Fructose biphosphate aldolase: A new cassava allergen.

Background: Food allergy has considerably increased in recent years and this situation has been aggravated mainly by the consumption of more processed and complex foods, since minor or potentially allergenic foods are not required to be labeled. Manihot esculenta (cassava) is a widely consumed food in South America, Africa, and Asia and can be used in the production of flour and starch, as well as several other products. This root can cause allergic reactions with symptoms ranging from mild to severe. Methods: Thus, the aim of this study was the characterization of the immunogenic cassava proteins responsible for sensitizing patients allergic to it. Using a 2D-SDS-PAGE based proteomic approach, six proteins were identified, including Fructose Bisphosphate Aldolase (FBA). Recombinant FBA was produced in Expi293 cells and evaluated by immunoblotting with the serum of 10 individual study subjects. Results: Our results showed six cassava IgE-reactive proteins. From those, recombinant fructose bisphosphate aldolase (FBA) showed a positivity of 80% among tested sera, proving to be a highly sensitizing protein. Conclusion: The recombinant FBA molecule obtained in this study can be important for in vivo diagnostic assays, by producing more accurate results, and for desensitization protocols, in which the use of the isolated molecule produces more precise results by avoiding secondary sensitization. Trial registration: All patients signed a consent form approved by the internal ethics committee CAPPesq, Comissão de Ética para Análise de Projetos de Pesquisa do HC FMUSP (CAAE: 10420619.6.0000.0068).

Teste de provocação oral com alimentos: o panorama brasileiro / Oral food challenge: a Brazilian panorama

Introdução: O teste de provocação oral (TPO) com alimentos é o padrão ouro para avaliação diagnóstica e de aquisição de tolerância em pacientes com alergia alimentar (AA). Exige, no entanto, equipe especializada e local apropriado para execução, uma vez que reações alérgicas, incluindo anafilaxia, podem acontecer. Foi recém-incorporado como procedimento reconhecido pelo Sistema Único de Saúde e pela Agência Nacional de Saúde, mas apenas no contexto da alergia ao leite de vaca para pacientes com até 24 meses de vida. Pouco se sabe sobre sua disponibilidade/execução no território brasileiro. Objetivos: Explorar o perfil de realização de TPO com alimentos em âmbito nacional, bem como as limitações para a sua não realização. Métodos: Inquérito virtual foi disponibilizado por e-mail aos 2.500 sócios cadastrados na Associação Brasileira de Alergia e Imunologia questionando sobre a prática de TPO, formação do profissional, limitações para sua não realização e possíveis soluções para sua execução. Resultados: Foram obtidas 290 respostas (11,6% dos associados), sendo a maioria deles proveniente da Região Sudeste (56,1%). Realizam TPO 54,5% (158/290) dos associados, 62% destes mais de 5 TPOs/mês, principalmente para leite e ovo. A execução de TPO na atualidade, majoritariamente na rede privada, esteve associada à prática do procedimento durante a especialização. Falta de recurso e ambiente apropriados são as maiores limitações para a não realização do TPO. Conclusões: Apesar do viés de seleção inerente à metodologia empregada do estudo, este inquérito pioneiro em território nacional tem importância por esclarecer e discutir a realização do TPO no âmbito do Brasil. Certamente este procedimento ainda é insuficientemente realizado no Brasil.

Background: Oral food challenge (OFC), the gold standard for diagnosing food allergy and determining tolerance levels, requires specialized staff and appropriate conditions since anaphylaxis may occur. In 2022, OFC was officially recognized in Brazilian public and private health systems, although only for milk allergy in children up to 24 months of age. Little is known about OFC practices in Brazil. Objectives: To explore OFC practices, barriers, and solutions among Brazilian allergists and immunologists. Methods: A survey was e-mailed to 2500 associates of the Brazilian Association of Allergy and Immunology regarding OFC practices, training experiences, barriers to this procedure, and workable solutions. Results: A total of 290 associates responded (11.6%), more than a half of whom (56.15) practiced in the southeast region: 158 (54.5%) reported performing OFC, of whom 62% performed > 5 procedures each month, mostly for cow milk and hen egg. OFCs were mostly performed in private practice and were associated with specialized training. Lack of an appropriate setting was seen as the main barrier to performing the procedure. Conclusions: Although this study's methodology involves intrinsic biases, this is the first exploration of OFC practice in Brazil. OFCs are still underperformed nationwide.

Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo.

BACKGROUND: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing. CASE PRESENTATION: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome. CONCLUSIONS: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.

Introdução dos alimentos no primeiro ano de vida e prevenção da alergia alimentar: quais as evidências? / Introduction of food in the first year of life and food allergy prevention: what is the evidence?

Objetivo: A incidência das doenças alérgicas cresceu nas últimas décadas. Na tentativa de conter o aumento da alergia alimentar (AA) ao longo dos anos, estratégias de prevenção vêm sendo implementadas. Para promover um melhor entendimento dos dilemas que permeiam a introdução alimentar no primeiro ano de vida, esse artigo trata de uma revisão bibliográfica narrativa sobre a introdução dos alimentos complementares no primeiro ano de vida e possíveis associações com a prevenção primária da alergia alimentar. Fonte dos dados: Publicações relevantes foram pesquisadas nas bases de dados Cochrane Library, MEDLINE, PubMed, Guidelines International Network, National Guidelines Clearinghouse e revisadas recomendações do guia e do consenso nacional de alergia alimentar. Resultados: Estudos observacionais diversos e ensaios clínicos randomizados estão disponíveis, bem como recomendações publicadas por organizações científicas; no entanto, de qualidade variável. Foram consideradas as recomendações de diretrizes de prática clínica classificadas como de alta qualidade e publicações recentes ainda não categorizadas de forma sistemática em sua qualidade, mas internacionalmente reconhecidas como relevantes para a atenção primária. Conclusão: Até o momento, não há evidências consistentes de que a introdução precoce, antes dos 6 meses, dos alimentos alergênicos, contribua para a prevenção de alergia a alimentos na população geral.

