Is allergen immunotherapy a model of personalized treatment in pediatric respiratory allergy?

PURPOSE OF REVIEW: To review recent evidence on allergen immunotherapy (AIT) as a model of personalized medicine in the treatment of children and adolescents with respiratory allergies. RECENT FINDINGS: Meta-analysis and systematic review studies continue to point out that AIT is an effective treatment for children with respiratory allergies. Molecular allergy allows the understanding of patient sensitization profiles that frequently change the prescription of AIT. There is still a lack of evidence showing that this personalized prescription of AIT is associated with better clinical outcomes. The nasal allergen challenge has extended the indications of AIT for a new group of subjects with local allergic rhinitis. Patient selection of allergens involved in the increasingly personalized composition of extracts to be used in AIT increasingly characterizes it as personalized medicine. SUMMARY: Despite the numerous studies carried out to identify the best biomarker to evaluate the response to AIT, there is still much disagreement, and clinical assessment (symptoms, quality of life, among others) continues to be the best way to evaluate the therapeutic success of AIT.

Good clinical practice recommendations in allergen immunotherapy: Position paper of the Brazilian Association of Allergy and Immunology - ASBAI.

Background: Allergen Immunotherapy (AIT) represents one of the pillars in the treatment of allergic diseases. AIT is the only therapeutic strategy with curative potential, promoting the reduction of drug use and long-term symptom control even after the end of the treatment. The European Academy of Allergy, Asthma and Immunology (EAACI) guidelines, position papers of World Allergy Organization (WAO), and the US Practice Parameters are the leading official documents that set scientific standard for the use of AIT in the world. The use of AIT in Brazil has specific regional conditions due to the pattern of allergen sensitization, as well as genetic, socioeconomic, and cultural characteristics, climate conditions, and the availability of allergenic extracts. The most prevalent house dust mites are Dermatophagoides pteronyssinus, Dermatophagoides farinae and their allergens have the highest clinical relevance. Blomia tropicalis is also very frequent. This position paper has been prepared by the Brazilian Association of Allergy and Clinical Immunology (ASBAI) Taskforce on AIT for respiratory allergy and Hymenoptera venom allergy. Objective: According to the current scientific literature adapted to the Brazilian reality, this position paper aims to establish the main recommendations for the good clinical practice parameters for AIT in Brazil. Methods: A systematic review using the Pub Med and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. The research was limited to English language literature and was conducted between March 30, 2002, and March 30, 2022. The terms used for the research were: Allergen Immunotherapy, sublingual immunotherapy (SLIT), subcutaneous immunotherapy (SCIT), venom-specific immunotherapy (VIT), and allergen extract. Results: The several recommendations that establish the clinical practices for AIT recommended by the main Allergy, Asthma and Immunology world organizations were analyzed and adapted to the Brazilian situation. Conclusion: This position paper establishes the main recommendations for the effective clinical practice of AIT in Brazil, using current knowledge of evidence-based medicine and precision medicine.

Coronavirus Disease 2019 Vaccination for Cancer Patients: Risk or Benefit?

OBJECTIVE: The aim of the present study is to list the published clinical trials on coronavirus disease 2019 (COVID-19) vaccines, to describe the mechanism of action of the identified vaccines, and to identify protocols regarding safety, status, and prioritization of cancer patients for vaccination. METHODS: This is a systematic review with a limited literature search conducted by an information specialist; key resources such as PubMed and websites of major cancer organizations were searched. The main search terms were COVID-19, vaccination, cancer, and breast and gynecological cancers. RESULTS: Cancer patients infected with the new coronavirus are at high risk of complications and death, but we still know little about the risks and benefits of vaccination for COVID-19 in these patients. In an ideal scenario, all cancer patients should have their immunization status updated before beginning treatment, but this is not always possible. CONCLUSION: Patients with breast or gynecological cancers who are receiving treatment or are in the 5-year posttreatment period should be included in the priority group for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination.

OBJETIVO: O objetivo do presente estudo é listar os ensaios clínicos publicados sobre as vacinas para coronavirus disease 2019 (COVID-19), descrever seus mecanismos de ação e descrever protocolos sobre segurança, status e priorização de pacientes oncológicos para vacinação. MéTODOS: Trata-se de uma revisão sistemática com uma pesquisa bibliográfica limitada conduzida por um especialista em informação; bases de dados como PubMed e sites das principais organizações de câncer foram pesquisados. Os principais termos de pesquisa foram COVID-19, vacinação, câncer e câncer de mama e ginecológico. RESULTADOS: Pacientes com câncer infectados com o novo coronavírus têm alto risco de complicações e morte, mas ainda sabemos pouco sobre os riscos e benefícios da vacinação para COVID-19 nesses pacientes. Em um cenário ideal, todos os pacientes com câncer deveriam ter seu estado de imunização atualizado antes de iniciar o tratamento, mas nem sempre isso é possível. CONCLUSãO: Pacientes com câncer de mama ou ginecológico em tratamento ou no período pós-tratamento de 5 anos devem ser incluídos no grupo prioritário para vacinação contra severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2.).

