RESUMEN
SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This ï¬rst part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.
Asunto(s)
Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Italia , Fármacos Dermatológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Dermatología/normasRESUMEN
The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Italia , Dermatología/normasRESUMEN
SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inï¬ammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The ï¬rst part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/terapia , Italia , Femenino , Embarazo , Niño , Adulto , Masculino , Emolientes/uso terapéutico , Complicaciones del Embarazo/terapia , Complicaciones del Embarazo/tratamiento farmacológico , Dermatología/normasRESUMEN
This study investigates the roles of mucosal-associated invariant T (MAIT) cells and Vα7.2+/CD161- T cells in skin diseases, focusing on atopic dermatitis. MAIT cells, crucial for bridging innate and adaptive immunity, were analyzed alongside Vα7.2+/CD161- T cells in peripheral blood samples from 14 atopic dermatitis patients and 10 healthy controls. Flow cytometry and machine learning algorithms were employed for a comprehensive analysis. The results indicate a significant decrease in MAIT cells and CD69 subsets in atopic dermatitis, coupled with elevated CD38 and polyfunctional MAIT cells producing TNFα and Granzyme B (TNFα+/GzB+). Vα7.2+/CD161- T cells in atopic dermatitis exhibited a decrease in CD8 and IFNγ-producing subsets but an increase in CD38 activated and IL-22-producing subsets. These results highlight the distinctive features of MAIT cells and Vα7.2+/CD161- T cells and their different roles in the pathogenesis of atopic dermatitis and provide insights into their potential roles in immune-mediated skin diseases.
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Dermatitis Atópica , Células T Invariantes Asociadas a Mucosa , Humanos , Citometría de Flujo , Factor de Necrosis Tumoral alfa , Voluntarios SanosRESUMEN
Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.
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Síndrome de Hipersensibilidad a Medicamentos , Eosinofilia , Adulto , Humanos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/terapia , Consenso , Técnica Delphi , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Eosinofilia/terapia , Encuestas y CuestionariosRESUMEN
Atopic dermatitis is an inflammatory skin disease characterized by significant permeability barrier damage. Regulation and maintenance of permeability and antimicrobial skin barriers are strongly connected. There is a lack of comprehensive studies of the expression of all 5 major antimicrobial peptide functional groups in atopic dermatitis. The aim of this study was to investigate the major antimicrobial peptide functional groups in lesional atopic dermatitis, non-lesional atopic dermatitis, and healthy control samples, using real-time quantitative PCR and immunohistochemistry. Lesional psoriatic skin was also examined as a diseased control. No differences in mRNA levels were detected between non-lesional atopic dermatitis and healthy control skin, and, at the protein level, the only change was the significantly decreased LL-37 in non-lesional atopic dermatitis. In lesional atopic dermatitis, several antimicrobial peptides were significantly altered at the mRNA level, while, at the protein level, all antimicrobial peptides were significantly upregulated or unchanged, except for LL-37, which decreased, compared with healthy controls. Antimicrobial peptides were similarly elevated in lesional atopic dermatitis and lesional psoriatic skin, with somewhat higher expression in lesional psoriatic skin, except for LL-37. In conclusion, LL-37 was the only antimicrobial peptide that was impaired in both non-lesional and lesional atopic dermatitis, highlighting its potential pathogenetic or exacerbating role in the initial stages of the disease.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/diagnóstico , Piel , Péptidos Antimicrobianos , Estado de Salud , ARN MensajeroRESUMEN
Recent data indicate that distinct skin areas show different microbial/chemical milieu. Keratinocytes (KC) respond to these stimuli by producing cytokine mediators. Therefore, we aimed to determine KC-derived cytokine expression in distinct healthy skin regions (gland-poor [GP], sebaceous gland-rich [SGR] and apocrine gland-rich [AGR]), and their changes in skin diseases of the given regions (atopic dermatitis [AD], papulopustular rosacea [PPR] and psoriasis). Cytokines were analysed at the mRNA and protein levels, and literature analysis was performed for functional categorization. The three regions showed characteristically different cytokine patterns. GP was featured by an IL-25/IL-33/IL-36RA/IL-38/IL-18 cytokine milieu, SGR was characterized by IL-23/IL-17C/IL-18, and AGR skin exhibited a mixed IL-25/IL-33/IL-23/IL-18 profile. Literature analyses revealed different homeostatic and proinflammatory roles of these cytokine patterns (Th2 related in GP, Th17 related in SGR and mixed Th2/Th17 in AGR). In skin diseases which are primarily epidermal cytokine-driven (AD, PPR), the level of the regionally characteristic cytokines were further elevated, in contrast to the autoantigen-driven psoriasis, where the cytokine pattern was independent from the localization. Healthy skin regions are equipped with different KC-derived cytokine profiles, which may influence each region's capability of mediator production in certain types of dermatoses.