Objective: The incidence of allergic diseases has increased in recent decades. In an attempt to contain the increase in food allergy (AA) over the years, prevention strategies have been implemented. To promote a better understanding of the dilemmas that permeate the introduction of food in the first year of life, this article deals with a narrative literature review on the introduction of complementary foods in the first year of life and possible associations with the primary prevention of food allergy. Data source: Relevant publications were searched in the Cochrane Library, MEDLINE, PubMed, Guidelines International Network, National Guidelines Clearinghouse, and revised recommendations from the national food allergy guide and consensus. Results: Several observational studies and randomized controlled trials are available, as well as recommendations. published by scientific organizations; however, of variable quality. Recommendations from clinical practice guidelines classified as high quality and recent publications not yet systematically categorized in their quality, but internationally recognized as relevant to primary care, were considered. Conclusion: To date, there is no consistent evidence that the early introduction, before 6 months, of allergenic foods contributes to the prevention of food allergy in the general population.

Mathematical modeling of the transmission of SARS-CoV-2-Evaluating the impact of isolation in São Paulo State (Brazil) and lockdown in Spain associated with protective measures on the epidemic of CoViD-19.

Coronavirus disease 2019 (CoViD-19), with the fatality rate in elder (60 years old or more) being much higher than young (60 years old or less) patients, was declared a pandemic by the World Health Organization on March 11, 2020. A mathematical model considering young and elder subpopulations under different fatality rates was formulated based on the natural history of CoViD-19 to study the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The model considered susceptible, exposed, asymptomatic, pre-symptomatic, mild CoViD-19, severe CoViD-19, and recovered compartments, besides compartments of isolated individuals and those who were caught by test. This model was applied to study the epidemiological scenario resulting from the adoption of quarantine (isolation or lockdown) in many countries to control the rapid propagation of CoViD-19. We chose as examples the isolation adopted in São Paulo State (Brazil) in the early phase but not at the beginning of the epidemic, and the lockdown implemented in Spain when the number of severe CoViD-19 cases was increasing rapidly. Based on the data collected from São Paulo State and Spain, the model parameters were evaluated, and we obtained a higher estimation for the basic reproduction number R0 (9.24 for São Paulo State, and 8 for Spain) compared to the currently accepted estimation of R0 around 2 using the SEIR (susceptible, exposed, infectious, and recovered compartments) model. In comparison with the lockdown in Spain, the relatively early adoption of the isolation in São Paulo State resulted in enlarging the period of the first wave of the epidemic and delaying its peak. The model allowed to explain the flattening of the epidemic curves by quarantine when associated with the protective measures (face mask, washing hands with alcohol and gel, and social distancing) adopted by the population. The description of the epidemic under quarantine and protections can be a background to foreseen the epidemiological scenarios from the release strategies, which can help guide public health policies by decision-makers.

Modeling the transmission of the new coronavirus in São Paulo State, Brazil-assessing the epidemiological impacts of isolating young and elder persons.

We developed a mathematical model to describe the new coronavirus transmission in São Paulo State, Brazil. The model divided a community into subpopulations composed of young and elder persons considering a higher risk of fatality among elder persons with severe CoViD-19. From the data collected in São Paulo State, we estimated the transmission and additional mortality rates. Based on the estimated model parameters, we calculated the basic reproduction number $R_{0}$, and we retrieved the number of deaths due to CoViD-19, which was three times lower than those found in the literature. Considering isolation as a control mechanism, we varied the isolation rates in the young and elder subpopulations to assess the epidemiological impacts. The epidemiological scenarios focused mainly on evaluating the reduction in the number of severe CoViD-19 cases and deaths due to this disease when isolation is introduced in a population.

Hiperplasia gengival durante uso de ciclosporina / Gingival hyperplasia during cyclosporine use

Paciente do sexo masculino, com 24 anos, portador de dermatite atópica desde o primeiro ano de vida. Começou a evoluir com forma grave da dermatite atópica aos 17 anos, e devido à refratariedade clínica ao tratamento convencional tópico, foi encaminhado para serviço de referência. Após otimizar os cuidados com uso de emolientes, corticoides tópicos e cursos de antibioticoterapia, manteve persistência de eczema generalizado, com SCORAD oscilando entre 40 e 50 no período de 4 meses. Dessa forma, optou-se por terapia sistêmica, sendo iniciado o uso de ciclosporina oral na dose de 200 mg. A resposta terapêutica com a ciclosporina foi percebida após 4 semanas, sendo refletida na redução do escore de gravidade (SCORAD=10). Durante o seguimento, além da melhora clínica, eram monitorados potenciais eventos adversos. O paciente fez uso da ciclosporina durante 5 anos sem apresentar eventos adversos, com necessidade de aumento de dose para 300 mg/dia dois anos após início da medicação. Porém, neste quinto ano de uso da ciclosporina, o paciente apresentou hipertrofia gengival importante. Assim, optou-se por reduzir a dose de ciclosporina de 300 para 200 mg/dia. Nenhum outro sinal ou sintoma foi observado, e os exames laboratoriais também não mostraram qualquer toxicidade. O paciente se mostrou resistente à redução da medicação, pois o temor de piora das lesões de pele o aflige muito. Orientamos sobre a necessidade de melhorar a higiene bucal de forma disciplinada, e agendamos reavaliação clínica mensal. Além disso, foi encaminhado para avaliação odontológica.