Coronavirus Disease 2019 Vaccination for Cancer Patients: Risk or Benefit? / Vacinação para COVID-19 em pacientes oncológicos: Risco ou benefício?

Abstract Objective The aim of the present study is to list the published clinical trials on coronavirus disease 2019 (COVID-19) vaccines, to describe the mechanism of action of the identified vaccines, and to identify protocols regarding safety, status, and prioritization of cancer patients for vaccination. Methods This is a systematic review with a limited literature search conducted by an information specialist; key resources such as PubMed and websites of major cancer organizations were searched. The main search terms were COVID-19, vaccination, cancer, and breast and gynecological cancers. Results Cancer patients infected with the new coronavirus are at high risk of complications and death, but we still know little about the risks and benefits of vaccination for COVID-19 in these patients. In an ideal scenario, all cancer patients should have their immunization status updated before beginning treatment, but this is not always possible. Conclusion Patients with breast or gynecological cancers who are receiving treatment or are in the 5-year posttreatment period should be included in the priority group for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination.

Resumo Objetivo O objetivo do presente estudo é listar os ensaios clínicos publicados sobre as vacinas para coronavirus disease 2019 (COVID-19), descrever seus mecanismos de ação e descrever protocolos sobre segurança, status e priorização de pacientes oncológicos para vacinação. Métodos Trata-se de uma revisão sistemática com uma pesquisa bibliográfica limitada conduzida por um especialista em informação; bases de dados como PubMed e sites das principais organizações de câncer foram pesquisados. Os principais termos de pesquisa foram COVID-19, vacinação, câncer e câncer de mama e ginecológico. Resultados Pacientes com câncer infectados com o novo coronavírus têm alto risco de complicações e morte, mas ainda sabemos pouco sobre os riscos e benefícios da vacinação para COVID-19 nesses pacientes. Em um cenário ideal, todos os pacientes com câncer deveriam ter seu estado de imunização atualizado antes de iniciar o tratamento, mas nem sempre isso é possível. Conclusão Pacientes com câncer de mama ou ginecológico em tratamento ou no período pós-tratamento de 5 anos devem ser incluídos no grupo prioritário para vacinação contra severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2.)

Avaliação da expressão da filagrina em biópsias esofágicas de pacientes com esofagite eosinofílica / Evaluation of philagrin expression in esophageal biopsies of patients with eosinophilic esophagitis

Introdução: Mutações do gene da filagrina vêm sendo associadas, classicamente, a alterações da barreira epitelial em doenças alérgicas com comprometimento da pele e das superfícies mucosas. Particularmente na dermatite atópica, a relação entre filagrina, mecanismo fisiopatológico e evolução clínica tem sido demonstrada. Recentemente, alterações da barreira epitelial com redução da expressão da filagrina, também têm sido associadas a mecanismos imunológicos envolvidos na patogênese da esofagite eosinofílica. Devido a disfunções na barreira epitelial, microrganismos e alérgenos são capazes de penetrarem no epitélio da mucosa esofágica, assim como na dermatite atópica. Objetivo: Avaliar a possível correlação da expressão da filagrina com os achados histopatológicos em biópsias esofágicas de pacientes com esofagite eosinofílica. Métodos: A expressão da filagrina foi investigada in situ, por imuno-histoquímica, em biópsias esofágicas nos seguintes grupos: Grupo I, controle (n=8), amostras provenientes de pacientes saudáveis; Grupo II (n=27), amostras provenientes de pacientes com esofagite eosinofílica. Resultados: Os resultados demonstraram uma diminuição da expressão da filagrina na mucosa do esôfago de portadores de esofagite eosinofílica. Adicionalmente, a intensidade da marcação imuno-histoquímica foi menor na mucosa esofágica com maior infiltração de eosinófilos. Conclusão: A diminuição da expressão de filagrina pode ser um fenomeno fisiopatológico associado ao aumento da quantidade de eosinófilos na mucosa esofágica, podendo impactar na evolução clínica da esofagite eosinofílica.

