Actualización del consenso chileno SOCHINEP-SER para el manejo de las sibilancias recurrentes del preescolar / Update of the chilean consensus SOCHINEP-SER for the management of recurrent wheezing in preschool children

Las sibilancias recurrentes del preescolar son un problema prevalente. 50% de todos los niños tiene al menos un episodio de sibilancias en los primeros 6 años. Sin embargo, solo 4 % de los menores de 4 años tiene diagnóstico de asma. Por este motivo es fundamental realizar una adecuada anamnesis y examen físico tendientes a descartar causas secundarias, lo que debe ser complementado con exámenes de laboratorio de acuerdo con la orientación clínica. En la actualidad se recomienda indicar tratamiento de mantención con corticoides inhalados en aquellos niños que tengan episodios repetidos de obstrucción bronquial y que tengan una alta probabilidad de respuesta favorable a esta terapia. Se ha demostrado que aquellos pacientes que tienen un recuento de eosinófilos en sangre > 300 células por mm3 o aquellos que presentan una prueba cutánea positiva o IgE específicas positivas para alérgenos inhalados, responderán adecuadamente al tratamiento con esteroides inhalados.

Recurrent wheezing in preschoolers has a high prevalence. 50% of all children have at least one wheezing episode in the first six years of life. However, only 4% of children under four years of age are diagnosed with asthma. Therefore, it is essential to carry out an adequate medical history and physical examination to rule out secondary causes, which must be complemented with laboratory tests in accordance with clinical guidance. It is recommended to indicate maintenance treatment with inhaled corticosteroids to those children who have repeated episodes of wheezing and who have a high probability of a good response to this therapy. It has been demonstrated that those patients who have blood eosinophil count > 300 cells per mm3 or those who have a positive skin test or positive specific IgE for inhaled allergens will have a good response to inhaled corticosteroids.

Study on the characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis / 中华预防医学杂志

Objective: To investigate the clinical characteristics of Aspergillus fumigatus(A.f)-sensitized asthma and allergic bronchopulmonary aspergillosis (ABPA), which provides a foundation for the diagnosis and differential diagnosis of A.f-sensitized asthma and ABPA, as well as the prevention of ABPA. Methods: This was a single-center retrospective case-control study. Collected the clinical data of patients who visited the Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University from December 2018 to May 2022.A total of 122 patients were included, including 64 males (52.5%) and 58 females (47.5%).The age range was 3 to 89 years.The median age was 44 years.The average age was 41.8 years.The patients were divided into three groups (48 ABPA, 35 A.f-sensitized asthma and 39 HDM-sensitized asthma).Analyzed the differences and correlations among clinical indicators in the three groups, and evaluated the risk factors for the development of ABPA in A.f-sensitized asthma.For statistical analysis, metrological data was tested by t-test or Wilcoxon Mann-Whitney. Classification variables by chi-square test or Fisher's exact test. Pearson correlation analysis for normal distribution data.Spearman correlation analysis for skewed distribution data. Influencing factor analysis was performed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was made, the area under the ROC curve (AUC) was calculated, and the sensitivity and specificity of the model were evaluated. Results: Compared with patients with A.f-sensitized asthma, the fractional exhaled nitric oxide (FeNO) [75.00(52.00, 87.00)ppb vs. 40.00(32.00, 52.00)ppb], eosinophils% (EO%) [10.60(6.75, 13.05) vs. 4.10(1.20, 7.30)], eosinophils (EO) [1.50(1.07, 2.20)×109/L vs. 0.33(0.10, 0.54)×109/L], A.f-specific Immunoglobulin E (sIgE) [10.24(4.09, 22.88)KU/L vs. 1.13(0.53, 3.72) KU/L], and sIgE to total IgE(tIgE) ratio (sIgE/tIgE) [0.0049(0.0027, 0.0100) vs. 0.0008(0.0004, 0.0017)] were higher in ABPA patients, the differences were statistically significant (P<0.001). In all patients, tIgE was positively correlated with EO% (r=0.206, P<0.05) and EO (r=0.302, P<0.001). sIgE/tIgE was negatively correlated with one-second rate (FEV1/FVC%) (r=-0.256, P<0.01). The percentage of predicted forced vital capacity [FVC(%)] was negatively correlated with FeNO (r=-0.184, P<0.05).In the ABPA group, the percentage of predicted peak expiratory flow [PEF(%)] was negatively correlated with FeNO (r=-0.295, P<0.05). In the HDM-sensitized asthma group, FeNO was positively correlated with EO% (r=0.49, P<0.01) and EO (r=0.548, P<0.001).The results of logistic regression analysis showed that FeNO and EO were the influencing factors for the development of ABPA in A.f-sensitized asthma. ROC curve analysis results showed that A.f-sIgE (cut-off, 4.108; AUC=0.749;95%CI, 0.632-0.867), sIgE/tIgE(cut-off, 0.0026;AUC=0.749;95%CI, 0.631-0.868), FeNO(cut-off, 55.5;AUC=0.794; 95%CI, 0.687-0.900), EO% (cut-off, 8.70;AUC=0.806;95%CI, 0.709-0.903) and EO (cut-off, 0.815;AUC=0.865;95%CI, 0.779-0.950) had differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% had good diagnostic efficiency in differentiating A.f-sensitized asthma from ABPA, with a sensitivity of 91.4% and a specificity of 84.4%. Conclusion: Compared with patients with A.f-sensitized asthma, patients with ABPA have more severe eosinophil inflammation. The higher the FeNO and EO, the more likely A.f-sensitized asthma will develop into ABPA.sIgE/tIgE may have differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% has good diagnostic efficacy in differentiating A.f-sensitized asthma from ABPA.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

