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INTRODUCTION: Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening skin condition characterized by flares comprising widespread sterile pustules and systemic inflammation. Both the rarity and heterogeneity of the disease have made GPP classification and standardization of clinical criteria challenging. Before the approval of spesolimab (IL-36R antibody) in 2022, there were no approved treatments in the USA or Europe for GPP flares. Treatment for GPP has amounted to off-label use of medicines approved to treat plaque psoriasis. Our aim was to describe the sociodemographics, clinical characteristics, and treatment patterns of patients with GPP in Spain. METHODS: Non-interventional, descriptive, multi-center, retrospective chart review of patients diagnosed with GPP in Spain. RESULTS: 56 patients (50% women) were included, with a mean (standard deviation, SD) age at diagnosis of 53.7 (20.5) and a mean (SD) time of follow-up of 3.7 (3.1) years. In 80% of patients, GPP diagnosis was associated with a flare and 67.3% had known risk factors for GPP (such as previous diagnosis or family history of plaque psoriasis, comorbidities, smoking or stress). Hypertension and plaque psoriasis were the most frequent comorbidities (44.6% each). The number of GPP flares per patient-year was 0.55 with (range 0-4) a mean (SD) body surface area involvement of 21.3% (19.1). The most frequent manifestations of GPP flares were pustules (88.5%), erythema (76.9%), and scaling (76.9%). Additionally, 65.4% of patients had plaque psoriasis, 53.8% had unspecified skin lesions, and 30.8% experienced pain. The treatments used for GPP flares were off-label conventional systemic drugs (75%), mostly corticosteroids, cyclosporine, and acitretin. In the periods between flares, off-label biologics were used in 56.5% of patients. During the study period, 9 patients (16.1%) had at least one complication and 5 of them required hospitalization. CONCLUSION: This is the first multicenter study in Spanish GPP patients. Most patients were in their fifties, with personal or family history of plaque psoriasis, stress, smoking and a wide range of comorbidities and complications. Even though the number of flares per patient/year was 0.55, there was variability between patients. Both off-label conventional systemics and off-label biologics were used for flare management without a clear treatment pattern.
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BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.
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Development of periungual pyogenic granulomas (pPGs) has been associated with several systemic treatments, including retinoids, taxanes, epidermal growth factor receptor inhibitors, and vascular endothelial growth factor inhibitors. We present the case of an 8-year-old girl with a personal history of acute myelomonocytic leukemia treated with a haploidentical hematopoietic stem cell transplant who developed pPGs 2 months after starting ravulizumab. Ravulizumab is a monoclonal antibody directed against C5 protein. No previous reports of pPGs development have been described with ravulizumab.
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PURPOSE: The healthcare industry is a significant contributor to single-use plastic waste, particularly in the operating room (OR). This study aims to assess the volume of plastic waste generated during total hip, knee, and shoulder arthroplasty in the OR and identify areas for improvement. METHOD: A prospective transversal study at a tertiary hospital was conducted. All total knee arthroplasty (TKA), total hip arthroplasty (THA), and reverse shoulder arthroplasty (RSA) from April to July 2021 were included. The weight of plastic used during patient preparation, anaesthesia, and the surgical procedure was recorded. To calculate the environmental impact, a calculator generated by the United States Environmental Protection Agency (U.S. EPA) was used. RESULTS: A total of 68 surgeries were included. The mean weight of plastic used in total was 7.3 kg (SD 0.48), with the highest yielding procedure being TKA. It generated a mean of 7.63 kg (SD 0.28), followed by THA at 7.28 kg (SD 0.43), and RSA at 6.87 kg (SD 0.47). Various scenarios were simulated to evaluate the potential impact of reducing plastic waste. Substituting plastic wrapping with recyclable materials could save 159.6 kg of CO2 emissions per 100 prostheses. Eliminating non-essential equipment and adopting reusable fabric drapes also showed a significant potential. CONCLUSION: The findings highlight the need for environmentally sustainable practices in the OR. In this way, the healthcare sector can contribute to a cleaner and greener world without compromising patient safety.