Introduction:Filaggrin gene mutations have been classically associated with changes in the epithelial barrier in allergic diseases involving the skin and mucosal surfaces. Particularly in atopic dermatitis, the relationship between filaggrin, pathophysiological mechanism and clinical evolution hás been demonstrated. Recently, changes in the epithelial barrier with reduced expression of filaggrin have also been associated with immunological mechanisms involved in the pathogenesis of eosinophilic esophagitis. Due to dysfunction in the epithelial barrier, microorganisms and allergens are able to penetrate the epithelium of the esophageal mucosa, as well as in atopic dermatitis. Objective: To evaluated the possible correlation of filaggrin expression with histopathological findings in esophageal biopsies of patients with eosinophilic esophagitis. Methods: Filaggrin expression was investigated in situ by immunohistochemistry in esophageal biopsies in the following groups: Group I, control (n = 8), samples from healthy patients; Group II (n = 27), samples from patients with eosinophilic esophagitis. Results: The results demonstrated a decrease in the expression of filaggrin in the esophageal mucosa of patients with eosinophilic esophagitis. Additionally, the intensity of the immunohistochemical labeling was lower in the esophageal mucosa with greater infiltration of eosinophils. Conclusion: The reduction of filaggrin expression may be a pathophysiological phenomenon associated with an increase in the quantity of eosinophils in the esophageal mucosa, which may impact on the clinical evolution of eosinophilic esophagitis.

Bone Neoformation Induced by Low-Level Laser and Methylene Blue Suggests Early Ossification in Rats.

Introduction: Bone healing depends on inflammation control and tissue repair time. Low-level laser therapy (LLLT) has been investigated to accelerate this process. Methylene blue (MB), together with LLLT, has been investigated for its antioxidant and anti-inflammatory potential; however, the effects of photosensitizers (photodynamic therapy, PDT) are controversial. This study aimed to verify whether the combination of MB and LLLT changes the course of the consolidation of experimental bone defects. Methods: Sixteen Wistar rats underwent femoral bone defects. In the control group (n=4), LLLT simulations were performed without MB. The MB group (n=4) received MB and simulation of LLLT. The LLLT group (n=4) was exposed to LLLT. The PDT+LLLT group (n=4) received MB and LLLT. At the end of 7 or 14 days, the animals were euthanized, and samples were collected. Results: PDT and LLLT induced osteogenic formation with cellularity (after seven days) and union of bony edges (14 days). On the seventh day, LLLT combined with PDT induced an increase (P<0.05) of 484% in the area of bone neoformation compared to the control. On the fourteenth day, LLLT combined with PDT or alone increased (P<0.05) the area of bone neoformation by 214% and 240% respectively, compared to the control group. The PDT/LLLT combination was associated with increased radiopacity (P<0.038). Conclusion: The combined use of MB with LLLT initiated during the transoperative phase may stimulate the bone repair process in rats.

Avaliação do emprego da imunoglobulina humana endovenosa sobre a densidade de infecções em pacientes com mieloma múltiplo / Evaluation of the use of human intravenous immunoglobulin on the incidence density of infections in patients with multiple myeloma

Introdução: O mieloma múltiplo (MM) é uma neoplasia hematológica que cursa com hipogamaglobulinemia e consequente imunodeficiência secundária. Uma das principais causas de morbimortalidade desses pacientes são infecções. Objetivou-se com esse estudo avaliar o impacto da reposição de imunoglobulina endovenosa (IgIV) na taxa de infecções em pacientes portadores de MM. Métodos: Trata-se de um estudo de análise documental, com variáveis qualitativas e quantitativas, com objetivo de realizar análise retrospectiva dos prontuários de pacientes com MM que receberam tratamento com imunoglobulina humana endovenosa em um hospital privado na cidade de Patos de Minas, MG, Brasil, no período de 01/05/2016 a 31/12/2020. Foram coletados dados epidemiológicos, resultados de exames, episódios de infecções, eventos adversos da medicação e desfecho dos pacientes nos prontuários analisados. Resultados: Foram identificados 10 pacientes com diagnóstico de MM, todos receberam IgIV na dose de 300 a 400 mg/kg/mês. Nenhuma reação adversa relacionada ao uso da IgIV foi registrada nos prontuários. Foram identificados seis quadros infecciosos que ocorreram em quatro pacientes. Nenhum diagnóstico de sepse foi registrado. A densidade de incidência de infecções foi de 0,28 episódios/pacientes-ano. Conclusão: A densidade de incidência de infecções observada no presente estudo foi significativamente menor em comparação ao que se tem registro na literatura, sugerindo importante papel da IgIV na prevenção de infecções em pacientes com MM.