The advances of allergen component detection in IgE-mediated food allergy / 中华预防医学杂志

There are many types in food allergy, and the most common is mediated by IgE. Currently, the diagnosis of food allergy mainly relied on skin prick test and serum specific IgE of allergen extract, which can not identify cross-sensitization. Component-resolved diagnosis (CRD) can identify the major allergen components and cross-components of food allergens, which plays an important role in dietary guidance, prognosis monitoring and diagnosis of special types of IgE-mediated food allergy. This article enumerates clinical characteristics of the IgE-mediated common food allergies, such as milk, egg and seafood allergy, and special type of food allergy, such as cat pork syndrome, oral allergy syndrome, α-gal syndrome and food-dependent exercise-induced anaphylaxis, summarizes the advances of CRD in these types of IgE-mediated food allergy, in order to provide an evidence for the diagnosis, treatment and prevention of IgE-mediated food allergy.

Analysis of related factors for postoperative recurrence of antrochoanal polyps in children / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the correlation between nasal resistance and lung function in children with allergic rhinitis（AR）, and explore whether AR children with increased nasal resistance are accompanied by potential lower respiratory tract involvement. Methods:A total of 88 children diagnosed with AR from December 2021 to December 2022 were selected as the study group, while 20 normal children were selected as the control group during the same period. Both the study group and the control group children underwent lung function tests, bronchodilator tests, and nasal resistance measurements. Spearman correlation analysis and multiple linear regression analysis were performed on the results of nasal resistance and lung function tests to explore the relationship and influencing factors between the two groups.According to the results of nasal resistance measurement, children with increased nasal resistance and abnormal lung function were divided into a mild increase in nasal resistance with abnormal lung function group and a moderate to severe increase in nasal resistance with abnormal lung function group. The degree of increased nasal resistance was analyzed to determine whether it would affect lung function. Results:The FEF25, FEF50, and FEF75 levels in the study group were significantly lower than those in the control group（P<0.05）. The FEV1of children with moderate to severe increase in AR nasal resistance was significantly lower than that of children with mild increase in AR nasal resistance（P<0.05）. There was a correlation between nasal resistance and FEV1/FVC, R20 in AR children, and FEV1/FVC, R20 were the influencing factors of nasal resistance in AR children（P<0.05）. There was no correlation between total serum IgE, lung function, and bronchodilation test in AR patients（P>0.05）. Conclusion:The nasal ventilation function of AR patients has changed, and there is a downward trend in small airway function. Children with moderate to severe increase in AR nasal resistance have a more significant decrease in lung ventilation function than those with mild increase. The nasal resistance of AR children is influenced by FEV1/FVC and R20, and FEV1/FVC and R20 decrease as the nasal resistance value increases. The improvement rate of lung function and FEV1 are not influencing factors for the elevation of total serum IgE.