A 24-year-old man had atopic dermatitis since the first year of life. He first developed a severe form of atopic dermatitis at the age of 17, and because of clinical refractoriness to conventional topical treatment, he was referred to an excellence center. After care was optimized with emollients, topical corticosteroids and courses of antibiotic therapy, generalized eczema persisted, with Scoring Atopic Dermatitis (SCORAD) score oscillating between 40 and 50 in a period of 4 months. Thus, systemic therapy was chosen, with use of oral cyclosporine at a dose of 200 mg. Therapeutic response with cyclosporine was observed after 4 weeks, with a reduction in the severity score (SCORAD = 10). During followup, in addition to clinical improvement, potential adverse events were monitored. The patient used cyclosporine for 5 years with no adverse events, requiring a dose increase to 300 mg 2 years after initiating the medication. However, in the 5th year of cyclosporine use, the patient had significant gingival hyperplasia. Thus, we decided to reduce the dose of cyclosporine from 300 to 200 mg. No other signs or symptoms were observed and laboratory tests also showed no toxicity. The patient was resistant to reducing the medication, as he feared the skin lesions would aggravate. We advised him on the need to improve oral hygiene in a disciplined manner and scheduled a monthly clinical reevaluation. In addition, he was referred to dental evaluation.

Efeitos adversos do uso de ciclosporina em pacientes com dermatite atópica grave / Adverse effects of using cyclosporine in patients with severe atopic dermatitis

Introdução: A dermatite atópica (DA) é uma doença inflamatória da pele, multifatorial, crônica e recorrente, caracterizada por lesões eczematosas e prurido intenso. Nos casos graves refratários aos tratamentos tópicos, tem se utilizado imunossupressão sistêmica para o controle da doença, sendo a ciclosporina considerada por muitos como terapia de escolha. Este estudo visa avaliar a incidência e gravidade dos eventos adversos relacionados ao uso de ciclosporina em pacientes com DA grave. Métodos: Estudo retrospectivo observacional com análise de prontuários de pacientes com dermatite atópica grave em uso de ciclosporina atendidos em hospital terciário no período de 3 anos. Resultados: Avaliados 80 pacientes com dermatite atópica grave usando ciclosporina, com média de idade de 25,5 anos e 41 do sexo feminino (51,3%). Foram relatados eventos adversos em 25 pacientes. O tempo médio de uso de ciclosporina no grupo com eventos adversos foi de 29,3 meses. Os eventos de maior gravidade foram alteração da função renal e hipertensão, sendo mais observados nos casos de doença mais refratária, quando o uso de ciclosporina foi muito prolongado, superior a 60 meses. As reações evidenciadas foram: hipertensão arterial 40%, alteração renal 20%, náuseas/vômitos 16%, cefaleia 12%, herpes de repetição 12% e outros 4%. Os eventos adversos normalizaram após suspensão da ciclosporina. Conclusão: Pacientes com dermatite atópica grave que usaram ciclosporina por tempo prolongado tiveram maior frequência de eventos adversos potencialmente graves. Todos os efeitos adversos normalizaram após a suspensão de medicação.

Rationale: Atopic dermatitis (AD) is an inflammatory, multifactorial, chronic, recurrent skin disease characterized by eczematous lesions and intense itching. In severe cases refractory to topical treatments, systemic immunosuppression has been used to control the disease, and cyclosporine is largely considered firstline therapy. This study aims to assess the incidence and severity of adverse events related to the use of cyclosporine in patients with severe AD. Methods: This retrospective observational study analyzed medical records of patients with severe atopic dermatitis using cyclosporine treated at a tertiary hospital over a 3-year period. Results: Eighty patients with severe atopic dermatitis using cyclosporine were evaluated. Their mean age was 25.5 years, and 41 (51.3%) were female. Adverse events were reported in 25 patients. The mean duration of cyclosporine treatment in the group with adverse events was 29.3 months. The most serious events were changes in renal function and hypertension, which were most often observed in cases of more refractory disease, when the use of cyclosporine was very prolonged (over 60 months). The adverse reactions were hypertension (40%), renal changes (20%), nausea/vomiting (16%), headache (12%), recurrent herpes (12%) and others (4%). Adverse events were under control after cyclosporine was discontinued. Conclusion: Patients with severe atopic dermatitis who used cyclosporine for a long time had a higher frequency of potentially serious adverse events. All adverse effects were under control after discontinuation of medication.