Introduction: Multiple myeloma (MM) is a hematologic malignancy that leads to hypogammaglobulinemia and consequent secondary immunodeficiency. Infections are a major cause of morbidity and mortality in these patients. The objective of this study was to evaluate the impact of intravenous immunoglobulin (IVIg) replacement on the rate of infections in patients with MM. Methods: This document analysis study used qualitative and quantitative variables to perform a retrospective analysis of the medical records of patients with MM who were treated with human IVIg in a private hospital in the city of Patos de Minas, MG, Brazil, from May 1, 2016 to December 31, 2020. Epidemiological data, test results, episodes of infections, adverse medication events, and patient outcomes were collected from the medical records. Results: Ten patients diagnosed with MM were identified, and they all received IVIg at a dose of 300 to 400 mg/kg/month. No adverse reactions related to the use of IVIg were recorded. Six infections that occurred in 4 patients were identified. No diagnosis of sepsis was recorded. The incidence density of infections was 0.28 episodes/patient-years. Conclusion: The incidence density of infections was significantly smaller in this study in comparison with previous literature findings, which suggests a significant role of IVIg in the prevention of infections in patients with MM.

Satisfaction of allergic patients treated with house dust mite sublingual immunotherapy.

Sublingual immunotherapy (SLIT) has been used for more than three decades as a therapeutic strategy for the treatment of allergic diseases. Studies have demonstrated its efficacy and safety, and numerous clinical trials have evaluated these parameters. In the present study, through patient perception, we investigated the patient satisfaction with the use of house dust mite SLIT treatment. "Satisfaction Scale for Patients Receiving Allergen Immunotherapy" (ESPIA) questionnaire, a standardized and validated instrument for clinical studies evaluating allergen immunotherapy, was applied to allergic patients (N = 136). Children and adults of both sexes who received SLIT for Dermatophagoides pteronyssinus and/or Blomia tropicalis, according to the results of an immediate reading puncture test, were included. Data analysis showed that the perception of treatment effectiveness was 92%, performance improvement in the daily activities was 91%, a satisfactory cost-benefit balance was 84%, and the perception of general satisfaction was 97%. The results showed a high perception of satisfaction in allergic patients undergoing house dust mite SLIT.

Induced oral mucositis in Wistar rats treated with different drugs: Preventive potential in cytokine production.

The aim of the present study was to investigate the preventive potential of pentoxifylline, atorvastatin and trans-caryophyllene in oral mucositis through histopathological analysis of wounds in the oral mucosa of Wistar rats treated with 5-FU, and to evaluate the immunomodulatory effect of these drugs on serum nitrite production, in situ IFN-γ, TNF-α and TGF-ß, and TNF-α in tissues. A total of 32 male Wistar rats with an average age of 9 weeks and an average body weight of 250 g were divided into four treatment groups: Saline, trans-caryophyllene, pentoxifylline and atorvastatin. Oral mucositis was then induced. On days 3 and 4, the mucosa of the mouth of eight pre-treated animals in each group was bilaterally scarified twice with the tip of a sterile needle, with an anesthetic solution. Mucosal samples from animals treated with trans-caryophyllene preserved a thin epithelial lining associated with focal perivascular inflammatory infiltrates. Pentoxifylline-treated animals exhibited total epithelial loss in oral wounds with severe inflammatory infiltrates and mild re-epithelialization associated with mild and diffuse inflammatory infiltrates. Samples from atorvastatin-treated animals exhibited no epithelial dissolution, with preserved thin lining and mild diffuse inflammatory infiltrates. The analysis of TNF-α expression revealed improved results in trans-caryophyllene animals. The analysis of TGF-ß expression revealed positive mononuclear cells. Preventive treatment with atorvastatin was demonstrated to modulate the serum expression levels of TNF-α during all stages of the experiment. Treatment with trans-caryophyllene modulated serum IFN-γ levels negatively, whereas treatment with atorvastatin and trans-caryophyllene maintained lower levels of IFN-γ compared with the control group.

Posicionamento da Associação Brasileira de Alergia e Imunologia sobre o manejo da imunoterapia específica com alérgenos (ITA) em pacientes vacinados contra COVID­19 / Position statement of the Brazilian Association of Allergy and Immunology on the management of allergen-specific immunotherapy (AIT) in patients vaccinated against COVID­19

A pandemia de COVID-19 representa um grande desafio para todas as especialidades médicas. A imunoterapia com alérgenos (ITA) é considerada o único procedimento terapêutico capaz de modificar a história natural das doenças alérgicas, e caracteriza o estado da arte na área de Alergia e Imunologia. Esta estratégia terapêutica de imunomodulação é capaz de promover a remissão e controle das doenças alérgicas por períodos prolongados, mesmo após o seu término. Existem poucos dados em relação ao emprego da ITA em pacientes vacinados contra COVID-19, e até o momento não há um posicionamento oficial das sociedades internacionais da área de Alergia e Imunologia Clínica. Este documento tem como objetivo estabelecer recomendações práticas para o manejo da ITA em pacientes que receberam a vacina contra COVID-19. Os fenômenos imunológicos envolvidos na imunoprofilaxia vacinal e no mecanismo de ação da ITA foram comparados, proporcionando o estabelecimento de recomendações precisas.

