The skin is the largest organ of the body, providing a protective barrier against bacteria, chemicals and physical insults while maintaining homeostasis in the internal environment. Such a barrier function the skin ensures protection against excessive water loss. The skin's immune defence consists of several facets, including immediate, non-specific mechanisms (innate immunity) and delayed, stimulus-specific responses (adaptive immunity), which contribute to fending off a wide range of potentially invasive microorganisms. This article is an overview of all known data about 'fragile skin'. Fragile skin is defined as skin with lower resistance to aggressions. Fragile skin can be classified into four categories up to its origin: physiological fragile skin (age, location), pathological fragile skin (acute and chronic), circumstantial fragile skin (due to environmental extrinsic factors or intrinsic factors such as stress) and iatrogenic fragile skin. This article includes the epidemiologic data, pathologic description of fragile skin with pathophysiological bases (mechanical and immunological role of skin barrier) and clinical description of fragile skin in atopic dermatitis, in acne, in rosacea, in psoriasis, in contact dermatitis and other dermatologic pathologies. This article includes also clinical cases and differential diagnosis of fragile skin (reactive skin) in face in adult population. In conclusion, fragile skin is very frequent worldwide and its prevalence varies between 25% and 52% in Caucasian, African and Asian population. Conflicts of interests Funding sourcesNone declared. Epidemiology of fragile skinA recent publication by Haftek describes the results of recent survey realized about 'fragile skin'. Fragile skin was perceived to occur in a substantial proportion of individuals from any given country. The survey was done at 5500 people in a representative sample from the population of five countries: France, Sweden, Spain, Japan and the USA. One of the first results was that all of the respondents were able to answer the question. For them, fragile skin has a very specific meaning. The answers varied depending on the population and their phototypes. Between 25% and 30% of 'Caucasian' respondents (white Europeans), 42% of those with typically 'African' skin and 52% of those with Asian skin reported that their skin was fragile. These people are generally young (around 40% of the European sample were aged 15-34 years) and predominantly female. Fragile skin has an important link to skin pathology, as those who claim their skin is fragile are also more likely to have recently suffered a skin condition, to have acne or to have a history of atopic dermatitis (AD).Those at either end of the age spectrum (babies and elderly patients with dermatoporosis) have generally fragile skin. It can also affect people of all ages in certain areas of the body, such as the eyelids, neck, area around the mouth and areas that receive a lot of sun exposure, such as the d ecollet e or forehead. Dermatologists know th...
BackgroundIn acne, several studies report a poor adherence to treatments. We evaluate, in a real-life setting conditions, the impact of compliance to physician’s instructions, recommendations and adherence to the treatments on clinical outcome in patients with mild to moderate acne in an observational, non-interventional prospective study carried out in 72 Dermatologic Services in Spain (ACTUO Trial).MethodsSix-hundred-forty-three subjects were enrolled and 566 patients (88 %) completed the 3 study visits. Study aimed to evaluate the impact of adherence (assessed with ECOB scale) on clinical outcome, as well as how the use of specific adjuvant treatments (facial cleansing, emollient, moisturizing and lenitive specific topical products) influences treatment’s adherence and acne severity (0–5 points score). Recommendation of specific adjuvant skin barrier repair products was made in 85.2 %.ResultsOverall, clinical improvement was observed throughout follow-up visits with an increased proportion of patients who reported reductions of ≥50 % on the total number of lesions (2 months: 25.2 %; 3 months: 57.6 %) and reductions of severity scores (2.5, 2.0 and 1.3 at 1, 2 and 3 months after treatment, respectively). Adherence to treatment was associated with a significant reduction on severity grading, a lower number of lesions and a higher proportion of patients with ≥50 % improvement.ConclusionsGood adherence to medication plus adherence to adjuvants was significantly associated with a higher clinical improvement unlike those that despite adherence with medication had a low adherence to adjuvants. A good adherence to adjuvant treatment was associated with improved adherence and better treatment outcomes in mild to moderate acne patients. (ISRCTN Registry: ISRCTN14257026).
SummaryBackgroundRecessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.ObjectivesTo investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC.MethodsWe conducted RNA‐Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.ResultsInterdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB.ConclusionsOur results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development.Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix‐synthetic capacity.This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor‐β signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention.It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.
BackgroundDystrophic Epidermolysis Bullosa (DEB) is a rare genodermatosis (7 cases per million) that causes blisters and erosions with minor trauma in skin and mucosa, and other systemic complications. A recently updated systematic review showed that the research evidence about DEB therapies is poor. As new trials in DEB are difficult and expensive, it is important to prioritizise research that patients and clinicians consider more relevant.ObjectivesTo describe and prioritize the most important uncertainties about DEB treatment shared by patients, carers and health care professionals (HCPs) in order to promote research in those areas.MethodsA DEB Priority Setting Partnership (PSP) was established, including patients, carers and HCPs. DBE uncertainties were gathered from patients and clinicians, and prioritized in a transparent process, using the methodology advocated by the James Lind Alliance.ResultsIn the consultation stage, 323 uncertainties were submitted by 58 participants. Once the duplicated and non-treatment uncertainties were removed, the remainder were reduced to a list of 24 most voted questions. These 24 uncertainties were prioritized in a final workshop where a balanced number of patients, carers and HCPs selected the top 10 therapy uncertainties. The final list includes interventions in wound care, itch and pain management, treatment and prevention of syndactyly, cancer prevention and future promising therapies.ConclusionsThe final list of the top 10 treatment uncertainties on the management of DEB provides guidance for researchers and funding bodies, to ensure that future research answers questions that are important to both clinicians and patients. The method proposed by the James Lind Alliance is feasible for very rare disorders.
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