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Salas Cirúrgicas , Plásticos , Humanos , Estudos Prospectivos , Estudos Transversais , Reciclagem/métodos , Resíduos de Serviços de Saúde/estatística & dados numéricos , Procedimentos Ortopédicos/métodosRESUMO
Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions that significantly impact the quality of life of patients, with diverse treatment options available. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37, in Th1, Th2, and Th17 inflammatory responses, closely associated with the pathogenesis of psoriasis and atopic dermatitis. Hence, IL-18 and IL-37 could potentially become therapeutic targets. This narrative review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to 30 May 2024, underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still's Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis.
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Dermatite Atópica , Interleucina-18 , Interleucina-1 , Psoríase , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/metabolismo , Interleucina-18/metabolismo , Interleucina-1/metabolismo , Interleucina-1/antagonistas & inibidores , Animais , Terapia de Alvo MolecularRESUMO
Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in industrialized societies, influenced by both environmental changes and a genetic predisposition. However, the exact immune factors driving these chronic, progressive diseases are not fully understood. By using multi-omics techniques in cutaneous IMIDs, it is expected to advance the understanding of skin biology, uncover the underlying mechanisms of skin conditions, and potentially devise precise and personalized approaches to diagnosis and treatment. We provide a narrative review of the current knowledge in genomics, epigenomics, and proteomics of atopic dermatitis and psoriasis. A literature search was performed for articles published until 30 November 2023. Although there is still much to uncover, recent evidence has already provided valuable insights, such as proteomic profiles that permit differentiating psoriasis from mycosis fungoides and ß-defensin 2 correlation to PASI and its drop due to secukinumab first injection, among others.
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Dermatite Atópica , Psoríase , Neoplasias Cutâneas , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/genética , Multiômica , Proteômica , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/genética , Agentes de ImunomodulaçãoRESUMO
BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Psoríase/diagnóstico por imagem , Unhas , Fatores de Risco , Europa (Continente)RESUMO
A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.
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Psoríase , Humanos , Psoríase/etiologia , Pele , Doença Aguda , Doença CrônicaRESUMO
BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.
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COVID-19 , Psoríase , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Ansiedade/epidemiologia , Ansiedade/psicologia , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Depressão/epidemiologiaRESUMO
BACKGROUND: Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. OBJECTIVE: To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. METHODS: LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150 mg every 12 weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304 weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256 weeks. RESULTS: Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. LIMITATIONS: Open-label study with no placebo or active-comparator group. CONCLUSIONS: Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy.
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Psoríase , Adulto , Humanos , Doença Crônica , Método Duplo-Cego , Seguimentos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.
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Doenças Cardiovasculares , Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Médicos de Atenção Primária , Psoríase , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Reumatologistas , Dermatologistas , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Prescrições , Hábitos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. OBJECTIVES: Conduct a Delphi panel study to identify current evidence and gain advanced insights into GPP. METHODS: A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%. RESULTS: Twenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the 'clinical course and flare definition', 'diagnosis', 'treatment goals' and 'holistic management of GPP' domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. CONCLUSIONS: Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice.