The COVID-19 pandemic represents a serious challenge for all medical specialties. Allergen-specific immunotherapy (AIT) is considered the only therapeutic procedure capable of modifying the natural history of allergic diseases and characterizes the state of the art in the field of allergy and immunology. This therapeutic strategy of immunomodulation is able to promote remission and control of allergic diseases for prolonged periods, even after cessation. There are few data regarding use of AIT in patients vaccinated against COVID-19 and, to date, there is no official position statement published by international allergy and clinical immunology societies. This document aims to establish practical recommendations for the management of AIT in patients who have received the COVID-19 vaccine. The immunological mechanisms involved in immunoprophylaxis with vaccines and the mechanism of action of AIT have been compared to provide a solid basis for establishing precise recommendations.

New model of Oral Mucositis with 5-Fluorouracil chemo-induced in Wistar rats without the use of anesthesics / Novo modelo de Mucosite Oral quimioinduzida com 5-Fluorouracil em ratos Wistar sem uso de anestésicos

ABSTRACT Introduction: Oral mucositis (OM) is considered the most frequent acute side effect of the antineoplasic treatment, with ulcerative lesions resulting from a painful symptomatology, affecting the oral cavity in response to the Antineoplastic treatment. In order to study these side effects, experiments in animal models are necessary, using antineoplastic drugs for the induction of OM and anesthetics, mainly Ketamine and Xylazine, to perform scarification of the cheeks. Objective: The goal is to report an experimental model of induced OM, without the use of anesthetics for the scarification stage of the animal cheeks. Methods: Fourty five male Wistar rats, 7 weeks old and weighting 220g, were used, divided into 2 groups; with OM induced by 5-Fluorouracil intraperitoneal administration. Two days later, Group I was physically contained, in contrast, Group II were anesthetized with Ketamine and Xylazine, focusing on irritating the cheek mucosa using the tip of a sterile needle, in order to potentialize the development of OM. The animals were euthanized with an anesthetic overdose. Results: Concerning the experiment of 5-Fluorouracil chemo-induced of OM, where the irritation was performed by physical containment, without the use of anesthetics (Ketamine and Xylazine), the animals had a longer survivability and a rapid improvement of the side effects induced by chemotherapy. Conclusion: This new model is promising, considering that the use of anesthetics (Ketamine and Xylazine) showed a high mortality rate. In the absence of anesthesia, all the animals survived until the end of the experiment involving chemotherapy model with 5-Fluorouracil and physical restraint.

RESUMO Introdução: A mucosite oral (MO) é considerada o efeito colateral agudo mais frequente do tratamento antineoplásico, com lesões ulcerativas decorrentes de sintomatologia dolorosa, acometendo a cavidade oral em resposta ao tratamento antineoplásico. Para estudar esses efeitos colaterais, são necessários experimentos em modelos animais, utilizando fármacos antineoplásicas para a indução de MO e anestésicos, principalmente Cetamina e Xilazina, para realizar a escarificação das bochechas Objetivos: Relatar um novo modelo experimental de MO induzida, sem o uso de anestésicos, para a etapa de escarificação das bochechas dos animais. Métodos: Foram utilizados 45 ratos Wistar machos, com 7 semanas de idade e peso de 220g, divididos em 2 grupos com MO induzida pela administração intraperitoneal de 5-fluorouracil. Dois dias depois, o Grupo I foi contido fisicamente, ao contrário, o Grupo II foi anestesiado com Cetamina e Xilazina, com foco em irritar a mucosa da bochecha com a ponta de uma agulha estéril, a fim de potencializar o desenvolvimento de MO. Os animais foram eutanasiados com sobredose de anestésica. Resultados: Em relação ao experimento de 5-Fluorouracil quimioinduzido para MO, onde a irritação foi realizada por contenção física, sem o uso de anestésicos (Cetamina e Xilazina), os animais tiveram maior sobrevida e rápida melhora dos efeitos colaterais induzidos por quimioterapia. Conclusão: Este novo modelo é promissor, visto que o uso de anestésicos (Cetamina e Xilazina) apresentou elevada mortalidade. Porém, na ausência de anestesia, todos os animais sobreviveram até o final do experimento envolvendo este modelo de quimioterapia induzida com 5-fluorouracil e contenção física.

