Managing moderate-to-severe paediatric asthma: a scoping review of the efficacy and safety of fluticasone propionate/salmeterol.

BACKGROUND: Fluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting ß2-agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled with ICS monotherapy plus as-needed short-acting ß2-agonists, or already adequately controlled with ICS/LABA. OBJECTIVE: Compared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children. ELIGIBILITY CRITERIA: A literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma. SOURCES OF EVIDENCE: The Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors. CHARTING METHODS: Selected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed. RESULTS: Improvements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids. CONCLUSIONS: FP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population.

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.

IgE-mediated cow's milk allergy in Brazilian children: Outcomes of oral food challenge.

Background: Oral food challenge (OFC) is useful for diagnosing food allergies and assessing tolerance, but severe reactions may occur during the procedure. Objective: To characterize the frequency and severity of reactions during cow's milk (CM) OFCs. Methods: A cross-sectional study was conducted to analyze the outcome of cow's milk oral food challenges (CMOFCs) performed to confirm IgE-mediated CM allergy or to assess food tolerance. CM was given first as baked milk (BM), followed by whole CM if there was no prior reaction to BM. An OFC was considered positive if IgE-mediated symptoms developed up to 2 h after ingestion. Symptoms were described and variables including age at OFC, prior anaphylaxis, other atopic diseases, and skin test results were compared according to the OFC outcomes. Results: A total of 266 CMOFCs were performed, including 159 patients with a median age of 6.3 years old. One hundred thirty-six tests were positive and 62 resulted in anaphylaxis. Thirty-nine anaphylactic reactions were observed up to 30 min after the first dose. Severe anaphylaxis (cardiovascular and/or neurological involvement) was reported in 5 tests. A second dose of epinephrine was required in 3 tests, and 1 presented a biphasic response. Younger patients had a higher risk of anaphylaxis during baked milk oral food challenge (BMOFC) (p = 0.009). The frequency of anaphylaxis was higher in patients submitted to BM (p = 0.009). Conclusions: Anaphylaxis is a known complication of CMOFCs even when there is no prior anaphylaxis or when conducted with baked products. This study reinforces the importance of conducting OFC in appropriate settings with a well-trained team.

Anafilaxia durante o primeiro ano de vida em pacientes com alergia à proteína do leite de vaca / Anaphylaxis during the first year of life of infants with cow's milk protein allergy

Objetivo: Descrever as manifestações de anafilaxia precoce em lactentes com alergia à proteína do leite de vaca (APLV) e descrever as condutas terapêuticas utilizadas. Método: Estudo observacional transversal retrospectivo que analisou pacientes com APLV atendidos no Instituto da Criança e do Adolescente do Hospital das Clínicas da FMUSP, entre 1990-2015, que apresentaram sintomas de alergia no primeiro ano de vida, com diagnóstico de anafilaxia, comparados a pacientes alérgicos sem anafilaxia desencadeada por ingestão de leite de vaca. Os pacientes foram caracterizados de maneira epidemiológica, tipo de sintoma apresentado e tratamento realizado. Os dados foram analisados no programa estatístico GraphPad Software Inc. Para avaliar a associação entre categorias, foi utilizado o Teste Exato de Fisher, e para comparações entre grupos, o Teste de Mann Whitney. Os resultados de p < 0,05 foram considerados significativos. Resultados: De um total de 120 crianças avaliadas (68 M:52 F), 85 (70,83%) lactentes preencheram os critérios da World Allergy Organization (WAO) para anafilaxia. As manifestações de alergia IgE mediada foram prioritariamente cutâneas [102 (85%)]. Nos pacientes com diagnóstico de anafilaxia, as principais manifestações foram urticária [39 (45,8%)], vômito [36 (42,3%)] e dispneia [19 (22,3%)]. A recorrência do episódio de anafilaxia ocorreu em 41 (34,16%) pacientes. A adrenalina (45%) e o anti-histamínico (63,3%) foram os medicamentos mais utilizados. Observa-se também que 6 (7%) pacientes com diagnóstico de anafilaxia não receberam nenhum tratamento. Conclusão: Anafilaxia no primeiro ano de idade apresenta quadro clínico semelhante aos pacientes mais velhos, mas ainda há elevada taxa de recorrência de episódios e subtratamento. Mais estratégias de educação precisam ser desenvolvidas.