Hemorragia digestiva alta como complicação de esofagite eosinofílica / Upper gastrointestinal bleeding as a complication of eosinophilic esophagitis

A hemorragia digestiva alta (HDA) é uma condição médica comum, que permanece com uma taxa de mortalidade aproximadamente de 10%. Doenças alérgicas habitualmente não configuram risco para HDA. Entretanto, o aumento recente de doenças alérgicas que afetam cronicamente o trato digestório poderia mudar esse cenário. Este artigo relata um caso de HDA após hematêmese provocada por impactação alimentar. Realizada endoscopia digestiva alta (EDA) e diagnosticada esofagite eosinofílica (EoE), que após tratamento adequado, apresentou melhora dos sintomas. A EoE é uma doença inflamatória crônica esofágica emergente, com aumento do número de casos diagnosticados ao redor do mundo. Atualmente, considera-se a causa mais prevalente de disfagia e impactação alimentar em crianças e adultos jovens. Os sintomas de EoE não são específicos para cada faixa etária, e podem variar desde sintomas mais leves, como sintomas de doença do refluxo gastroesofágico, até disfagia e impactação alimentar. Existe atraso no diagnóstico e tratamento, propiciando um aumento de complicações, cujo risco mais temido seria rotura do esôfago. Revisando a literatura até o presente relato, constatamos que a EoE nunca foi descrita como uma causa de HDA. Além da apresentação incomum da HDA levando ao diagnóstico de EoE, esse caso ressalta a importância do atendimento multidisciplinar e cooperação entre especialidades. Portanto, há necessidade de diagnóstico mais precoce e preciso, buscando ampliar o conhecimento para não negligenciar características específicas da disfagia, e evitar complicações com o tratamento adequado.

Upper gastrointestinal bleeding (UGIB) is a common medical condition whose mortality rate remains at about 10%. Allergic diseases are no usual risk for UGIB. However, the recent increase in allergic diseases that chronically affect the gastrointestinal tract could change this scenario. This article reports a case of UGIB after hematemesis caused by food impaction. Upper gastrointestinal endoscopy was performed and eosinophilic esophagitis (EoE) was diagnosed. EoE is an emerging chronic esophageal inflammatory disease with an increasing number of diagnosed cases around the world. Currently, it is considered the most prevalent cause of dysphagia and food impaction in children and young adults. EoE symptoms are not specific to each age group and may range from mild symptoms such as those of gastroesophageal reflux disease to dysphagia and food impaction. There is a delay in diagnosis and treatment that leads to increased complications, including esophageal rupture, the most feared risk. Our literature review showed that EoE had never been described as a cause of UGIB. In addition to the unusual presentation of UGIB leading to the diagnosis of EoE, this case highlights the importance of multidisciplinary care and cooperation between specialties. Therefore, there is a need for earlier and more accurate diagnosis, which would lead to expanded knowledge that could be used to not disregard specific characteristics of dysphagia and avoid complications with appropriate treatment.

Unveiling atopic dermatitis burden in Brazil: a report from clinical assistance perspective / Revelando a dermatite atópica no Brasil: um relato da perspectiva da assistência clínica

Objective: Atopic dermatitis (AD) or atopic eczema is a chronic skin inflammatory disease that involves the interaction between immune, genetic and environmental triggers. AD affects 15%-20% of infants and 1%-4% of adults worldwide although prevalence varies per country. The main objective is to raise the awareness of AD impact on patients' quality of life (QoL) in Brazil. Methods: Interviews were carried out with key Therapeutic Area Experts (TAEs) throughout the country to gain information about disease management, treatment efficacy and patient's QoL. For disease cost estimation, private health costs from public sources was used. Results: AD prevalence in adults was estimated at 7% in Brazil, of which 35% was moderate and 30% severe AD. Overall, 41% of patients have undergone 5 or more different treatments. However, 17% and 29% of patients with moderate and severe AD, respectively, fail to control their disease. Emollients and topical steroids are the main first-line (1L) treatments for all AD patients, although in the case of moderate and severe AD, a rapid 2-week treatment transition from 1L to 2L has been reported. In terms of economic burden, for severe and moderate AD patients, direct medical costs (medical appointments, treatments, hospitalizations and others) are between 94% and 93%. Regarding indirect costs, absenteeism was estimated to be responsible for 6% and 7% of total cost in moderate and severe AD patients, respectively. Conclusion: There is a need for AD treatments that can be used in the long term without severe side effects and with a positive impact on QoL.

Objetivo: A dermatite atópica (DA) ou eczema atópico é uma doença inflamatória que envolve a interação entre fatores imunológicos, genéticos e ambientais. A DA afeta 15% a 20% das crianças e 1% a 4% dos adultos. O objetivo é conscientizar sobre o impacto da DA na qualidade de vida (QdV) dos pacientes no Brasil. Métodos: Entrevistas foram conduzidas com Especialistas dessa Área Terapêutica (EATs) em todo o país para obter informações sobre o manejo da doença, eficácia do tratamento e QdV dos pacientes. Para estimativa dos custos da doença, utilizamos custos da saúde privada de fontes públicas. Resultados: A prevalência de DA em adultos foi estimada em 7% no Brasil, dos quais 35% possuem DA moderada e 30%, severa. No geral, 41% dos pacientes foram submetidos a cinco ou mais tratamentos diferentes. No entanto, 17% e 29% dos pacientes com DA moderada/grave, respectivamente, não conseguem controlar sua doença. Emolientes e esteroides tópicos são os principais tratamentos de primeira linha (1L) para todos os pacientes. No caso de DA moderada/grave, a transição rápida do tratamento de 1L para 2L em duas semanas é relatada. Em termos de carga econômica, para pacientes com DA grave e moderada, entre 94% e 93% são custos médicos diretos (consultas médicas, tratamentos, hospitalizações e outros). Considerando custos indiretos, o absenteísmo é responsável por 6% e 7% do custo total em pacientes com DA moderada e grave, respectivamente. Conclusão: Em conclusão, há necessidade de tratamentos de DA que possam ser usados a longo prazo sem efeitos colaterais graves e com impacto positivo na qualidade de vida.