Intranasal drug delivery devices are a potential contamination source of airways / Dispositivos intranasais de medicamentos são uma potencial fonte de contaminação das vias aéreas

Background: The use of intranasal drug delivery devices (IDDD) for the treatment of allergic rhinitis (AR) is frequent because they are simple, efficient, and safe, and mainly because they are perceived as low-risk. However, it is speculated that contact between the nasal mucosa and an IDDD may give rise to infections once the nose is colonized by bacteria, and there are currently no proper instructions for IDDD sanitization. The objective of this study was to evaluate the possibility of contamination of an IDDD for topical medication after simulating use in healthy individuals. Methods: The in vitro study consisted of 14 healthy individuals of both sexes, between the ages of 18 and 24 years. Samples were collected immediately after the opening of each IDDD and after simulating use by the subjects. Afterwards, the samples were deposited in tubes and kept in an incubator at 37 °C. After 48 hours, the samples were inoculated on Müller-Hinton agar. Qualitative analyses of the appearance of the samples were performed after 24 and 48 hours, and after 72 hours the presence or absence of bacteria was evaluated macroscopically. Results: After 24 hours of incubation, 21.4% (n = 3) of the samples presented with a turbid appearance and after 48h, 71% (n = 10) of the samples presented with a turbid appearance and positive bacterial growth. Conclusion: The results suggest that IDDDs for topical medications may be important sources of contamination or recontamination of the nasal mucosa of individuals who are being treated for upper respiratory tract conditions. A better understanding of the risks of re-using IDDDs after previous contact with the nasal mucosa will improve guidelines on hygiene procedures and prevention of related risks.

Introdução: O uso de dispositivos intranasais para administração de medicamentos (IDDD) no tratamento da rinite alérgica (AR) é frequente, por serem simples, eficientes e seguros, e principalmente por serem de baixo risco. No entanto, especula-se que o contato entre a mucosa nasal e um IDDD possa causar infecções, uma vez que o nariz é colonizado por bactérias, e atualmente não há instruções adequadas para a higienização do IDDD. O objetivo deste estudo foi avaliar a possibilidade de contaminação de um IDDD para medicação tópica após simulação de uso em indivíduos saudáveis. Métodos: O estudo in vitro foi composto por 14 indivíduos saudáveis, de ambos os sexos, com idades entre 18 e 24 anos. As amostras foram coletadas imediatamente após a abertura de cada IDDD, e após a simulação do uso pelos sujeitos. Posteriormente, as amostras foram depositadas em tubos e mantidas em incubadora a 37 °C. Após 48 horas, as amostras foram inoculadas em ágar Müller-Hinton. As análises qualitativas da aparência das amostras foram realizadas após 24 e 48 horas, e após 72 horas a presença ou ausência de bactérias foi avaliada macroscopicamente. Resultados: Após 24 horas de incubação, 21,4% (n = 3) das amostras apresentaram aparência turva e, após 48h, 71% (n = 10) das amostras apresentaram aparência turva e crescimento bacteriano positivo. Conclusão: Os resultados sugerem que IDDDs para medicações tópicas podem ser importantes fontes de contaminação ou recontaminação da mucosa nasal de indivíduos em tratamento para condições do trato respiratório superior. Uma melhor compreensão dos riscos da reutilização de IDDDs após contato prévio com a mucosa nasal, melhorará as diretrizes sobre procedimentos de higiene e prevenção de riscos relacionados.

Imunoterapia e imunobiológicos na dermatite atópica / Immunotherapy and immunobiologicals in atopic dermatitis

Na última década, avanços consideráveis na compreensão da patogênese da dermatite atópica têm pavimentado a via de um número de novos tratamentos. A melhora da imunoterapia subcutânea com alérgenos e a introdução da imunoterapia sublingual deram lugar à prospecção de sua aplicação para adultos e crianças portadoras de dermatite atópica. Esta revisão apresenta resultados das pesquisas científicas, análises sistemáticas e metanálises que confirmam a eficácia clínica da imunoterapia com alérgenos para pacientes com dermatite atópica de curso moderado ou grave, que apresentam sensibilização a aeroalérgenos. Apresentamos também novas informações de como usar os bioterapêuticos que estão levando a tentativas mais eficazes de tratamento. A esperança é de que estes novos biológicos ou antagonistas de pequenas moléculas, que têm alta especificidade para as moléculas-alvo, possam diminuir os efeitos indesejáveis causados pelos agentes imunossupressivos sem um alvo específico, como os observados pelas drogas de ampla ação biológica. Com o desenvolvimento e subsequentemente com a aprovação dos bioterapêuticos pelas agências reguladoras, nós começamos a ver uma revolução clínica e terapêutica no tratamento da dermatite atópica. As fontes de dados incluíram artigos originais, revisões e publicações indexados nos bancos de dados PubMed, MEDLINE, LILACS, SciELO e publicações on-line nos últimos 15 anos. Como resultado, uma nova era no tratamento de pacientes com doenças crônicas graves está em andamento na nossa especialidade. O uso de imunoterapia subcutânea, imunoterapia sublingual e bioterapêuticos para dermatite atópica prometem grande precisão e efetividade na medicina personalizada.