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Dermatitis Atópica , Psoriasis , Rosácea , Humanos , Interleucina-18/metabolismo , Interleucina-33/metabolismo , Epidermis/metabolismo , Queratinocitos/metabolismo , Psoriasis/metabolismo , Citocinas/metabolismo , Inflamación/metabolismo , Dermatitis Atópica/metabolismo , Rosácea/metabolismo , Interleucina-23/metabolismo , Interleucinas/metabolismoRESUMEN
BACKGROUND: Intestinal symptoms are common in patients with hidradenitis suppurativa (HS). HS patients may experience a broad spectrum of chronic inflammatory intestinal disorders (CIID), not exclusive to inflammatory bowel diseases, which are diagnosed by colonoscopy and intestinal biopsies. The frequency of CIID in patients with HS has not been investigated. OBJECTIVE: The objectives of this study were to determine the occurrence of CIID in HS and characterize this clinical population. Furthermore, the feasibility of using faecal calprotectin (FC) test or anti-Saccharomyces cerevisiae antibody (ASCA) levels to assess the colonic inflammation of CIID in HS patients was investigated. METHODS: All newly diagnosed and untreated HS patients (n = 74) were referred to a gastroenterologist for FC followed by colonoscopy after informed consent. C-reactive protein (CRP), white blood cell count, nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) polymorphism, and ASCA levels were measured. Patients were divided into HS-only and HS with CIID (HS + CIID) groups, based on the absence or presence of CIID. Laboratory and clinical parameters (age, gender, HS onset, clinical stage, family history, body mass index (BMI), smoking) were compared between the groups. RESULTS: Thirteen patients complained gastrointestinal symptoms prior to any examination, including 11 in the HS + CIID group. The CIID frequency in HS was 28.4% (n = 21/74), based on colonoscopy and histology. Significantly more patients had severe disease state in the HS + CIID group compared with the HS-only group, and BMI was significantly lower in the HS + CIID group (28.20 ± 5.58 vs. 32.74 ± 6.45, p = 0.006). FC positivity occurred significantly more in HS + CIID patients compared with HS-only patients (90.48% vs. 3.77%, p < 0.001), and ASCA IgG levels were significantly elevated in HS + CIID patients (22.08 ± 23.07 vs. 8.41 ± 10.94 U/mL, p = 0.001). The FC test identified HS + CIID patients with 96.23% specificity and 91.3% sensitivity, while ASCA displayed 77.8% sensitivity and 76.3% specificity. Blood count, CRP, and the presence of NOD2 polymorphisms were indifferent between the two groups. CONCLUSION: A high frequency of CIID was detected in the examined HS population. The noninvasive FC test has high sensitivity and specificity for diagnosing CIID in HS patients. Concomitant CIID and HS may indicate the need for an early-start for biological treatment.
Asunto(s)
Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/tratamiento farmacológico , Fumar , Proteína C-Reactiva/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.