Administration of a single chain variable fragments chimeric protein (SD) of ovalbumin epitopes internalizing receptor DEC-205 antibody inhibits food allergy in mice / 细胞与分子免疫学杂志

Objective To investigate the preventive therapeutic effect and possible mechanism of single chain variable fragments chimeric protein (SD) of ovalbumin epitopes internalizing receptor DEC-205 antibody on food allergy in mice. Methods Mice were randomly divided to five groups (control, PBS, scFv DEC 100 μg, SD 50 μg, SD 100 μg) and treated for 24 hours before OVA administration. After challenge, the serum level of OVA-specific IgE, IgG1, IgG2a and IL-4 were detected by ELISA. Infiltration of eosinophils and mast cells in the jejunum was observed by HE staining and toluidine blue staining respectively. The bone marrow of tibia and femur was isolated and cultured to obtain immature dendritic cells(BMDCs), which were further treated with LPS (10 ng/mL), TSLP (50 ng/mL), scFv DEC protein (1000 ng/mL) and SD protein (10,100,1000)ng/mL for 24 hours, and the IL-10 level of supernatant was assayed by ELISA. Results Compared with PBS group, the number of SD-treated mice with diarrhea was markedly reduced. The difference in rectal temperature and the levels of serum OVA-specific IgE, IgG1, IgG2a and IL-4 decreased significantly after prophylactic administration of SD; The number of eosinophils and mast cells in jejunum also decreased significantly while the IL-10 level in the supernatant of BMDCs increased significantly after SD intervention. Conclusion SD mitigates experimental FA response by fosters the immune tolerance property of dendritic cells.

Dermatite atópica grave: guia prático de tratamento da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Severe atopic dermatitis: a practical treatment guide from the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

A dermatite atópica (DA) é uma doença cutânea inflamatória, crônica, comum, complexa e de etiologia multifatorial, que se manifesta clinicamente com prurido muitas vezes incapacitante, lesões recorrentes do tipo eczema, xerose e que pode evoluir para liquenificação. Embora o conhecimento sobre a sua fisiopatologia venham crescendo nos últimos anos, ainda as formas graves são frequentes e representam um desafio para o clínico. Para o presente guia realizou-se revisão não sistemática da literatura relacionada à DA grave refratária aos tratamentos habituais com o objetivo de elaborar um documento prático e que auxilie na compreensão dos mecanismos envolvidos na DA, assim como dos possíveis fatores de risco associados à sua apresentação. A integridade da barreira cutânea é um dos pontos fundamentais para a manutenção da homeostase da pele. Além dos cuidados gerais: evitação dos agentes desencadeantes e/ou irritantes, o uso de hidratantes, suporte emocional, entre outros, o uso de agentes anti-inflamatórios/imunossupressores de uso tópico e/ou sistêmico também foi revisado. A aquisição de novos agentes, os imunobiológicos e as pequenas moléculas, melhorou a terapêutica para os pacientes com formas graves de DA, sobretudo as refratárias aos tratamentos convencionais.

Atopic dermatitis is a chronic, common, and complex inflammatory skin disease with a multifactorial etiology. It manifests clinically with often disabling pruritus, recurrent eczema-like lesions, and xerosis, and can progress to lichenification. Although understanding of the disease's pathophysiology has been growing in recent years, severe forms are still frequent and represent a challenge for clinicians. A non-systematic review of the literature on severe atopic dermatitis refractory to conventional treatment was conducted to develop the present guide, whose purpose is to help clarify the mechanisms involved in the disease and possible risk factors. The integrity of the skin barrier is fundamental for maintaining skin homeostasis. In addition to general care, patients should avoid triggering and/or irritating agents and moisturizers and seek emotional support, etc.; the use of topical and/or systemic anti-inflammatory/immunosuppressive agents was also reviewed. New agents, immunobiologicals, and small molecules have led to a broader range of therapies for patients with severe forms of the disease, especially cases refractory to conventional treatment.

Polinose no Rio de Janeiro é possível? Relato de caso / Is pollinosis in Rio de Janeiro possible? Case report

A polinose é uma doença comum dos países de clima temperado, onde as estações do ano são bem definidas. Apresenta-se clinicamente como rinoconjuntivite e/ou asma sazonal ou perene com exacerbação na primavera. No Brasil, há relatos de casos de polinose por polens de gramíneas que são os principais causadores dessa patologia, principalmente na Região Sul, apesar do clima subtropical. A expansão da população e desmatamento com crescente urbanização de áreas florestais são alguns dos responsáveis pelo aumento de casos em vários locais do país. Neste relato de caso, descrevemos um caso de polinose por polens de gramínea em um paciente militar que morou em países da Europa e que atualmente reside em uma zona de mata nativa no Rio de Janeiro, RJ, Brasil. Apesar de a polinose não ser uma doença encontrada no RJ, este diagnóstico não deve ser excluído em pacientes com conjuntivite/rinoconjuntivite sazonal, principalmente quando têm uma história pregressa de morar vários anos fora país.