In the past decade, considerable advances in our understanding of the pathogenesis of atopic dermatitis have paved the way for a number of new treatments. The improvement of subcutaneous allergen immunotherapy and the introduction of sublingual immunotherapy provided prospects of their administration both for adults and children suffering from atopic dermatitis. This review includes results of scientific studies, systematic reviews and metaanalyses that confirm the clinical efficacy of allergen immunotherapy for patients with moderate and severe atopic dermatitis who are sensitive to aeroallergens. Also, new information on how the use of biotherapeutics is leading to more effective approaches to treatment is presented. Hopefully these new biologicals or small molecule antagonists, which have high specificity for their target molecules, will decrease the undesirable off-target effects commonly observed with current immunosuppressive agents that are characterized by broad biological actions. With the development and subsequent regulatory approval of biotherapeutic agents, a clinical and therapeutic revolution has begun in the treatment of atopic dermatitis. Data sources included original articles, reviews and related texts published over the past 15 years, retrieved from PubMed, MEDLINE, LILACS and SciELO databases and other online publications. As a result, a new era in the treatment of patients with severe chronic diseases has been observed in our specialty. The use of subcutaneous allergen immunotherapy, sublingual immunotherapy and biotherapeutics for atopic dermatitis promises greater precision and effectiveness in a personalized medicine.

COMPARISON BETWEEN THE ENDOSCOPIC FINDINGS AND THE HISTOLOGICAL DIAGNOSIS OF ANTRAL GASTRITES.

BACKGROUND: Gastritis is a very common disorder that is widely distributed worldwide, representing one of the most prevalent pathological entities in Gastroenterology and Digestive Endoscopy. OBJECTIVE: This study aims to analyze the correlation between the endoscopic findings and the histological diagnosis of antral gastritis. METHODS: In this study, 92 reports of upper digestive endoscopy were performed between November 2014 and January 2015, including biopsy of the antral gastric mucosa, comparing the endoscopic and histological findings, which were classified according to the Sidney System. The 92 exams included 35 men and 57 women, ranging in age from 15 to 84 years. The most frequent indication was epigastric pain. RESULTS: Of the 92 examinations analyzed, the histological diagnosis of antral gastritis appeared in 75 exams, 59 endoscopic reports contained the diagnosis of antral gastritis, and 33 endoscopic findings were normal. The kappa coefficient was 0.212 (P<0.05), indicating that there was no significant agreement between the endoscopic findings and the histological diagnosis of antral gastritis. CONCLUSION: We conclude that histology represents the gold standard method for the diagnosis of antral gastritis and that in daily clinical practice, biopsies should always be performed, regardless of the endoscopic findings.

Brazilian experience with atopy patch tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis.

BACKGROUND: The aim of this study was to evaluate the positivity rates of atopy patch tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis in patients with respiratory diseases such as asthma and allergic rhinitis with or without atopic dermatitis. METHODS: The patients' clinical histories were collected, and the patients were subjected to skin prick and patch tests with the three different house dust mites on the same day. The patch tests were examined 48 hours later, and then patients were divided into two groups: I- patients with respiratory diseases, such as asthma and/or rhinitis, and atopic dermatitis and II-patients with only respiratory diseases. A total of 74 patients ranging in age from 2 to 60 years were included in this study; 16 patients were included in group I and 58 were included in group II. This study was approved by the human ethics committee of the Faculty of Medical Science and Health SUPREMA (number 2.007.135), and written informed consent was collected from each patient or their parents prior to enrollment. RESULTS: In the skin prick tests, the most prevalent mite that evoked a reaction was Dermatophagoides pteronyssinus, followed by Dermatophagoides farinae and Blomia tropicalis. Regarding the atopy patch tests, the mite that most frequently induced a positive reaction was Dermatophagoides farinae (78.4%), followed by Dermatophagoides pteronyssinus (77%) and Blomia tropicalis (52.7%). A comparison of the skin prick and atopy patch tests revealed that 53 patients (71.6%) were positive on both tests, and 30 (56.6%) patients were positivite for the same mite. We found six patients (8%) who had a positive clinical history of allergy and only exhibited positivity on the atopy patch test. DISCUSSION: Most studies have been performed with atopic dermatitis patients, but in this study, most of the patients had respiratory conditions. Blomia tropicalis is a mite that is prevalent in tropical areas, such as Brazil, and only two publications include these three mites, wich are present in Brazil. The APT may produce positive results in concordance with the SPT resuts, but may also be the only positive test ( 8%) as we observed in our study. These results suggest that the mite atopy patch test is relevant and should be considered as an additional test for patients with clinical histories of allergic respiratory disease who have negative prick test results. CONCLUSION: The APT should be considered as an additional test when the SPT and specific serum IgE tests are negative in patients with clinical histories of allergies.