RESUMEN
As a contact sport, wrestling may result in injuries. Based on the severity, they are classified as mild, moderate, severe and critical. All injuries occurring at international competitions are documented in a cloud-based surveillance system. The purpose of this study was to analyze the incidence and characteristics of moderate and severe (including critical) wrestling injuries that occurred during five international Olympic-style wrestling competitions in 2016-2019. Three Wrestling World Championships and two European Wrestling tournaments were organized by the Hungarian Wrestling Federation in 2016-2019. A total of 2483 wrestlers in three Olympic wrestling styles have competed in 3007 matches. Data from all injuries were recorded and analyzed to define rates, locations, types and severity, and to compare with previous reports. A total of 53 wrestlers sustained 55 injuries, which is equivalent to an overall injury incidence rate of 9.1 (9.1/1000 athletic exposures). Greco-Roman and Women Wrestling had the same injury incidence rate, while Freestyle had a lower one (9.5 versus 8.5). The injury proportion by regions and anatomic locations were on head and face 29.1%, spine and trunk 16.4 % and the upper-and-lower extremity injuries equally 27.3%. The most common types of injuries included ligament lesions, joint injuries, skin lacerations, and contusions. Five wrestlers (0.8) sustained strangulation or concussion. Wrestling injury rates during United World Wrestling competitions are not high, but when happen they can be serious. Despite relatively low incidence rate of injuries, there is a need for continuous education for medical teams, referees and coaches to avoid wrestling injuries.
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Traumatismos en Atletas , Conmoción Encefálica , Deportes , Lucha , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología , Femenino , Humanos , Torso/lesiones , Lucha/lesionesRESUMEN
This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
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Angioedema , Asma , Urticaria , Angioedema/diagnóstico , Angioedema/etiología , Angioedema/terapia , Enfermedad Crónica , Humanos , Prevalencia , Calidad de Vida , Urticaria/diagnóstico , Urticaria/epidemiología , Urticaria/etiologíaRESUMEN
BACKGROUND: Hidradenitis suppurativa (HS) is a, chronic skin disease affecting up to 1% of the population in Europe. This study aims to assess the cost-of-illness of HS from a societal perspective in Hungary and to analyze the predictors of costs. METHODS: A multicentre, cross-sectional cost-of-illness study was performed among 200 adult HS patients. We evaluated direct medical (physician consultations, inpatient admissions, medical, and surgeries), direct non-medical (transportation and caregiving), and indirect costs (productivity loss). RESULTS: The mean annual cost-of-illness of HS was 6,791 per patient. The main cost components were productivity loss (53.3%), biological treatment (21.5%), and informal care (9.2%). Patients missed, on average, 26 and 63 days from work annually due to absenteeism and presenteeism, respectively. Male sex, more severe disease, gluteal involvement, and coexisting inflammatory bowel disease were associated with higher direct medical costs, while lower education level and worse quality-of-life outcomes predicted higher indirect costs. CONCLUSION: This is the first study to assess both direct and indirect costs in HS patients. HS imposes a substantial burden on patients and society, predominantly arising from productivity loss and biological therapy. Resource utilization data and cost-of-illness estimates provide valuable inputs into cost-effectiveness analyses of health interventions in HS.
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Hidradenitis Supurativa , Absentismo , Adulto , Costo de Enfermedad , Estudios Transversales , Eficiencia , Femenino , Costos de la Atención en Salud , Hidradenitis Supurativa/terapia , Humanos , MasculinoRESUMEN
The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to compare the major permeability barrier components (stratum corneum and tight junction (TJ)), investigate the distribution of (corneo)desmosomes and TJs, and measure barrier function in healthy sebaceous gland-rich (SGR), apocrine gland-rich (AGR), and gland-poor (GP) skin regions. Molecules involved in cornified envelope (CE) formation, desquamation, and (corneo)desmosome and TJ organization were investigated at the mRNA and protein levels using qRT-PCR and immunohistochemistry. The distribution of junction structures was visualized using confocal microscopy. Transepidermal water loss (TEWL) functional measurements were also performed. CE intracellular structural components were similarly expressed in gland-rich (SGR and AGR) and GP areas. In contrast, significantly lower extracellular protein levels of (corneo)desmosomes (DSG1 and CDSN) and TJs (OCLN and CLDN1) were detected in SGR/AGR areas compared to GP areas. In parallel, kallikrein proteases were significantly higher in gland-rich regions. Moreover, gland-rich areas were characterized by prominently disorganized junction structures ((corneo)desmosomes and TJs) and significantly higher TEWL levels compared to GP skin, which exhibited a regular distribution of junction structures. According to our findings, the permeability barrier of our skin is not uniform. Gland-rich areas are characterized by weaker permeability barrier features compared with GP regions. These findings have important clinical relevance and may explain the preferred localization of acantholytic skin diseases on gland-rich skin regions (e.g., Pemphigus foliaceus, Darier's disease, and Hailey-Hailey disease).