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Objetivos , Psoríase , Humanos , Consenso , Técnica Delphi , Psoríase/terapia , Psoríase/tratamento farmacológico , Gerenciamento Clínico , Progressão da DoençaRESUMO
BACKGROUND: Tildrakizumab (TIL) is an interleukin (IL)-23p19 inhibitor for the treatment of moderate-to-severe plaque psoriasis with long-term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed. OBJECTIVES: The TRIBUTE study (open-label, Phase IV) assessed the efficacy and impact on health-related quality of life (HRQoL) of TIL 100 mg in adult moderate-to-severe psoriasis patients (naïve to IL-23/Th17 pathway inhibitors) in conditions similar to clinical practice. METHODS: Key efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex-16. Additional patient-reported outcomes included Pain-, Pruritus- and Scaling-Numerical Rating Scale (NRS), Medical Outcome Study (MOS)-Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: One hundred and seventy-seven patients were enrolled (six patients did not complete the study). After 24 weeks, the proportion of patients achieving PASI scores ≤ 3, PASI 75, PASI 90 and DLQI 0/1 was 88.4%, 92.5%, 74.0% and 70.4%, respectively. Skindex-16 overall score improved (mean absolute change from baseline, MACB [95%CI]: -53.3 [-58.1, -48.5]). Significant benefits (MACB [95%CI]) were found on pruritus-, pain- and scaling-NRS scores (-5.7 [-6.1, -5.2], -3.5 [-4.1, -3.0] and -5.7 [-6.2, -5.2], respectively), MOS-Sleep (-10.4 [-13.3, -7.4] Sleep problems Index II) and WPAI (-36.4 [-42.6, -30.2] activity impairment, -28.2 [-34.7, -21.7] productivity loss, -27.0 [-32.9, -21.1] presenteeism and -6.8 [-12.1, -1.5] absenteeism). 82.7% of patients reported PBI ≥ 3 and the mean (SD) global TSQM score was high (80.5 [18.5]). Only one serious treatment-emergent adverse event was reported (not-related to TIL). CONCLUSIONS: TIL 100 mg treatment after 24 weeks in conditions close to real clinical practice showed a quick and high improvement in psoriasis signs and HRQoL. Patient reported improvements in sleep outcomes and work productivity, relevant benefits and high treatment satisfaction. The safety profile was favourable and consistent with Phase III trials.
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Anticorpos Monoclonais , Psoríase , Adulto , Humanos , Anticorpos Monoclonais/uso terapêutico , Qualidade de Vida , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Prurido/etiologia , Prurido/induzido quimicamente , Resultado do Tratamento , Sono , Dor/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The objective of this study was to determine the minimum number of cultures needed to detect Cutibacterium acnes in primary reverse shoulder arthroplasties (RSAs). METHODS: It is a prospective study including 160 primary RSAs. Exclusion criteria included an active infection, an invasive shoulder treatment in the last 6 months before surgery, an Arthro-SCAN or Arthro-MRI in the last 6 months before surgery, previous shoulder surgeries and revision cases. In 90 cases, 11 cultures were obtained. Another 10 cultures were obtained in the other 70 cases (culture 10 was a sterile sponge to detect false positives). To determine the minimum number of cultures needed to detect C acnes, the prevalence of C acnes contamination of the 160 patients included was determined. RESULTS: There were 128 females and 32 males, with a mean age of 74 years. There were 1690 cultures obtained from the 160 primary RSA surgeries, and 132 of them turned out to be positive for C acnes. There were 42 patients with positive cultures. Twenty of them were males and 22 females. When considering the skin and the deep tissue cultures altogether, the prevalence of positive cultures for C acnes was of 26.25%. If only deep tissues cultures were considered, the prevalence of positive cultures for C acnes was of 23.13%. When considering the skin and the deep tissue cultures together, the sensitivity to detect the C acnes is 19% if only 1 culture is obtained, 31% if 2 cultures are obtained, 50% if 3 cultures are obtained, 59.5% if 4 cultures are obtained, 66.7% if 5 cultures are obtained, 73.8% if 6 cultures are obtained, 85.7% if 7 cultures are obtained, and 92.9% if 8 cultures are obtained. When considering only the deep tissue cultures, if only 1 culture is obtained, the sensitivity to detect the C acnes is 24.3%, 40.5% if 2 cultures are obtained, 54.1% if 3 cultures are obtained, 73% if 4 cultures are obtained, 89.2% if 5 cultures are obtained, and 97.3% if 6 or 7 cultures are obtained. DISCUSSION: A minimum number of 8 cultures are needed to detect C acnes in skin. Moreover, a minimum of 6 cultures are needed to detect it in deep tissues when performing an RSA.