Objective: To describe the early manifestations of anaphylaxis in infants with cow's milk protein allergy (CMPA) and the therapeutic approach. Method: In this cross-sectional observational study, we retrospectively reviewed the medical records of patients with CMPA treated at the Institute for Children and Adolescents of Hospital das Clínicas, University of São Paulo Medical School, from 1990 to 2015. Patients who developed allergic symptoms during the first year of life and had a diagnosis of anaphylaxis were compared with allergic patients without anaphylaxis triggered by cow's milk. Patients were characterized according to epidemiological features, type of symptoms, and treatment received. Data were analyzed using GraphPad software. Associations between categories were assessed by Fisher's exact test, and groups were compared by the Mann-Whitney test. Results with p<0.05 were considered statistically significant. Results: Of 120 infants evaluated (68 male: 52 female), 85 (70.83%) met the World Allergy Organization criteria for anaphylaxis. Most infants had cutaneous manifestations of immunoglobulin E (IgE)-mediated allergy (n=102, 85%). In those with a diagnosis of anaphylaxis, the main manifestations were urticaria (n=39, 45.8%), vomiting (n=36, 42.3%), and dyspnea (n=19, 22.3%). Anaphylaxis recurred in 41 patients (34.16%). Epinephrine (45%) and antihistamines (63.3%) were the most used drugs. Six patients (7%) with a diagnosis of anaphylaxis received no treatment. Conclusion: Anaphylaxis during the first year of life showed clinical features similar to those of older pediatric patients, but the rates of episode recurrence and undertreatment are still high. More education strategies need to be developed.

Idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma

Abstract Objective: To evaluate idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma and healthy controls. Methods: Cross-sectional study was conducted on 150 asthmatic adolescents and 300 controls. Adolescents completed a self-administered questionnaire regarding painful symptoms, use of electronic devices, and physical activity. Seven musculoskeletal pain syndromes were evaluated, and Asthma Control Test (ACT) was assessed. Results: Musculoskeletal pain (42% vs. 61%, p = 0.0002) and musculoskeletal pain syndromes (2.7% vs. 15.7%, p = 0.0006) were significantly lower in asthmatic adolescents than in controls. The frequency of pain in the hands and wrists was reduced in asthmatic than in controls (12.6% vs. 31.1%, p = 0.004), in addition to cell phone use (80% vs. 93%, p < 0.0001), simultaneous use of at least two electronic media (47% vs. 91%, p < 0.0001), myofascial syndrome (0% vs. 7.1%, p = 0.043), and tendinitis (0% vs. 9.2%, p = 0.008). Logistic regression analysis, including asthma with musculoskeletal pain as the dependent variable, and female sex, ACT > 20, simultaneous use of at least two electronic devices, cell phone use, and weekends and weekdays of cell phone use, as independent variables, showed that female sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.929-6.316; p = 0.0009) and ACT ≥ 20 (OR, 0.194; 95% CI, 0.039-0.967; p = 0.045) were associated with asthma and musculoskeletal pain (Nagelkerke R2 = 0.206). Conclusion: Musculoskeletal pain and musculoskeletal pain syndromes were lower in adolescents with asthma. Female sex was associated with musculoskeletal pain in asthmatic, whereas patients with asthma symptoms and well-controlled disease reported a lower prevalence of musculoskeletal pain.

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.

Idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma.