Dieta de restrição à proteína do leite de vaca: aderência e rotulagem dos alérgenos / Cow's milk protein elimination diet: adherence and allergen labeling

Introdução: Alergia alimentar é uma grande preocupação de saúde pública, pois afeta 3-5% dos adultos e 8% das crianças mundialmente. Alergia à proteína do leite de vaca (APLV) é a alergia alimentar mais comum em crianças. Reações alérgicas graves e fatais podem ocorrer em qualquer idade, e o tratamento consiste em remover o leite de vaca e seus derivados da dieta. A rotulagem adequada dos alimentos fornece informações sobre os ingredientes alergênicos. Objetivos: Avaliar a eficácia da dieta de eliminação em pacientes com APLV IgE-mediada e características dos sintomas após exposição acidental. Método: Estudo prospectivo com portadores de APLV IgE-mediada atendidos no Serviço de Imunologia Clínica e Alergia do HC-FMUSP, sob dieta de restrição à proteína do leite de vaca. Os pacientes foram avaliados inicialmente através de entrevista oral e por contato telefônico, após 6 meses. Este estudo foi realizado antes que os atuais regulamentos brasileiros de rotulagem de alimentos entrassem em vigor. Resultados: Foram incluídos 23 pacientes. A idade média foi de 10,1 anos, e 14 (60,8%) eram do sexo masculino. Após 6 meses, 7 apresentaram reação alérgica após exposição acidental. Destes, 2 apresentaram reações graves após contato com baixos níveis de proteínas do leite. Os cuidadores de todos os pacientes confirmaram fazer leitura regular dos rótulos. No primeiro contato, 14 pacientes estavam sob restrição de alimentos com a informação "pode conter traços de leite" nos rótulos. Após 6 meses, apenas 7 ainda estavam mantendo esta restrição. Conclusão: Um grupo de pacientes permaneceu com dieta de restrição, inclusive a traços de leite, reiterando a importância da padronização e transparência em relação aos ingredientes alergênicos nos rótulos. Algumas reações ocorreram após a ingestão de alimentos derivados do leite, enfatizando a necessidade de reforço periódico da adesão à dieta de restrição e da prevenção em situações de risco, como festas e escola.

Introduction: Food allergy is a major public health concern, as it affects up to 3-5% of adults and 8% of children worldwide. Cow's milk protein allergy (CMPA) is the most common food allergy in young children. Severe and fatal allergic reactions may occur at any age, and treatment consists of removing cow's milk and its derivatives from the diet. Proper food labeling provides clear and accurate information about allergenic ingredients. Objectives: To evaluate the effectiveness of an elimination diet in IgE-mediated CMPA patients and features of symptoms after accidental exposure. Method: A prospective study with IgE-mediated CMPA patients treated at HC-FMUSP Clinical Immunology and Allergy Service, undergoing a cow's milk protein elimination diet. The patients were first evaluated through oral interview, then by telephone contact after 6 months. This study was conducted before current Brazilian food labeling regulations came into effect. Results: Twenty-three patients were enrolled. The mean age was 10.1 years, and 14 (60.8%) were male. After 6 months, 7 patients presented with allergic reaction after accidental exposure. Of those, 2 presented with severe reactions after exposure to low levels of milk protein. All patients' caregivers confirmed they read labels regularly. At the first contact, 14 patients were under restriction of foods which read "may contain traces of milk" on their label. After 6 months, 7 patients were still under such restriction. Conclusion: A group of patients still needed an elimination diet, including traces of milk, reinforcing the importance of standardization and transparency regarding allergenic ingredients in all labels. Some reactions occurred after intake of milk derivatives, emphasizing the need for periodic reinforcement of adherence to elimination diet and prevention in potentially risky situations, such as at parties and at school.

Efetividade das técnicas de restauração de barreira cutânea "Wet Wraps" e "Soak and Smear" na dermatite atópica grave: relato de caso e revisão da literatura / Effectiveness of skin barrier repair techniques "Wet Wraps" and "Soak and Smear" in severe atopic dermatitis: a case report and literature review

A restauração da barreira cutânea é o primeiro passo para o controle da dermatite atópica (DA) em todas as suas formas. O tratamento da DA grave ou refratária em crianças apresenta alguns desafios, devido principalmente aos efeitos colaterais das drogas imunossupressoras. Como alternativa, as técnicas "Wet Wraps" e "Soak and Smear" são intervenções seguras e eficazes em casos em que a xerose é fator determinante de agravamento da doença. Relata-se o caso de um menino de 5 anos com DA grave (SCORAD = 54) não controlada, com prurido intenso e distúrbio do sono. Houve tratamento prévio com corticoide tópico e sistêmico, diversos emolientes, uso repetido de antibióticos tópicos e sistêmicos, e restrição de leite de vaca, sem resultado. As comorbidades incluíam rinite alérgica (sensibilizado para ovo, leite, epitélio de cão e ácaros) e transtorno do espectro autista. Foi realizado tratamento tópico com ácido fusídico e corticoide de média potência, além de otimização das técnicas de restauração de barreira cutânea. Após um mês, o paciente retornou com melhora quase completa das lesões, SCORAD de 17 (leve), referindo intensa melhora na qualidade de vida, com resolução do distúrbio do sono. Este caso demonstrou a efetividade das técnicas "Wet Wraps" e "Soak and Smear" em criança com DA grave. A boa adesão e a correta execução são fundamentais para o resultado, ressaltando a importância da atenção médica quanto à educação da equipe e dos pais sobre o tratamento. Essas técnicas são bem estudadas e podem ser realizadas como resgaste na DA grave, mesmo em crianças com alterações comportamentais, e, se adequadamente utilizadas, podem evitar a prescrição de imunossupressores.

