RESUMO
The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03-05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease.
Assuntos
Anti-Infecciosos/uso terapêutico , Procedimentos Cirúrgicos Dermatológicos , Hidradenite Supurativa/etiologia , Hidradenite Supurativa/terapia , Anti-Inflamatórios/uso terapêutico , Pesquisa Biomédica , Comorbidade , Hidradenite Supurativa/diagnóstico por imagem , Hidradenite Supurativa/epidemiologia , Humanos , Incidência , Qualidade de Vida , Fator de Necrose Tumoral alfa/antagonistas & inibidores , UltrassonografiaAssuntos
Alergia e Imunologia/história , Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Animais , História do Século XX , Camundongos , Timócitos/citologia , Timócitos/imunologia , Timo/citologia , Timo/imunologia , Transcrição GênicaRESUMO
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.
RESUMO
Increased Type I IFNs or IFN-I have been associated with human systemic lupus erythematosus. Interestingly augmenting or negating IFN-I activity in murine lupus not only modulates systemic autoimmunity, but also impacts lupus nephritis, suggesting that IFN-I may be acting at the level of the end-organ. We find resident renal cells to be a dominant source of IFN-I in an experimental model of autoantibody-induced nephritis. In this model, augmenting IFN-I amplified antibody-triggered nephritis, whereas ablating IFN-I activity ameliorated disease. One mechanism through which increased IFN-I drives immune-mediated nephritis might be operative through increased recruitment of inflammatory monocytes and neutrophils, though this hypothesis needs further validation. Collectively, these studies indicate that an important contribution of IFN-I toward the disease pathology seen in systemic autoimmunity may be exercised at the level of the end-organ.
Assuntos
Citocinas/imunologia , Glomerulonefrite/imunologia , Interferon Tipo I/imunologia , Falência Renal Crônica/imunologia , Receptor de Interferon alfa e beta/imunologia , Animais , Antivirais/imunologia , Antivirais/farmacologia , Autoanticorpos/sangue , Autoanticorpos/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Glomerulonefrite/metabolismo , Humanos , Interferon Tipo I/farmacologia , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Falência Renal Crônica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Proteínas RecombinantesRESUMO
BACKGROUND: Atopic dermatitis (AD) is a common, chronic skin disorder often beginning in infancy. Skin barrier dysfunction early in life serves as a central event in the pathogenesis of AD. In infants at high risk of developing AD, preventative application of lipid-rich emollients may reduce the risk of developing AD. This study aims to measure the effectiveness of this intervention in a population not selected for risk via a pragmatic, randomized, physician-blinded trial in the primary care setting. METHODS: Infant-parent dyads are recruited from a primary care practice participating through one of four practice-based research networks in Oregon, Colorado, Wisconsin, and North Carolina. Eligible dyads are randomized to the intervention (daily use of lipid-rich emollient) or the control (no emollient) group (n = 625 infants in each) and are followed for 24 months. The primary outcome is the cumulative incidence of physician-diagnosed AD and secondary outcomes include caregiver-reported measures of AD and development of other atopic diseases. Data collection occurs via chart review and surveys, with no study visits required. Data will be analyzed utilizing intention-to-treat principles. DISCUSSION: AD is a common skin condition in infants that affects quality of life and is associated with the development of other atopic diseases. If a safe intervention, such as application of lipid-rich emollients, in the general population effectively decreases AD prevalence, this could alter the guidance given by providers regarding routine skin care of infants. Because of the pragmatic design, we anticipate that this trial will yield generalizable results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03409367. Registered on 11 February 2018.
Assuntos
Dermatite Atópica/prevenção & controle , Emolientes/administração & dosagem , Prevenção Primária/métodos , Higiene da Pele/métodos , Administração Cutânea , Análise Custo-Benefício , Dermatite Atópica/diagnóstico , Dermatite Atópica/economia , Emolientes/economia , Humanos , Incidência , Lactente , Estudos Multicêntricos como Assunto , Ensaios Clínicos Pragmáticos como Assunto , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Estados UnidosRESUMO
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.
Assuntos
Necessidades e Demandas de Serviços de Saúde/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Síndrome de Stevens-Johnson/terapia , Congressos como Assunto , Carga Global da Doença , Saúde Global , Humanos , Cooperação Internacional , Farmacogenética/organização & administração , Sistema de Registros/estatística & dados numéricos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Pesquisa Translacional Biomédica/organização & administraçãoRESUMO
BACKGROUND: Little is known about the burden of atopic dermatitis (AD) encountered in US primary care practices and the frequency and type of skin care practices routinely used in children. OBJECTIVE: To estimate the prevalence of AD in children 0 to 5 years attending primary care practices in the United States and to describe routine skin care practices used in this population. DESIGN: A cross-sectional survey study of a convenience sample of children under the age of 5 attending primary care practices for any reason. SETTING: Ten primary care practices in 5 US states. RESULTS: Among 652 children attending primary care practices, the estimated prevalence of ever having AD was 24% (95% CI, 21-28) ranging from 15% among those under the age of 1 to 38% among those aged 4 to 5 years. The prevalence of comorbid asthma was higher among AD participants compared to those with no AD, namely, 12% and 4%, respectively (P < .001). Moisturizers with high water:oil ratios were most commonly used (ie, lotions) in the non-AD population, whereas moisturizers with low water:oil content (ie, ointments) were most common when AD was present. CONCLUSIONS: Our study found a large burden of AD in the primary care practice setting in the US. The majority of households reported skin care practices that may be detrimental to the skin barrier, such as frequent bathing and the routine use of moisturizers with high water: oil ratios. Clinical trials are needed to identify which skin care practices are optimal for reducing the significant burden of AD in the community.