OBJECTIVE: To evaluate idiopathic musculoskeletal pain, musculoskeletal pain syndromes, and use of electronic devices in adolescents with asthma and healthy controls. METHODS: Cross-sectional study was conducted on 150 asthmatic adolescents and 300 controls. Adolescents completed a self-administered questionnaire regarding painful symptoms, use of electronic devices, and physical activity. Seven musculoskeletal pain syndromes were evaluated, and Asthma Control Test (ACT) was assessed. RESULTS: Musculoskeletal pain (42% vs. 61%, p = 0.0002) and musculoskeletal pain syndromes (2.7% vs. 15.7%, p = 0.0006) were significantly lower in asthmatic adolescents than in controls. The frequency of pain in the hands and wrists was reduced in asthmatic than in controls (12.6% vs. 31.1%, p = 0.004), in addition to cell phone use (80% vs. 93%, p < 0.0001), simultaneous use of at least two electronic media (47% vs. 91%, p < 0.0001), myofascial syndrome (0% vs. 7.1%, p = 0.043), and tendinitis (0% vs. 9.2%, p = 0.008). Logistic regression analysis, including asthma with musculoskeletal pain as the dependent variable, and female sex, ACT > 20, simultaneous use of at least two electronic devices, cell phone use, and weekends and weekdays of cell phone use, as independent variables, showed that female sex (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.929-6.316; p = 0.0009) and ACT ≥ 20 (OR, 0.194; 95% CI, 0.039-0.967; p = 0.045) were associated with asthma and musculoskeletal pain (Nagelkerke R2 = 0.206). CONCLUSIONS: Musculoskeletal pain and musculoskeletal pain syndromes were lower in adolescents with asthma. Female sex was associated with musculoskeletal pain in asthmatic, whereas patients with asthma symptoms and well-controlled disease reported a lower prevalence of musculoskeletal pain.

Microbiological profile in chronic granulomatous disease patients in a single Brazilian primary immunodeficiencies center

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency. Infections of the lungs, skin, lymph nodes, and liver are the hallmark of CGD with frequent initial manifestations of the disease. The aim of the present study was to describe the sites of infections and their causative agents in 38 CGD pediatric patients. Methods: This was a retrospective single-center cohort study comprising CGD patients, and followed for over last 40 years at the Allergy and Immunology Unit of a tertiary hospital in São Paulo, Brazil. Sites of infections and their causative agents were described. Results: A total of 38 patients were included (36 males and 2 females). Median age at the onset of symptoms was 45 days (7 days–7 years) and that at the time of diagnosis was 23 months (1 month–12 years); 31.6% of the parents reported death of relatives during childhood and 21% (8 cases) had another male family member with CDG. The most common infections were pneumonia (81.6%), skin infections (50.0%), adenitis (42.1%), and liver abscess (23.7%). In all, 188 cultures were positive (85.6% for bacteria and 14.4% for fungi). The most prevalent bacterial agents were Staphylococcus sp. (12.4%), Staphylococcus aureus (11.2%), and Klebsiella pneumoniae (9.3%). Aspergillus sp. and Candida sp. were 56% and 22.2% of the isolated fungi, respectively. Mycobacterium tuberculosis was isolated in 5.6% and Mycobacterium bovis in 0.9% (only in 1 patient) of cultures. Conclusion: Staphylococcus sp., Staphylococcus aureus, and Aspergillus sp. were the most frequent agents in this cohort. M. tuberculosis should be considered in endemic areas. Detection of infectious agents drives to find adequate treatment and benefits the evolution of patients with CGD (AU)

Microbiological profile in chronic granulomatous disease patients in a single Brazilian primary immunodeficiency center

Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency. Infections of lung, skin, lymph nodes, and liver are the hallmark of CGD and frequently the initial manifestation of the disease. The aim of the present paper is to describe the sites of infections and their causative agents in 38 pediatric patients with CGD Methods This retrospective, single-center cohort study included CGD patients followed at the allergy and immunology unit of a tertiary hospital in São Paulo, Brazil over the last 40 years. Sites of infections and their causative agents were described. Results Thirty-eight patients were included (36 males). The median age of onset of symptoms was 45 days (ranging from 7 days–7 years), and the median age at diagnosis was 23 months (ranging from 1 month–12 years). In all, 31.6% of the patients reported a family history of child deaths and 21% (eight cases) had another male family member with CGD. The most common infections were pneumonia (81.6%), skin infections (50.0%), adenitis (42.1%), and liver abscess (23.7%); 188 cultures were positive (85.6% bacteria; 14.4% fungi). The most prevalent bacterial agents were Staphylococcus sp. (12.4%), Staphylococcus aureus (11.2%), and Klebsiella pneumoniae (9.3%). Aspergillus sp. and Candida sp. were 56% and 22.2% of the isolated fungi, respectively. Mycobacterium tuberculosis was isolated in 5.6% and Mycobacterium bovis in one patient (0.9%). Conclusion Staphylococcus sp., Staphylococcus aureus, and Aspergillus sp. were the most frequent agents found in this cohort. M. tuberculosis should be considered in endemic area. Detection of infectious agents drives to the adequate treatment and benefits the evolution of patients with CGD (AU)