Skin barrier repair is the first step to control all forms of atopic dermatitis (AD). Treatment of severe or refractory AD in children poses some challenges, mainly due to the side effects of immunosuppressive drugs. As an alternative treatment, "Wet Wraps" and "Soak and Smear" techniques are safe and effective interventions when xerosis is an aggravating factor of the disease. We report the case of a 5-year-old boy with severe AD (SCORAD = 54), showing severe pruritus and sleep disorder. Prior treatment involved topical and systemic corticosteroids, several emollients, repeated use of topical and systemic antibiotics, and restriction to cow's milk, without any positive result. Comorbidities included allergic rhinitis (sensitized to egg, milk, dog epithelium and mites) and autism spectrum disorder. Topical treatment with fusidic acid and medium-potency corticoid was performed, in addition to optimization of skin barrier repair techniques. After one month, the patient returned with clinical improvement, SCORAD of 17 (mild), reporting a strong improvement in quality of life and no sleep disorder. This case demonstrates the effectiveness of the "Wet Wraps" and "Soak and Smear" techniques when applied to children with severe AD. Good adherence and correct execution are fundamental to outcomes, stressing the importance of medical care in the education of team and parents about the treatment. These techniques are well studied and can be performed as rescue therapy in severe AD, even in children with behavioral disorders, and, if properly used, may avoid prescription of immunosuppressants.

Consenso Brasileiro sobre Alergia Alimentar: 2018 - Parte 1 - Etiopatogenia, clínica e diagnóstico. Documento conjunto elaborado pela Sociedade Brasileira de Pediatria e Associação Brasileira de Alergia e Imunologia / Brazilian Consensus on Food Allergy: 2018 - Part 1 - Etiopathogenesis, clinical features, and diagnosis. Joint position paper of the Brazilian Society of Pediatrics and the Brazilian Association of Allergy and Immunology

A alergia alimentar é definida como uma doença consequente a uma resposta imunológica anômala, que ocorre após a ingestão e/ou contato com determinado(s) alimento(s). Atualmente é considerada um problema de saúde pública, pois a sua prevalência tem aumentado no mundo todo. É um capítulo à parte entre as reações adversas a alimentos, e de acordo com os mecanismos fisiopatológicos envolvidos, essas reações podem ser imunológicas ou não-imunológicas. Em geral, a alergia alimentar inicia precocemente na vida com manifestações clínicas variadas na dependência do mecanismo imunológico envolvido. A anafilaxia é a forma mais grave de alergia alimentar mediada por IgE. Conhecimentos recentes permitiram a melhor caracterização da Síndrome da enterocolite induzida por proteína alimentar (FPIES), assim como da esofagite eosinofílica. Vários fatores de risco, assim como novos alérgenos alimentares, têm sido identificados nos últimos anos. Tomando-se como ponto de partida o "Consenso Brasileiro sobre Alergia Alimentar: 2007" foi realizada revisão e atualização dos conceitos apresentados por grupo de alergologistas, gastroenterologistas, nutrólogos e pediatras especializados no tratamento de pacientes com alergia alimentar. Novos conceitos foram apresentados sobretudo pela melhor caracterização. O objetivo desta revisão foi elaborar um documento prático capaz de auxiliar na compreensão dos mecanismos envolvidos na alergia alimentar, assim como dos possíveis fatores de risco associados à sua apresentação, bem como sobre a sua apresentação clínica.

Food allergy is defined as a disease resulting from an anomalous immune response that occurs after ingestion of and/or contact with certain foods. It is currently considered a public health problem because of its increased prevalence worldwide. Food allergy is a major entity among adverse reactions to foods; depending on the pathophysiological mechanisms involved, these reactions may be immunological or non-immunological. In general, food allergy starts early in life with varied clinical manifestations depending on the immune mechanism involved. Anaphylaxis is the most severe form of IgE-mediated food allergy. Recent knowledge has allowed to better characterize food protein-induced enterocolitis syndrome (FPIES), as well as eosinophilic esophagitis. Several risk factors as well as new food allergens have been identified in recent years. Taking the 2007 Brazilian Consensus on Food Allergy as a starting point, the concepts presented were reviewed and updated by a group of allergologists, gastroenterologists, nutrologists and pediatricians specialized in the treatment of patients with food allergy. The objective of this review was to develop a hands-on document capable of helping improve the understanding of the mechanisms involved in food allergy, possible associated risk factors, as well as clinical presentation.

Consenso Brasileiro sobre Alergia Alimentar: 2018 - Parte 2 - Diagnóstico, tratamento e prevenção. Documento conjunto elaborado pela Sociedade Brasileira de Pediatria e Associação Brasileira de Alergia e Imunologia / Brazilian Consensus on Food Allergy: 2018 - Part 2 - Diagnosis, treatment and prevention. Joint position paper of the Brazilian Society of Pediatrics and the Brazilian Association of Allergy and Immunology

