, and the mean intensive care stay is 18 days. In comparison to patients with plaque psoriasis (PsO), patients with GPP have: a 64% higher score on the Charlson Comorbidity Index; higher hospitalization rates (≤36.3% vs. ≤23.3%); lower overall quality of life, and higher symptom scores for pain, itch, fatigue, anxiety and depression; direct costs associated with treatment 1.3‐ to 4.5‐fold higher; higher rates of disabled work status (20.0% vs. 7.6%); and increased presenteeism (i.e. worse impairment at work), impaired daily activities, and medically related absenteeism. Current medical management and drug treatment utilising non‐GPP‐specific therapies impose a significant patient and direct economic burden. GPP also imposes an indirect economic burden by increasing work productivity impairment and medically related absenteeism. This high level of socioeconomic burden reinforces the need for new therapies with proven efficacy in the treatment of GPP. [ABSTRACT FROM AUTHOR]

Aims Long non-coding RNAs (lncRNAs) have been shown to regulate numerous processes in the human genome, but the function of these transcripts in vascular aging is largely unknown. We aim to characterize the expression of lncRNAs in endothelial aging and analyse the function of the highly conserved lncRNA H19. Methods and results H19 was downregulated in endothelium of aged mice. In human, atherosclerotic plaques H19 was mainly expressed by endothelial cells and H19 was significantly reduced in comparison to healthy carotid artery biopsies. Loss of H19 led to an upregulation of p16 and p21, reduced proliferation and increased senescence in vitro. Depletion of H19 in aortic rings of young mice inhibited sprouting capacity. We generated endothelial-specific inducible H19 deficient mice (H19iEC-KO), resulting in increased systolic blood pressure compared with control littermates (Ctrl). These H19iEC-KO and Ctrl mice were subjected to hindlimb ischaemia, which showed reduced capillary density in H19iEC-KO mice. Mechanistically, exon array analysis revealed an involvement of H19 in IL-6 signalling. Accordingly, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were upregulated upon H19 depletion. A luciferase reporter screen for differential transcription factor activity revealed STAT3 as being induced upon H19 depletion and repressed after H19 overexpression. Furthermore, depletion of H19 increased the phosphorylation of STAT3 at TYR705 and pharmacological inhibition of STAT3 activation abolished the effects of H19 silencing on p21 and vascular cell adhesion molecule 1 expression as well as proliferation. Conclusion These data reveal a pivotal role for the lncRNA H19 in controlling endothelial cell aging. [ABSTRACT FROM AUTHOR]