Pollinosis is a common disease in temperate countries, which have well-defined seasons. It presents clinically as rhinoconjunctivitis and/or seasonal or perennial asthma that is exacerbated in spring. In Brazil, cases of pollinosis due to grass pollens have been reported, especially in the south, despite its subtropical climate. The expansion of the population and deforestation, including increasing urbanization of forest areas, are contributing to the rise in cases in various regions of the country. This case report describes a case of pollinosis due to grass pollens in a military patient who lived in Europe and currently resides in a region of native forest in Rio de Janeiro metropolitan area. Although pollinosis is not found in the state of Rio de Janeiro, this diagnosis should not be excluded in patients with seasonal conjunctivitis/ rhinoconjunctivitis, especially when they have lived outside the country for several years.

Alergia alimentar não IgE mediada: proctocolite induzida por proteínas alimentares ­ Atualização / Non-IgE mediated food allergy: food protein-induced allergic proctocolitis ­ An update

Nas últimas décadas observa-se aumento na prevalência mundial de alergia alimentar, que já acomete aproximadamente 6% das crianças, atribuído à interação entre fatores genéticos, ambientais e alterações na resposta imunológica e pode envolver reações mediadas por IgE, não mediadas e mistas. As formas não IgE mediadas decorrem de reação de hipersensibilidade tardia, mediada por linfócitos T e afetam prioritariamente o trato gastrointestinal, como a Síndrome da enterocolite induzida por proteína alimentar (FPIES), Síndrome da proctocolite alérgica induzida por proteína alimentar (FPIAP), Síndrome da enteropatia induzida por proteína alimentar (FPE) e doença celíaca. As características destas reações podem ser diferenciadas por sua apresentação clínica, gravidade, idade de início e história natural. Entre as reações alérgicas aos alimentos não IgE mediadas, a proctocolite alérgica é a mais frequente. Geralmente ocorre no primeiro ano de vida e apresenta excelente prognóstico. Embora costume ter um curso benigno, traz grande preocupação aos cuidadores por frequentemente cursar com quadro de hematoquezia exigindo diagnóstico diferencial adequado. O conhecimento e manejo da proctocolite alérgica é de suma importância para a prática médica em Alergia e Imunologia. Seu diagnóstico é baseado na história clínica seguindo-se dieta de exclusão, especialmente do leite de vaca, com subsequente provocação oral, que geralmente pode ser realizada no domicílio. O diagnóstico preciso é importante, para se evitar dietas de exclusão desnecessárias. Nesta revisão foram utilizados artigos publicados nos últimos anos, com busca realizada através da base PubMed envolvendo revisões, diagnóstico e tratamento de alergias não IgE mediadas, com foco em proctocolite alérgica.

An increase in the worldwide prevalence of food allergies has been observed in the past decades, currently affecting 6% of children. This increase has been associated with the interaction between genetic, environmental, and immune response factors and can be observed in IgE, non-IgE, and mixed mediated reactions. Non-IgE mediated food allergies result from delayed-type hypersensitivity and mostly affect the gastrointestinal tract, such as food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and celiac disease. These reactions can be differentiated by their clinical presentation, severity, age at onset, and natural history. Among non-IgE-mediated allergic reactions to food, allergic proctocolitis is the most frequent. It usually develops in the first year of life and has excellent prognosis. Although it has a benign course, allergic proctocolitis is challenging for health care professionals because it often presents with hematochezia, requiring an accurate differential diagnosis. Knowledge and management of allergic proctocolitis is of paramount importance for medical practice in allergy and immunology. Its diagnosis is based on clinical history followed by elimination diet, especially cow's milk, with subsequent oral food challenge, which may usually be performed at home. Accurate diagnosis is important to avoid unnecessary elimination diets. For this review, PubMed database was searched for recently published literature reviews and studies on the diagnosis and treatment of non- IgE mediated allergies, with a focus on allergic proctocolitis.