Na última década o conhecimento sobre a etiopatogenia da alergia alimentar (AA) avançou muito. A identificação de novas formas clínicas de apresentação, aliada à aquisição de novos métodos laboratoriais, possibilitaram a realização do diagnóstico etiológico de modo mais preciso, sobretudo quanto à reatividade cruzada entre alimentos e mesmo na identificação de marcadores indicativos de formas clínicas transitórias, persistentes e quadros mais graves. A padronização dos testes de provocação oral permitiu a sua realização de forma mais segura e possibilitou a sua inclusão entre as ferramentas disponíveis para uso na confirmação etiológica da AA. Apesar disso, a exclusão do alimento responsável pelas manifestações clínicas continua sendo a principal conduta terapêutica a ser empregada. Entre os pacientes alérgicos às proteínas do leite de vaca, a disponibilidade de fórmulas especiais, por exemplo parcialmente hidrolisadas, extensamente hidrolisadas à base da proteína do leite de vaca e fórmulas de aminoácidos, tem facilitado o tratamento substitutivo do leite de vaca para esses pacientes. A abordagem atual da anafilaxia é revisada, uma vez que os alimentos são os principais agentes etiológicos em crianças. Avanços na conduta de algumas manifestações gastrintestinais também são abordados. Na atualidade, a imunoterapia oral tem sido cada vez mais utilizada. A aquisição de novos agentes, os imunobiológicos, também são apresentados à luz das evidências científicas e clínicas atuais. Considerações sobre história natural da AA, assim como sobre formas de prevenção da AA também são abordadas. Em conclusão, o Consenso Brasileiro sobre Alergia Alimentar de 2018 objetivou rever os métodos diagnósticos e esquemas de tratamento disponíveis e empregados no acompanhamento de pacientes com AA, visando a melhor abordagem terapêutica desses pacientes.

Over the last decade, knowledge about the etiopathogenesis of food allergy (FA) has advanced a great deal. The identification of new clinical presentations, associated with the acquisition of new laboratory methods, have made the diagnostic process more accurate, especially with regard to cross-reactivity between foods and the identification of biomarkers suggestive of transitory, persistent clinical forms and/or more severe manifestations. The standardization of oral provocation tests has made their performance safer and has allowed their inclusion among the tools available for use in the etiological confirmation of FA. Despite this, exclusion of the food involved in the clinical manifestations remains as the main therapeutic strategy. Among patients allergic to cow's milk proteins, the availability of special formulas, e.g., partially hydrolyzed and extensively hydrolyzed cow's milk protein-based formulas, in addition to amino acid formulas, has facilitated the introduction of substitute formulas for these patients. The current approach to anaphylaxis is reviewed, since food is the major etiological agent in children. Advances in the management of some gastrointestinal manifestations are also addressed. Currently, oral immunotherapy has been increasingly used. The acquisition of new agents, namely, immunobiological agents, is also described in light of current scientific and clinical evidence. Considerations on the natural history of FA, as well as on ways how to prevent FA, are addressed. In conclusion, the 2018 Brazilian Consensus on Food Allergy aimed to review the diagnostic methods and treatment schemes available and used in the follow-up of patients with FA, with a view to adopting the best possible therapeutic approach to these patients.

Eosinophilic Esophagitis: Latent Disease in Patients with Anaphylactic Reaction to Cow's Milk.

BACKGROUND: Food allergy and eosinophilic esophagitis are a substantial and evolving public health issue. Clinicians should know the relationship between these diseases and how one may predispose to the other. This can help minimize misdiagnosis. OBJECTIVE: The objective of this study was to assess esophageal eosinophilia and eosinophilic esophagitis frequency in patients with persistent cow's milk allergy and anaphylaxis manifestations. METHODS: Patients with persistent cow's milk allergy with anaphylaxis manifestations were enrolled from 2012 through 2016 at the São Paulo University Hospital, Brazil. All of them were submitted to endoscopy despite the presence or absence of gastrointestinal symptoms. Demographics data, atopic comorbidities, medication use, endoscopic findings, and esophageal eosinophilia frequency were evaluated. RESULTS: Eighty-nine patients were selected. The median age was 8 years. It was observed that 34 of 89 patients (38.2%; 95% confidence interval [CI]: 28.14%-49.16%) presented with esophageal eosinophilia. Five patients (7.1%) presented proton pump inhibitor-responsive esophageal eosinophilia, and 10 patients (14.2%) presented eosinophilic esophagitis. We found that 29.4% were asymptomatic patients, 23.5% had nonspecific symptoms, 23.5% had persistent typical symptoms, and 23.5% had intermittent typical symptoms. There was an association with inflammatory endoscopy findings in 21 patients (61.7%). CONCLUSIONS: This description demands scientific attention because it is the highest frequency of esophageal eosinophilia yet described in a group of patients with cow's milk allergy presenting with anaphylaxis. Eosinophilic esophagitis is a condition that can coexist "silently" with an IgE-mediated food allergy and is most often underestimated and underdiagnosed.

Relative cost-effectiveness of using an extensively hydrolyzed casein formula in managing infants with cow's milk allergy in Brazil.

OBJECTIVE: To estimate the cost-effectiveness of three alternative dietetic strategies for cow's milk allergy in Brazil: 1) using an extensively hydrolyzed casein formula (eHCF; Nutramigen) as a first-line formula, but switching to an amino acid formula (AAF) if infants remain symptomatic; 2) using an AAF as a first-line formula and then switching to an eHCF after 4 weeks once infants are symptom-free, but switching back to an AAF if infants become symptomatic; and 3) using an AAF as a first-line formula and keeping all infants on that formula. The analysis was conducted from the perspective of the Brazilian public health care system, Sistema Único de Saude. METHODS: Decision modeling was used to estimate the probability of immunoglobulin E (IgE)-mediated and non-IgE-mediated allergic infants developing tolerance to cow's milk by 12 months from starting a formula. The models also estimated the Sistema Único de Saude cost (at 2013/2014 prices) of managing infants over 12 months after starting a formula, as well as the relative cost-effectiveness of each of the dietetic strategies. RESULTS: The probability of developing tolerance to cow's milk by 12 months from starting a formula was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were initially fed with an eHCF, compared with those who were initially fed with an AAF. The total health care cost of initially feeding an eHCF to cow's milk allergic infants was less than that of initially feeding both IgE-mediated and non-IgE-mediated infants with an AAF. CONCLUSION: Within the study's limitations, using an eHCF instead of an AAF for the first-line management of newly-diagnosed infants with cow's milk allergy affords a cost-effective use of publicly funded resources, since it improves the outcome for less cost.

