Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease­2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.

Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis

Abstract: Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

Atopic dermatitis in adults: clinical and epidemiological considerations / Dermatite atópica em adultos: considerações clínicas e epidemiológicas

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory disease causing intense pruritus, and with typical clinical features. There are few epidemiological studies concerning AD in adults, as well as little information about its prognostic. The aim of this study was to evaluate the clinical and epidemiological course of adults with AD. METHODS: 80 patients aged above 18 years (mean age = 29 years) were selected (30 males and 50 females) and interviewed about hospitalization, systemic corticoid usage, age of AD onset, and personal and/or familial history of atopy. Disease severity was evaluated through the Scoring Atopic Dermatitis (SCORAD) tool. Laboratory examination included IgE serum levels and eosinophil blood count. RESULTS: 71 out of 80 patients referred association with respiratory symptoms (18 had asthma, 17 had rhinitis, and 36 had both conditions); nine out of 80 patients denied any respiratory disease. AD patients were divided in mild (n = 25), moderate (n = 30), and severe (n = 25); 56% had one or more hospitalizations due to AD. A positive association was found between IgE serum levels, eosinophil blood count, and disease severity. CONCLUSION: Adult AD represents a clinical challenge that needs to be better characterized, since it can be misdiagnosed and interferes with the patient's social and personal life. The association of skin and respiratory atopic disease is frequent, and laboratory parameters such as circulating IgE levels and eosinophil blood count may be helpful to assess disease severity.

OBJETIVO: Dermatite atópica (DA) é uma doenc¸a inflamatória crônica com prurido intenso e características clínicas típicas. Há poucos estudos epidemiológicos a respeito da DA em adultos, bem como pouca informação disponível sobre o seu prognóstico. O objetivo do presente estudo é avaliar as características clínicas e o curso epidemiológico dos adultos com DA. MÉTODOS: Foramselecionados 80 pacientes com idade acima de 18 anos (média de idade = 29 anos, 30 homens e 50 mulheres), que foram entrevistados sobre: internações, uso de corticóide sistêmico, idade de início da DA, história pessoal e/ou familiar de atopia. A gravidade da doença foi avaliada de acordo com o SCORing Atopic Dermatitis (SCORAD). A avaliação laboratorial incluiu dosagem sérica de IgE e contagem sanguínea de eosinófilos. RESULTADOS: 71 dos 80 pacientes referiram associação com sintomas respiratórios (18: asma, 17: rinite alérgica e 36: ambas as condições); nove dos 80 indivíduos negaram qualquer sintoma respiratório. Os pacientes com DA foram divididos em DA leve (n = 25), moderada (n = 30) e grave (n = 25); destes, 56% tiveram uma ou mais internações por conta da doença. Verificou-se uma associação entre níveis séricos de IgE, contagem sanguínea de eosinófilos e gravidade da doença. CONCLUSÃO: A DA do adulto representa um desafio clínico que necessita ser melhor caracterizado, uma vez que pode ser erroneamente diagnosticada, e interfere diretamente na vida social e pessoal dos pacientes. A associação entre manifestação respiratória e cutânea é frequente, e parâmetros laboratoriais como níveis de IgE circulante e contagem sanguínea de eosinófilos podem ser úteis para acompanhar a gravidade e evolução da doença.

Study on lymphocyte proliferation in nickel sensitive patients / Estudo da proliferação linfocitária em pacientes sensibilizados ao niquel

Fundamento: O diagnóstico da alergia ao níquel é estabelecido com a realização do teste de contato. Objetivo: Desenvolver um método diagnóstico mais sensível e específico.Casuísticas e Métodos: Dezenove pacientes com teste de contato positivo para o níquel e 25 controles foram submetidos ao teste da proliferação linfocitária. As células mononucleadas foram isoladas do sangue venoso periférico e cultivadas em triplicatas, em placas de cultura (2×105 células/orifício) com: meio de cultura apenas; sulfato de níquel (156,25; 78,13; 19,53; 9,77 e 2,44µM) e concentrações ideais do antígeno Candida albicans e dos mitógenos pokeweed, fito-hemaglutinina A e anticorpo anti-CD3 (OKT3). Timidina tritiada foi adicionada às placas, a radioatividade incorporada pelas células medida e os resultados expressos pelo índice de estimulação (IE).Resultados: A resposta proliferativa dos linfócitos dos casos foi superior à dos controles em todas as concentrações de níquel testadas. Considerando teste positivo para níquel quando IE ≥ 3, nenhum dos controles e 16 (84,21por cento) dos casos apresentaram teste positivo em pelo menos uma das cinco concentrações usadas. As respostas à Candida albicans e aos mitógenos foram semelhantes nos casos e controles, demonstrando a integridade da imunidade celular em ambos os grupos.Conclusão: O teste da proliferação linfocitária mostra-se útil no diagnóstico da alergia ao níquel

Inibicao da resposta de hipersensibilidade do tipo I da prole de camundongos mediada pela imunizacao materna com o acaro Dermatophagoides pteronyssinus / Inhibition of offspring type I hypersensitivity response through maternal immunization with the dust mite Dermatophagoides pteronyssinus

A exposicao precoce a alergenos associada a tendencia dos neonatos a desenvolverem respostas do tipo Th2 pode...

Induçäo a tolerancia a aloantigenos por via oral em camundongos submetidos a alotransplante de pele / Tolerance indution to alloantigens by oral administration in submited mice to the skin allotransplantation

Na Imunologia dos Transplantes, um dos aspectos fundamentais e a tentativa de imunomodulaçäo do aloenxerto, sem a induçäo de efeitos deletereos secundários, como os observados em métodos clássicos de imunossupressao. As terapias imunossupressoras constituem uma pratica comum nos centros de transplantes, promovendo a inibiçäo preventiva da resposta imunologica. Os agentes supressores atualmente empregados apresentam uma eficacia consideravel em aumentar a sobrevida do enxerto. Entretanto, sua utilizaçäo prolongada e sua inespecificidade de açäo podem aumentar a suscetibilidade a infecçöes e ao desenvolvimento de neoplasias no hospedeiro. A tolerância oral, induzida com aloantigenos (celulas imunocompetentes), tem demonstrado ser uma terapia de imunomodulaçäo ao da resposta a aloantigenos...