Diretriz Latino-americana sobre o Diagnóstico e Tratamento da Alergia Ocular ­ Em nome da Sociedade Latinoamericana de Alergia, Asma e Imunologia (SLAAI) / Latin American Guideline on the Diagnosis and Treatment of Ocular Allergy ­ On behalf of the Latin American Society of Allergy, Asthma and Immunology (SLAAI)

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.

Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.

Hereditary angioedema and Allergic bronchopulmonary aspergillosis: an unexpected association / Angioedema hereditário e Aspergilose broncopulmonar alérgica: uma associação inesperada

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease involving hypersensitivity to the fungi Aspergillus fumigatus which occur in susceptible patient with asthma or cystic fibrosis, also considered a rare disease. We report a case of HAE and ABPA in a single patient. HAE diagnosis was confirmed: C4 = 3 mg/dL, C1INH < 2.8 mg/dL - nephelometry. Former lung function showed elevation RV and RV/FVC, suggesting small airways lung disease. Positive skin prick test to Aspergillus fumigatus (03 mm); total serum IgE level 3,100 IU/mL (nephelometry - BNII Siemens), eosinophilia 11% (528/mm3) and specific A. fumigatus IgG antibodies 6,8 mgA/L (FEIA - fluorenzymeimmunoassay - ThermoFisher) and Chest CT showed mucoid impaction of the bronchi, consistent to current ABPA. Controlling ABPA could prevent and reduce angioedema attacks, and lung structural damage. Early diagnosis and treatment of both diseases should be emphasized to reduce mortality and morbidity

Angioedema hereditário (AEH) é uma doença autossômica dominante; aspergilose broncopulmonar alérgica (ABPA) é uma doença de hipersensibilidade pulmonar relacionada ao esporo de Aspergillus fumigatus, mais suscetível em pacientes com asma e fibrose cística, ambas são consideradas doenças raras. Apresentamos um caso de AEH e ABPA em um paciente. O diagnóstico de AEH foi confirmado com exames laboratoriais: C4 = 3 mg/dL, C1INH < 2,8 mg/dL - nefelometria. Prova de função pulmonar evidenciou aumento de VR e VR/CVF, sugerindo doenças de pequenas vias aéreas. Teste de puntura positivo para A. fumigatus (03 mm); IgE total = 3.100 IU/mL (nefelometria - BNII Siemens), eosinofilia 11% (528/mm3) e IgG específica para A. fumigatus 6,8 mgA/L (FEIA - ThermoFisher), TC de tórax evidenciou impactação mucoide, consistente com ABPA. Controlar ABPA pode prevenir e reduzir as crises de angioedema e os danos ao tecido pulmonar. O diagnóstico precoce de ambas as doenças deve ser enfatizado para reduzir a morbimortalidade.

Utilidad de las pruebas analíticas en el diagnóstico de alergia a las proteínas de la leche de vaca / Usefulness of analytic tests for the diagnosis of cow's milk protein allergy

Introducción. La alergia a las proteínas de la leche de vaca es la alergia alimentaria más frecuente en los niños y para su diagnóstico se emplean historia clínica dirigida y prueba de provocación oral (PPO), el dosaje sérico de inmunoglobulina E específica (sIgE) y pruebas cutáneas de puntura (SPT, por su sigla en inglés). Sin embargo, su utilidad diagnóstica es difícil de establecer en la población local. El objetivo fue evaluar la utilidad de las pruebas para el diagnóstico de alergia a las proteínas de la leche de vaca (PLV) en la población estudiada. Población y métodos. Análisis retrospectivo de datos de pacientes atendidos en la Unidad de Alergia del Hospital Elizalde entre 2015 y 2018. Se evaluaron SPT y sIgE para leche, alfa-lactoalbúmina, beta-lactoglobulina y caseína, seguidos de PPO y se determinó la utilidad diagnóstica para cada prueba, y sus combinaciones. Resultados. Se evaluaron las pruebas de 239 pacientes. La PPO fue hospitalaria en el 54,8 % de los casos, por reexposición domiciliara en el 35,5 % y en el 9,6 % por incorporación de PLV a la madre. La mayor especificidad fue la de SPT con caseína (96,7 %; intervalo de confianza [IC95%]: 90,8-99,3) y la mayor sensibilidad, la de la combinación de SPT y sIgE con los 4 alérgenos (55,3 %; IC95%: 45,7-64,6). Conclusiones. El trabajo estableció la utilidad diagnóstica de las SPT y el sIgE en la población estudiada.