Assuntos
Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Atenção Primária à Saúde/estatística & dados numéricos , Higiene da Pele/métodos , Banhos/efeitos adversos , Banhos/estatística & dados numéricos , Estudos de Casos e Controles , Pré-Escolar , Comorbidade , Efeitos Psicossociais da Doença , Estudos Transversais , Estudos de Viabilidade , Humanos , Lactente , Pais , Prevalência , Índice de Gravidade de Doença , Higiene da Pele/efeitos adversos , Higiene da Pele/estatística & dados numéricos , Creme para a Pele/administração & dosagemRESUMO
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is one of the most devastating of adverse drug reactions (ADRs) and was, until recently, essentially unpredictable. With the discovery of several risk alleles for drug-induced SJS/TEN and the demonstration of effectiveness of screening in reducing incidence, the stage is set for implementation of preventive strategies in populations at risk. Yet much remains to be learned about this potentially fatal complication of commonly used drugs.
Assuntos
Predisposição Genética para Doença/genética , Testes Genéticos , Síndrome de Stevens-Johnson/genética , Predisposição Genética para Doença/prevenção & controle , Humanos , Incidência , Necrose , Valor Preditivo dos Testes , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/prevenção & controleRESUMO
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research. As a product of this meeting, this article summarizes the current state of knowledge and expert opinion related to SJS/TEN covering a broad spectrum of topics including epidemiology and pharmacogenomic networks; clinical management and complications; special populations such as pediatrics, the elderly, and pregnant women; regulatory issues and the electronic health record; new agents that cause SJS/TEN; pharmacogenomics and immunopathogenesis; and the patient perspective. Goals include the maintenance of a durable and productive multidisciplinary network that will significantly further scientific progress and translation into prevention, early diagnosis, and management of SJS/TEN.
Assuntos
Prova Pericial , Síndrome de Stevens-Johnson/epidemiologia , Idoso , Criança , Congressos como Assunto , Diagnóstico Precoce , Registros Eletrônicos de Saúde , Feminino , Humanos , Comunicação Interdisciplinar , Masculino , Gravidez , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/imunologia , Pesquisa Translacional Biomédica , Estados Unidos/epidemiologiaRESUMO
A coordinated effort combining bioinformatic tools with high-throughput cell-based screening assays was implemented to identify novel factors involved in T-cell biology. We generated a unique library of cDNAs encoding predicted secreted and transmembrane domain-containing proteins generated by analyzing the Human Genome Sciences cDNA database with a combination of two algorithms that predict signal peptides. Supernatants from mammalian cells transiently transfected with this library were incubated with primary T cells and T-cell lines in several high-throughput assays. Here we describe the discovery of a T cell factor, TIP (T cell immunomodulatory protein), which does not show any homology to proteins with known function. Treatment of primary human and murine T cells with TIP in vitro resulted in the secretion of IFN-gamma, TNF-alpha, and IL-10, whereas in vivo TIP had a protective effect in a mouse acute graft-versus-host disease (GVHD) model. Therefore, combining functional genomics with high-throughput cell-based screening is a valuable and efficient approach to identifying immunomodulatory activities for novel proteins.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Análise de Sequência de Proteína/métodos , Fatores Supressores Imunológicos/administração & dosagem , Fatores Supressores Imunológicos/química , Linfócitos T/metabolismo , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/genética , Adjuvantes Imunológicos/metabolismo , Animais , Linhagem Celular , Perfilação da Expressão Gênica/métodos , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Rim/química , Rim/embriologia , Rim/imunologia , Camundongos/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Fatores Supressores Imunológicos/genética , Fatores Supressores Imunológicos/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/genética , Linfócitos T/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Transfecção/métodosRESUMO
Multiple lines of evidence suggest that inhibition of Type I Interferons, including IFN-alpha, may provide a therapeutic benefit for autoimmune diseases. Using a chemical genomics approach integrated with cellular and in vivo assays, we screened a small compound library to identify modulators of IFN-alpha biological effects. A genomic fingerprint was developed from both ex vivo patient genomic information and in vitro gene modulation from IFN-alpha cell-based stimulation. A high throughput genomic-based screen then was applied to prioritize 268 small molecule inhibitors targeting 41 different intracellular signaling pathways. Active compounds were profiled further for their ability to inhibit the activation and differentiation of human monocytes using disease-related stimuli. Inhibitors targeting NF-kappaB or Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling emerged as "dissociated inhibitors" because they did not modulate IFN-alpha anti-viral effects against HSV-1 but potently inhibited other immune-related functions. This work describes a novel strategy to identify small molecule inhibitors for the treatment of autoimmune disorders.