Comparação entre os achados endoscópicos e o diagnóstico histológico de gastrite antral. Arq Gastroenterol / Comparison between the endoscopic findings and the histological diagnosis of antral gastrites

ABSTRACT BACKGROUND: Gastritis is a very common disorder that is widely distributed worldwide, representing one of the most prevalent pathological entities in Gastroenterology and Digestive Endoscopy. OBJECTIVE: This study aims to analyze the correlation between the endoscopic findings and the histological diagnosis of antral gastritis. METHODS: In this study, 92 reports of upper digestive endoscopy were performed between November 2014 and January 2015, including biopsy of the antral gastric mucosa, comparing the endoscopic and histological findings, which were classified according to the Sidney System. The 92 exams included 35 men and 57 women, ranging in age from 15 to 84 years. The most frequent indication was epigastric pain. RESULTS: Of the 92 examinations analyzed, the histological diagnosis of antral gastritis appeared in 75 exams, 59 endoscopic reports contained the diagnosis of antral gastritis, and 33 endoscopic findings were normal. The kappa coefficient was 0.212 (P<0.05), indicating that there was no significant agreement between the endoscopic findings and the histological diagnosis of antral gastritis. CONCLUSION: We conclude that histology represents the gold standard method for the diagnosis of antral gastritis and that in daily clinical practice, biopsies should always be performed, regardless of the endoscopic findings.

RESUMO CONTEXTO: Gastrite é uma afecção muito comum, de larga distribuição mundial, representando uma das entidades patológicas mais prevalentes em Gastroenterologia e Endoscopia Digestiva. OBJETIVO: Este estudo tem por objetivo analisar a correlação entre os achados endoscópicos e o diagnóstico histológico de gastrite antral. MÉTODOS: Nesse estudo, foram analisados 92 laudos de endoscopia digestiva alta, realizados entre novembro de 2014 e janeiro de 2015, que continham biópsia de mucosa gástrica antral, comparando-se os achados endoscópicos e histológicos, que foram classificados segundo o Sistema Sidney. Os 92 exames analisados englobaram 35 homens e 57 mulheres, com idade variando entre 15 e 84 anos. A indicação mais frequente foi epigastralgia. RESULTADOS: Dentre os 92 exames analisados, o diagnóstico histológico de gastrite antral apareceu em 75 exames, sendo que 59 laudos endoscópicos continham o diagnóstico de gastrite antral e 33 laudos endoscópicos foram normais. O coeficiente kappa foi 0,212 com P<0,05, mostrando que não há concordância significativa entre os achados endoscópicos e o diagnóstico histológico de gastrite antral. CONCLUSÃO: Concluímos que a histologia representa o método padrão-ouro para o diagnóstico de gastrite antral, e que na prática clínica diária, biópsias devem ser sempre realizadas, independente dos achados endoscópicos.

Pemphigus Vulgaris in the Mouth and Esophageal Mucosa.

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous disease. In most cases, the initial manifestation occurs in the mouth as multiple ulcerations preceded by blisters that rupture and later spread to other mucous membranes and the skin. Esophageal impairment is rare. We report a case of PV with esophageal involvement in a 53-year-old woman who sought medical care, complaining of diffuse painful lesions in the oral cavity for approximately 1 month, with no improvement with nystatin. Upper digestive endoscopy (UDE) was performed with findings of vesiculobullous lesions in the proximal and middle esophagus, which were biopsied and for which histopathology confirmed PV in the esophageal mucosa. We draw attention to UDE as important for the diagnosis, and it should be indicated in patients with vesiculobullous lesions of the mouth, especially if there are esophageal complaints.