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Artroplastia do Ombro , Infecções por Bactérias Gram-Positivas , Articulação do Ombro , Masculino , Feminino , Humanos , Idoso , Estudos Prospectivos , Articulação do Ombro/cirurgia , Articulação do Ombro/microbiologia , Propionibacterium acnes , Artroplastia , Ombro/cirurgia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologiaRESUMO
The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in host defence against microbial organisms and the development of inflammatory diseases, including psoriasis (PsO), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). IL-17A is the signature cytokine produced by T helper 17 (Th17) cells and is considered the most biologically active form. The pathogenetic involvement of IL-17A in these conditions has been confirmed, and its blockade with biological agents has provided a highly effective therapeutical approach. IL-17F is also overexpressed in the skin and synovial tissues of patients with these diseases, and recent studies suggest its involvement in promoting inflammation and tissue damage in axSpA and PsA. The simultaneous targeting of IL-17A and IL-17F by dual inhibitors and bispecific antibodies may improve the management of Pso, PsA, and axSpA, as demonstrated in the pivotal studies of dual specific antibodies such as bimekizumab. The present review focuses on the role of IL-17F and its therapeutic blockade in axSpA and PsA.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Interleucina-17 , Psoríase/tratamento farmacológico , Inflamação , Pele , Citocinas/uso terapêuticoRESUMO
Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA-positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons.
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Vírus da Hepatite E , Hepatite E , Doadores de Sangue , Seleção do Doador , Anticorpos Anti-Hepatite , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Humanos , RNA Viral , Estudos Soroepidemiológicos , Espanha/epidemiologiaRESUMO
PURPOSE OF REVIEW: Psoriasis vulgaris is the commonest presentation of psoriatic disease, but morphologic variants such as pustular psoriasis (PP) and a closely related disease, pityriasis rubra pilaris (PRP), have been known for a long time, have been associated with rheumatologic manifestations indistinguishable from psoriatic arthritis (PsA) that may go unrecognized, and often represent a therapeutic conundrum. There is recent evidence that underlying genetic and pathogenetic differences may provide the basis for newer therapeutic approaches. RECENT FINDINGS: This narrative review highlights the clinical, genetic and pathogenetic characteristics of PP and PRP, their association with PsA and recent developments in their treatment, especially with biologic agents targeting IL-36 and other cytokines of pathogenic relevance. SUMMARY: The clinical manifestations of PP and PRP are less well known to rheumatologists than those of psoriasis, and recent advances in our insight on their pathogenesis may eventually overcome the therapeutic difficulties faced by dermatologists and rheumatologists in the management of these diseases and their rheumatologic manifestations.
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Artrite Psoriásica , Artrite Reumatoide , Pitiríase Rubra Pilar , Psoríase , Artrite Psoriásica/etiologia , Artrite Psoriásica/genética , Humanos , Fenótipo , Pitiríase Rubra Pilar/genética , Pitiríase Rubra Pilar/patologia , Psoríase/genética , Psoríase/terapiaRESUMO
BACKGROUND: Despite most controlled trials have shown no measurable benefit of COVID-19 convalescent plasma (CCP) in patients with COVID-19, some studies suggest that early administration of CCP with high-titer anti-SARS-CoV-2 can be beneficial in selected patients. We investigated the efficacy of early administration of high-titer CCP to patients with COVID-19 who required hospitalization, STUDY DESIGN AND METHODS: Observational, propensity score (PS) matched case-control study of COVID-19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti-SARS-CoV-2 sample-to-cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high-standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. RESULTS: A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56-79), and 953 (60%) were men. Presenting factors independently associated with higher 30-day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d-dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30-day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91-0.98; p = .001) that extended to the 60th day after COVID-19 diagnosis (OR: 0.95; 95% CI: 0.92-0.99; p = .01). CONCLUSION: Our results suggest that CCP can still be helpful in selected patients with COVID-19 and call for further studies before withdrawing CCP from the COVID-19 therapeutic armamentarium.
Assuntos
COVID-19 , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Teste para COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Imunização Passiva , Masculino , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.
Assuntos
Interleucina-17 , Psoríase , Humanos , Interleucina-23 , Psoríase/tratamento farmacológico , Pele/patologia , Células Th17RESUMO
In the original publication [...].