Microbiological profile in chronic granulomatous disease patients in a single Brazilian primary immunodeficiency center.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency. Infections of lung, skin, lymph nodes, and liver are the hallmark of CGD and frequently the initial manifestation of the disease. The aim of the present paper is to describe the sites of infections and their causative agents in 38 pediatric patients with CGD. METHODS: This retrospective, single-center cohort study included CGD patients followed at the allergy and immunology unit of a tertiary hospital in São Paulo, Brazil over the last 40 years. Sites of infections and their causative agents were described. RESULTS: Thirty-eight patients were included (36 males). The median age of onset of symptoms was 45 days (ranging from 7 days-7 years), and the median age at diagnosis was 23 months (ranging from 1 month-12 years). In all, 31.6% of the patients reported a family history of child deaths and 21% (eight cases) had another male family member with CGD. The most common infections were pneumonia (81.6%), skin infections (50.0%), adenitis (42.1%), and liver abscess (23.7%); 188 cultures were positive (85.6% bacteria; 14.4% fungi). The most prevalent bacterial agents were Staphylococcus sp. (12.4%), Staphylococcus aureus (11.2%), and Klebsiella pneumoniae (9.3%). Aspergillus sp. and Candida sp. were 56% and 22.2% of the isolated fungi, respectively. Mycobacterium tuberculosis was isolated in 5.6% and Mycobacterium bovis in one patient (0.9%). CONCLUSION: Staphylococcus sp., Staphylococcus aureus, and Aspergillus sp. were the most frequent agents found in this cohort. M. tuberculosis should be considered in endemic area. Detection of infectious agents drives to the adequate treatment and benefits the evolution of patients with CGD.

Transfusion-related acute lung injury associated to intravenous immunoglobulin infusion in a pediatric patient.

Case report of a patient with an immunodeficiency who demands regular replacement of intravenous immunoglobulin. She presented an episode of transfusion-related acute lung injury shortly after using an immunoglobulin product different than the one she usually received. The patient evolved with respiratory changes (hypoxia, dyspnea, change in pulmonary auscultation) minutes after the end of the infusion, and received non-invasive respiratory support. She was discharged after 36 hours with good outcome. The patient achieved full recovery, showing no further reactions in subsequent immunoglobulin infusions (no longer receiving the product that was used when she had the episode of transfusion-related acute lung injury). Although rare, this reaction is potentially serious and has no specific treatment other than supportive therapy. The literature is scarce regarding the risk of recurrence. The decision on whether to proceed with immunoglobulin therapy after this adverse effect should be analyzed individually, assessing the possible risks and benefits for the patient.

Safety of yellow fever vaccine administration in confirmed egg-allergic patients.

Yellow fever vaccine (YFV) is recommended in endemic areas but represents a risk for egg-allergic patients, as it is cultivated in embryonated eggs. This study aims to describe the outcomes of yellow fever vaccination in patients with confirmed egg allergy (EA). Methods:A prospective study was conducted from January 2018 to September 2019. EA was diagnosed through positive oral food challenge (OFC), recent history of anaphylaxis following egg contact (anaphylaxis in the last 6 months) or immediate allergic reaction in the last 2 months with positive specific IgE. A skinprick test (SPT) with YFV was performed. If the SPT was negative, an intradermal test (ID) was performed at a 1:100 dilution. If the ID was negative, a full dose of YFV was administered. If the skin prick test or ID were positive, the YFV was administered using a graded dosing protocol. Results: It was included 58 patients with confirmed egg allergy (36 M:22F), with a median age of 2.3 years (0.7-13.9 y/o). Forty-two patients had a positive OFC. Nine reported recent anaphylaxis. The other 7 had reactions in the last 2 months with positive specific IgE. During OFC, 15 presented anaphylaxis, while the other 27 presented hives and/or angioedema or vomiting. SPT with YFV was negative in all patients. ID was negative in 48 patients who uneventfully received a full dose of YFV. Ten patients had a positive ID and received YFV in graded doses. Six patients presented a mild reaction controlled with antihistamines, and 4 patients received the vaccine without reactions. Positive ID was significantly related to the vaccine reaction (p < 0.0001). Administration of YFV using a specific protocol was safe even in anaphylactic patients. However, we recommend performing the ID, which can help predict a higher risk of vaccine reaction. An appropriate setting is required to control adverse events.