Introduction. Cow's milk protein allergy is the most common food allergy among children. It can be diagnosed based on a guided history taking and using an oral food challenge (OFC), serum specific immunoglobulin E levels (sIgE), and skin prick tests (SPT). However, it is difficult to establish their diagnostic performance in the local population. Our objective was to assess the usefulness of tests used to diagnose cow's milk protein (CMP) allergy in the studied population. Population and methods. Retrospective analysis of data from patients seen at the Unit of Allergy of a tertiary care pediatric hospital between 2015 and 2018. SPT and sIgE tests were done for milk, alpha-lactalbumin, beta-lactoglobulin, and casein, followed by an OFC, and the diagnostic usefulness of each test, as well as their combination, was established. Results. The tests of 239 patients were assessed. OFC was performed at the hospital in 54.8 % of cases, via a rechallenge test at home in 35.5 %, and through CMP intake by the mother in 9.6 %. The highest specificity was observed with the casein SPT (96.7 %; 95 % confidence interval [CI]: 90.8-99.3) and the highest sensitivity, with the 4-allergen SPT and sIgE combination (55.3 %; 95 % CI: 45.7-64.6). Conclusions. The study established the diagnostic usefulness of SPT and sIgE in the studied population.

Clinical characteristics of IgE-mediated cow's milk protein allergy in children / 中华儿科杂志

Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, β lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23，P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.

Acupoint Autohemotherapy Attenuates Atopic Dermatitis Lesions by Regulating Th1/Th2 Balance in DNCB-Induced BALB/c Mice / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses.@*METHODS@#Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice.@*RESULTS@#Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05).@*CONCLUSION@#A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.

Effect of acupuncture and moxibustion on skin barrier function in guinea pigs with eczema of skin damp-heat accumulation / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture and moxibustion on the water content of stratum corneum (WCSC), expression of serum inflammatory factors and aquaporin 3 (AQP3) in skin, lung and rectum in guinea pigs with eczema of skin damp-heat accumulation, and to explore the possible mechanism of acupuncture and moxibustion for regulating skin barrier function.@*METHODS@#A total of 24 male albino guinea pigs were randomly divided into a blank group (n=6) and a modeling group (n=18). The guinea pigs in the modeling group were induced by 2,4-dinitrochlorobenzene (DNCB) to establish the eczema model of skin damp-heat accumulation. The guinea pigs with successful modeling were further randomly divided into a model group, a medication group and an acupuncture-moxibustion group, 6 guinea pigs in each group. The guinea pigs in the medication group were treated with loratadine tablets (0.8 mg/kg) by gavage, once a day for 7 days; the guinea pigs in the acupuncture-moxibustion group were treated with acupuncture at "Feishu" (BL 13), "Pishu" (BL 20), "Quchi" (LI 11), "Zusanli" (ST 36) and "Xuehai" (SP 10); at the same time, moxibustion was applied at "Feishu" (BL 13) and "Zusanli" (ST 36), moxibustion intervention for 10 min and needle retaining for 15 min at each acupoint, once a day for 7 days. The eczema area and severity index (EASI) score was evaluated before and After intervention, and WCSC and trans-epidermal water loss (TEWL) were measured by skin tester. After intervention, The HE staining was used to observe the changes of skin histomorphology in each group; ELISA was used to measure the contents of serum immunoglobulin E (IgE), interleukin (IL)-4 and IL-17; Western blot was used to measure the protein expression of AQP3 in skin, lung and rectum.@*RESULTS@#Before the intervention, compared with the blank group, the EASI scores and TEWL were increased in the remaining groups (P<0.01), and the WCSC was decreased (P<0.01). After the intervention, compared with the model group, the EASI scores and TEWL were decreased (P<0.05, P<0.01), and WCSC was increased (P<0.01) in the medication group and the acupuncture-moxibustion group. The epidermal structure in the blank group was complete and the fibers in the dermis were arranged orderly; in the model group, epidermal hyperkeratosis, proliferation of granular layer, spinous cell layer and basal layer, and disordered arrangement of dermal fibers and infiltration of inflammatory cells were observed. The morphological performance in the medication group and the acupuncture-moxibustion group was better than that in the model group. Compared with the blank group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 and the protein expression of AQP3 in skin, lung and rectum were decreased in the model group (P<0.01, P<0.05). Compared with the model group, the contents of serum IgE and IL-17 were decreased and the contents of serum IL-4 were increased in the medication group and the acupuncture-moxibustion group (P<0.01), and the protein expression of AQP3 in skin, lung and rectum in the acupuncture- moxibustion group were increased (P<0.05). Compared with the medication group, the contents of serum IgE and IL-17 were increased (P<0.01), and the content of serum IL-4 was decreased (P<0.01) in the acupuncture-moxibustion group.@*CONCLUSION@#Acupuncture and moxibustion could improve the epidermal water metabolism and skin tissue morphology in guinea pigs with eczema of skin damp-heat accumulation. Its mechanism may be related to regulating inflammatory factors, up-regulating the expression of AQP3, and then repairing the skin barrier function.

