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Background: Chronic inflammatory skin diseases (CISDs) are among the most common diseases in the Western world. Current estimates of medical care for CISDs are primarily based on surveys among patients in medical care facilities and on health insurance data. Aim: Survey-based examination to what extent CISD patients in health-aware environment consider their skin disease to be controlled. Methods: The survey of CISD patients was carried out in 2022 among the employees of a pharmaceutical company located in Germany and Switzerland. Software-based, anonymous, self-reported questionnaires were used. Results: The number of employees, who answered the questionnaire, was 905. Of these, 222 participants (24.5%) reported having at least one CISD. 28.7% of participants with CISD described their disease as being hardly or not controlled. Regarding the nature of disease, more than one third of participants suffering from hidradenitis suppurativa (HS) or psoriasis fell into the hardly/not controlled category. In contrast, the largest proportion of participants with chronic spontaneous urticaria (43%) or atopic dermatitis (42%) considered their CISD to be completely or well controlled. Only 35.5% of CISD sufferers stated that they were currently under medical care for their skin condition. Being under medical care, however, had no influence on the extent CISD sufferers considered their skin disease to be controlled. The number of active CISD episodes but not the total number of symptomatic days per year was negatively associated with poor disease control (p = 0.042 and p = 0.856, respectively). Poor disease control had a negative effect on the personal and professional lives of those affected, as deduced from its positive association with the extent of daily activity impairment and presenteeism (p = 0.005 and p = 0.005, respectively). Moreover, 41.4 and 20.7% of participants with hardly/not controlled disease stated that their CISD had a moderate and severe or very severe impact on their overall lives (p < 0.001), respectively. A severe or very severe impact of their CISD on their overall life was most commonly reported by participants with HS. Conclusion: Medical care for CISDs, even in an environment with high socio-economic standard and high health-awareness, still appears to be limited and has a negative impact on individuals and society.
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Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development.
RESUMO
BACKGROUND: Acute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. RESULTS: The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA < 30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity = 76.5%, specificity = 88.9%). CONCLUSIONS: The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information. TRIAL REGISTRATION: ClinicalTrials.gov NCT00724022 . Retrospectively registered July 2008.