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Acantólisis/metabolismo , Epidermis/metabolismo , Glándulas Sebáceas/metabolismo , Uniones Estrechas/metabolismo , Acantólisis/patología , Adulto , Anciano , Epidermis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Permeabilidad , Glándulas Sebáceas/patología , Uniones Estrechas/patologíaRESUMEN
Alcohol affects the symptoms, compliance and comorbidities as well as the safety and efficacy of treatments in psoriatic patients. In this review, we aim to summarize and link clinical observations with a molecular background, such as signaling pathways at the cellular level and genetic variations, and to provide an overview of how this knowledge could influence our treatment selection and patient management.
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Etanol/efectos adversos , Psoriasis/patología , Investigación Biomédica Traslacional , Animales , Predisposición Genética a la Enfermedad , Humanos , Modelos Biológicos , Cooperación del Paciente , Psoriasis/genética , Psoriasis/terapiaRESUMEN
Antimicrobial and immunomodulatory peptides (AMPs) are considered as the key players in the maintenance of skin barrier functions. Here, we developed a novel approach for the examination of AMPs in the outermost layer of the epidermis, namely stratum corneum (SC). The SC sample collection by tape stripping was coupled with detection by highly specific and sensitive parallel reaction monitoring (PRM)-based mass spectrometry. We found that hexane-free processing of SC samples produced higher protein yield compared to hexane-based extraction. Of the 18 investigated peptides, 9 could be detected either in healthy or in inflamed skin specimens. Regarding the amount of S100A8, LCN2, LACRT and LYZ significant topographical differences were described among gland poor (GP), sebaceous gland rich (SGR) and apocrine gland rich (AGR) healthy skin regions. We applied a minimally invasive, reproducible approach for sampling, which can be assessed for research and diagnostic purposes and for monitoring the effectiveness of therapies in skin diseases.
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Epidermis/metabolismo , Espectrometría de Masas/métodos , Proteínas Citotóxicas Formadoras de Poros/análisis , Adenosina Trifosfato/metabolismo , Humanos , Piel/metabolismoRESUMEN
PURPOSE: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects up to 1% of the population in Europe. The EQ-5D is the most commonly used generic instrument for measuring health-related quality of life among HS patients. This study aims to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with HS. METHODS: We recruited 200 consecutive patients with HS (mean age 37 years, 38% severe or very severe HS) to participate in a multicentre cross-sectional survey. Patients completed the EQ-5D-3L, EQ-5D-5L, Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires. RESULTS: More than twice as many different health state profiles occurred in the EQ-5D-5L compared to the EQ-5D-3L (101 vs. 43). A significant reduction in ceiling effect was found for the mobility, self-care and usual activities dimensions. A good agreement was established between the EQ-5D-3L and EQ-5D-5L with an intraclass correlation coefficient of 0.872 (95% CI 0.830-0.903; p < 0.001) that was confirmed by a Bland-Altman plot. EQ-5D-5L improved both the absolute and relative informativity in all dimensions except for anxiety/depression. EQ-5D-3L and EQ-5D-5L demonstrated similar convergent validity with DLQI and Skindex-16. EQ-5D-5L was able to better discriminate between known groups of patients based on the number of comorbidities and disease severity (HS-Physician's Global Assessment). CONCLUSION: In patients with HS, the EQ-5D-5L outperformed the EQ-5D-3L in feasibility, ceiling effects, informativity and known-groups validity for many important clinical characteristics. We recommend using the EQ-5D-5L in HS patients across various settings, including clinical care, research and economic evaluations.