Reatividade cruzada entre betalactâmicos: uma abordagem prática / Cross-reactivity among beta-lactams: a practical approach

Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.

Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.

The role of biologics in eosinophilic esophagitis / O papel dos imunobiológicos na esofagite eosinofílica

Eosinophilic esophagitis (EoE) is a chronic inflammation in the esophageal mucosa driven by an antigen-mediated abnormal immune response with apparent increasing prevalence worldwide. Genetically predisposed individuals present with a dysfunctional esophageal barrier and an abnormal immune response mediated by Th2 and IgE against certain allergens. Consequently, esophageal lesions can cause dysmotility, fibrosis and loss of esophageal barrier function. Clinical manifestations are age-related and include symptoms of esophageal dysfunction. Diagnosis is established by specific histological features associated with the presence of at least 15 eosinophils per high-power field. Management of EoE includes control of allergic diseases with diet restrictions and/or pharmacological treatment with proton-pump inhibitors and corticosteroids, not completely effective and limited by possible side effects and impairment of quality of life. Although immunological mechanisms of EoE are still less clear than other allergic diseases, biologic trials indicate some promising perspectives for EoE management. The purpose of this review is to present the current evidence of biologic drugs as options for EoE treatment.

Esofagite eosinofílica (EOE) é uma inflamação crônica da mucosa esofágica com resposta imune antígeno-mediada anormal e com aparente aumento mundial na prevalência. Indivíduos geneticamente predispostos se apresentam com quadro de disfunção da barreira esofágica e uma resposta imune, mediada por TH2 e IGE, anormal contra certos alérgenos. Consequentemente, lesões esofágicas podem causar dismotilidade, fibrose e perda da função de barreira. O quadro clínico apresenta variação conforme idade e inclui sintomas de disfunção esofágica. O diagnóstico é estabelecido por achados histológicos específicos associados à presença de, ao menos, 15 eosinófilos por campo de alta potência. O manejo inclui controle do quadro alérgico com restrição dietética e/ou tratamento medicamentoso com bloqueadores da bomba de prótons e corticosteroides. São tratamentos sem completa efetividade, com efeitos colaterais e prejuízo na qualidade de vida. Ainda que os mecanismos imunológicos da EOE sejam menos claros que as demais doenças alérgicas, novos ensaios com imunobiológicos salientam uma perspectiva promissora de tratamento para a EOE. O objetivo desta revisão é apresentar as atuais evidências de uso de imunobiológicos como uma nova opção de terapêutica para a esofagite eosinofílica.

Resposta ao dupilumabe na dermatite atópica grave sem uso prévio de imunossupressor sistêmico durante a pandemia de COVID-19 / Response to dupilumab in severe atopic dermatitis without prior use of systemic immunosuppressive agents during the COVID-19 pandemic