Prevenção e tratamento de alergia alimentar: foco na tolerância oral / Prevention and treatment of food allergy: focus on oral tolerance

O trabalho lembra a incidência cada vez maior da alergia alimentar em todo o mundo e analisa a importância do estímulo a tolerância oral, fenômeno fisiológico capaz de limitar o problema. Destaca a superioridade do leite materno em relação ao de vaca, em virtude das diferenças na respectiva microbiota intestinal. Finalizando, destaca a indicação das fórmulas parcialmente e/ou extensamente hidrolisadas na prevenção e no tratamento das doenças alérgicas, particularmente a alergia ao leite de vaca.

Molecular Diagnosis of Shrimp Allergy: Efficiency of Several Allergens to Predict Clinical Reactivity.

BACKGROUND: The diagnosis of shellfish allergy remains a challenge for clinicians. Several shellfish allergens have been characterized and their IgE epitopes identified. However, the clinical relevance of this sensitization is still not clear. OBJECTIVE: The objective of this study was to identify allergens and epitopes associated with clinical reactivity to shrimp. METHODS: Shrimp-sensitized subjects were recruited and grouped based on the history of shrimp-allergic reactions and challenge outcome. IgE reactivity to recombinant crustacean allergens, and IgE and IgG4 reactivity to peptides were determined. Subjects sensitized to dust mites and/or cockroach without shrimp sensitization or reported allergic reactions, as well as nonatopic individuals, were used as controls. RESULTS: A total of 86 subjects were recruited with a skin prick test to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16 were tolerant. All subjects without a history of reactions had negative challenges. The individuals with a positive challenge more frequently recognized tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test is very likely to result in a positive challenge, though the frequency of recognition is low. Subjects with dust mite and/or cockroach allergy not sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes of these allergens may be important in predicting clinical reactivity. CONCLUSION: Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is associated with clinical reactivity to shrimp. Myosin light chain testing may help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin appear to be cross-reacting allergens between shrimp and arthropods. Detection of IgE to these allergens and some of their epitopes may be better diagnostic tools in the routine workup of shrimp allergy.

Alérgenos recombinantes: papel no diagnóstico e na imunoterapia alérgeno-específica / Recombinant allergens: role in diagnosis and in allergen-specific immunotherapy

Nos últimos 30 anos tem havido um avanço notável na identificação, purificação e expressão recombinante de alérgenos relevantes das mais variadas fontes, incluindo ácaros, insetos, mamíferos, polens, alimentos, fungos, látex e outras fontes. Estes avanços resultaram na utilização crescente de alérgenos purificados, naturais ou recombinantes, para melhorar o diagnóstico de alergia pelos métodos que dispomos, incluindo os testes cutâneos de hipersensibilidade imediata, e os métodos in vitro para medida de anticorpos IgE específicos, como ImmunoCAP, ImmunoCAP-ISAC, ELISA e MARIA. Mais recentemente, o uso de alérgenos recombinantes de pólen de bétula (rBet v 1) e de gramas (coquetel de 5 alérgenos) em imunoterapia foi relatado como seguro e eficaz, com resultados comparáveis aos obtidos usando extratos naturais, em pacientes com rinoconjuntivite alérgicos a polens. No presente artigo, apresentamos revisão atualizada do uso de alérgenos recombinantes em diagnóstico de alergia e em imunoterapia alérgeno-específica, incluindo novas estratégias de imunoterapia. Focalizamos na avaliação crítica de estudos que investigaram sensibilidade, especificidade, reatividade cruzada e valor prognóstico de métodos diagnósticos com uso de alérgenos recombinantes versus extratos naturais; nas recomendações atuais para o uso destes novos métodos na prática clínica; e na revisão de estudos clínicos com imunoterapia usando alérgenos recombinantes realizados até o momento.

Over the past 30 years, a great deal of progress has been made in the identification, purification,and recombinant expression of relevant allergens from various sources, including mites, insects,mammals, pollens, foods, fungi, latex, and other sources. These new developments have resultedin an increasing use of purified allergens, either natural or recombinant, to improve the diagnosisof allergy via the methods currently available, including skin tests and in vitro tests for measuringspecific IgE antibodies, e.g., ImmunoCAP, ImmunoCAP-ISAC, ELISA, and MARIA. More recently,the use of recombinant allergens from birch pollen (rBet v 1) and from grass pollen (a cocktailof five allergens) in immunotherapy has been reported to be safe and effective, with resultscomparable to those obtained with natural extracts in patients with rhino-conjunctivitis due topollen allergy. In the present article, we present an up-to-date review on the use of recombinantallergens in the diagnosis of allergy and in allergen-specific immunotherapy, including newstrategies for immunotherapy. We focus on the critical analysis of studies that have investigatedsensitivity, specificity, cross-reactivity, and the prognostic value of diagnostic methods that includerecombinant allergens versus natural extracts; on current recommendations for the use of thesenew methods in clinical practice; and on the review of clinical studies using immunotherapy withrecombinant allergens performed to date.