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Hidradenitis Supurativa/psicología , Psicometría/métodos , Calidad de Vida/psicología , Adulto , Femenino , Humanos , MasculinoRESUMEN
Rosacea is a common chronic inflammation of sebaceous gland-rich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of patients with rosacea. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea samples compared with healthy sebaceous gland-rich skin, using RNA sequencing analysis (n = 8). Pathway analyses by Cytoscape ClueGO revealed 15 significantly enriched pathways related to skin barrier formation. RT-PCR and immunohistochemistry were used to validate the pathway analyses. The results showed significant alterations in barrier components in papulopustular rosacea samples compared with sebaceous gland-rich skin, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in papulopustular rosacea was unexpectedly similar to atopic dermatitis; this similarity was confirmed by immunofluorescent staining. In summary, besides the well-known dysregulation of immunological, vascular, and neurological functions, we demonstrated prominent permeability barrier alterations in papulopustular rosacea at the molecular level, which highlight the importance of barrier repair therapies for rosacea.
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Rosácea/metabolismo , Piel/metabolismo , Proteínas de Unión al ADN , Desmosomas/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Calicreínas/genética , Permeabilidad , Análisis de Componente Principal , RNA-Seq , Transducción de Señal , Piel/citología , Uniones Estrechas/fisiologíaRESUMEN
The immunological barrier of the healthy skin is considered to be unified on the whole body surface-however, recent indirect findings have challenged this dogma since microbial and chemical milieu (e.g., sebum, sweat, and pH) exhibit remarkable differences on topographically distinct skin areas. Therefore, in the present study, we performed whole transcriptomic and subsequent pathway analyses to assess differences between sebaceous gland rich (SGR) and sebaceous gland poor (SGP) regions. Here, we provide the first evidence that different skin regions exhibit a characteristic innate and adaptive immune and barrier milieu as we could detect significantly increased chemokine (CCL2, 3, 19, 20, 23, 24) and antimicrobial peptide (S100A7, A8, A9, lipocalin, ß-defensin-2) expression, altered barrier (keratin 17, 79) functions, and a non-inflammatory Th17/IL-17 dominance in SGR skin compared to SGP. Regarding pro-inflammatory molecules (IL-1α, IL-6, IL-8, IL-33, TNF-α), similarly low levels were detected in both regions. Our data may explain the characteristic topographical localization of some immune-mediated and autoimmune skin disorders and we also propose that the term "healthy skin control sample," widely used in experimental Dermatology, should only be accepted if researchers carefully specify the exact region of the healthy skin (along with the site of the diseased sample).
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Glándulas Sebáceas/fisiología , Piel/inmunología , Células Th17/inmunología , Inmunidad Adaptativa , Adulto , Anciano , Anciano de 80 o más Años , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Femenino , Voluntarios Sanos , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Queratina-17/metabolismo , Masculino , Persona de Mediana Edad , Mapas de Interacción de Proteínas , Transducción de Señal , Secuenciación del ExomaRESUMEN
Psoriasis is a common inflammatory skin disease and dendritic cells (DCs) play crucial role in the development of skin inflammation. Although the characteristics of skin DCs in psoriasis are well defined, less is known about their peripheral blood precursors. Our aim was to characterize the phenotypic features as well as the cytokine and chemokine production of CD1c+ myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the blood samples of psoriatic patients. Blood DCs were isolated by using a magnetic separation kit, and their intracytoplasmic cytokine production and CD83/CD86 maturation/activation marker expression were investigated by 8-colour flow cytometry. In CD1c+ mDCs the intracellular productions of Th1, Th2, Th17, Th22 and Treg polarizing cytokines were examined simultaneously, whereas in pDCs the amounts of IFNα as well as IL-12, IL-23 and IL-6 were investigated. The chemokine production of both DC populations was investigated by flow-cytometry and ELISA. According to our results psoriatic CD1c+ mDCs were in a premature state since their CD83/CD86 maturation/activation marker expression, IL-12 cytokine, CXCL9 and CCL20 chemokine production was significantly higher compared to control cells. On the other hand, blood pDCs neither produced any of the investigated cytokines and chemokines nor expressed CD83/CD86 maturation/activation markers. Our results indicate that in psoriasis not only skin but also blood mDCs perform Th1 polarizing and Th1/Th17 recruiting capacity, while pDCs function only in the skin milieu.