A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por intenso prurido e eczema recorrente. Acomete principalmente a infância, mas tem se tornado bastante prevalente em adolescentes e até em adultos. Apesar de ser geralmente não fatal, apresenta uma carga psicossocial importante para os pacientes e seus familiares. O tratamento da DA envolve a hidratação cutânea e medicações anti-inflamatórias. Em casos graves, pode haver necessidade de terapia sistêmica com imunossupressores como ciclosporina, metotrexato e azatioprina. Mais recentemente, alguns imunobiológicos estão em desenvolvimento para controle da DA. O dupilumabe é um anticorpo monoclonal com ação dupla anti-IL-4/IL-13, liberado para tratamento de crianças a partir de 6 anos com DA grave e adolescentes/adultos com DA moderada a grave. O objetivo deste artigo foi relatar uma série de casos de pacientes adolescentes e adultos com DA grave e sua resposta ao dupilumabe durante a pandemia do COVID-19. Trata-se de quatro pacientes (três do sexo feminino), com piora significativa da DA durante o ano de 2020. Todos tinham história de DA desde a infância, com exames complementares evidenciando sensibilização IgE-mediada para ácaros. Já haviam sido submetidos a diversos tratamentos tópicos e sistêmicos, inclusive a cursos de corticosteroides orais. Nenhum deles havia recebido imunossupressor sistêmico, porém estavam recusando este tipo de tratamento devido ao medo da pandemia. Todos apresentaram boa resposta ao dupilumabe, evidenciada pela redução do número de lesões cutâneas e prurido, com poucos efeitos colaterais. Dois pacientes apresentaram sintomas sugestivos de COVID-19 durante o tratamento com dupilumabe (um com confirmação por PCR), com boa evolução. Concluindo, os pacientes com DA grave possuem grande impacto na qualidade de vida e, durante a pandemia de COVID-19, muitos apresentaram piora significativa do seu quadro dermatológico. Nesse contexto, o dupilumabe se mostrou uma opção terapêutica eficaz e segura para tratamento destes pacientes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczema. It mainly affects childhood but has become quite prevalent in adolescents and even adults. Despite being generally nonfatal, it has an important psychosocial burden for patients and their families. AD treatment involves skin hydration and antiinflammatory medications. In severe cases, systemic therapy with immunosuppressive agents such as cyclosporine, methotrexate, and azathioprine may be necessary. More recently, some biologicals are being developed to control AD. Dupilumab is a monoclonal antibody with anti-IL-4/IL-13 dual-action, approved for the treatment of children from 6 years of age with severe AD and adolescents/adults with moderate to severe AD. This article aimed to report a case series of adolescent and adult patients with severe AD and their response to dupilumab during the COVID-19 pandemic. These are four patients (three female), with a significant worsening of AD during the year 2020. All had a history of AD since childhood, with complementary exams showing IgE-mediated sensitization to mites. They had already undergone several topical and systemic treatments, including courses on oral corticosteroids. None of them had received systemic immunosuppressive agents, but they were refusing this type of treatment due to fear of the pandemic. All had a good response to dupilumab, evidenced by a reduction in the number of skin lesions and pruritus, with few side effects. Two patients had symptoms suggestive of COVID-19 during treatment with dupilumab (one confirmed by PCR) with a good outcome. In conclusion, patients with severe AD have a great impact on quality of life and, during the COVID-19 pandemic, many had a significant worsening of their dermatological condition. In this context, dupilumab proved to be an effective and safe therapeutic option for the treatment of these patients.

Omalizumabe no tratamento de urticária solar refratária aos anti-histamínicos: relato de caso e revisão da literatura / Omalizumab in the treatment of solar urticaria refractory to antihistamines: a case report and literature review

A urticária solar é uma forma rara de urticária crônica induzida (UCInd). Os sintomas se iniciam minutos após a exposição ao sol e persistem por até 2 horas, interferindo nas atividades diárias do paciente, e consequentemente na sua qualidade de vida. O omalizumabe, anticorpo monoclonal anti-IgE já aprovado para o tratamento da urticária crônica espontânea, tem sido utilizado no tratamento das urticárias crônicas induzidas com boa resposta, inclusive na urticária solar. Neste artigo, relatamos um caso de urticária solar refratária aos anti-histaminicos, sua evolução após o uso do omalizumabe, e fazemos uma breve revisão da literatura sobre o tema.

Solar urticaria is a rare form of chronic inducible urticaria. Symptoms start minutes after exposure to the sun and persist for up to 2 hours, interfering with the patients' daily activities and, consequently, their quality of life. Omalizumab, a monoclonal anti-IgE antibody already approved for the treatment of chronic spontaneous urticaria, has been used in the treatment of chronic inducible urticaria, including solar urticaria, with good response. In this article, we report a case of solar urticaria refractory to antihistamines, show the patient's evolution after the use of omalizumab, and briefly review the literature on the subject.