Transfusion-related acute lung injury associated to intravenous immunoglobulin infusion in a pediatric patient / Lesão pulmonar aguda relacionada à transfusão associada com infusão de imunoglobulina intravenosa em paciente pediátrico

ABSTRACT Case report of a patient with an immunodeficiency who demands regular replacement of intravenous immunoglobulin. She presented an episode of transfusion-related acute lung injury shortly after using an immunoglobulin product different than the one she usually received. The patient evolved with respiratory changes (hypoxia, dyspnea, change in pulmonary auscultation) minutes after the end of the infusion, and received non-invasive respiratory support. She was discharged after 36 hours with good outcome. The patient achieved full recovery, showing no further reactions in subsequent immunoglobulin infusions (no longer receiving the product that was used when she had the episode of transfusion-related acute lung injury). Although rare, this reaction is potentially serious and has no specific treatment other than supportive therapy. The literature is scarce regarding the risk of recurrence. The decision on whether to proceed with immunoglobulin therapy after this adverse effect should be analyzed individually, assessing the possible risks and benefits for the patient.

RESUMO Relato de caso de paciente com imunodeficiência que necessitava de reposição regular de imunoglobulina endovenosa. Ela apresentou um episódio de lesão pulmonar aguda relacionada à transfusão após uso de produto de imunoglobulina diferente daquele que recebia habitualmente. Evoluiu com alterações respiratórias (hipóxia, dispneia e alteração de ausculta pulmonar) minutos após o fim da infusão, necessitando de suporte respiratório não invasivo. A paciente recebeu alta hospitalar após 36 horas, com boa evolução. Obteve recuperação total dos sintomas, sem mais reações nas infusões subsequentes de imunoglobulina (sendo optado por não mais prescrever o produto que foi usado quando ocorreu o episódio de lesão pulmonar aguda relacionada à transfusão). Apesar de rara, essa reação é potencialmente grave, não possui tratamento específico além de terapia de suporte, e há pouca informação na literatura sobre o risco de recorrência. A decisão sobre o seguimento da terapia com imunoglobulina após esse efeito adverso deve ser analisada individualmente, avaliando os possíveis riscos e benefícios para o paciente.

Segurança da vacina de febre amarela em pacientes comprovadamente alérgicos à proteína do ovo / Safety of yellow fever vaccine in egg allergic patients

Introdução: A vacina de febre amarela, recomendada em áreas endêmicas, é contraindicada em alérgicos à proteína do ovo (APO) por ser cultivada em ovos de galinha embrionados. Objetivo: O objetivo do estudo foi mostrar a segurança da vacina de febre amarela em pacientes comprovadamente APO. Método: Foi realizado estudo prospectivo em hospital quaternário, no período de janeiro a outubro de 2018. Foram incluídos pacientes com APO confirmada por teste de provocação oral (TPO), reação anafilática à proteína do ovo nos últimos 6 meses, ou reação de APO nos últimos 2 meses associada à IgE específica positiva. Todos foram submetidos ao teste de puntura com a vacina na apresentação pura. Se negativo, realizado teste intradérmico (ID) com a vacina na diluição de 1:100. Se ID negativo, vacina aplicada em dose plena. Se teste de puntura ou ID positivo, vacina aplicada fracionada segundo protocolo de dessensibilização. Resultados: Dos 78 pacientes com história presumida de APO, confirmou-se o diagnóstico em 43 (30M:13F, mediana idade 2,7 a): 30 por TPO, 7 com anafilaxia em menos de 6 meses da vacina, e 6 com reação imediata após ingestão do ovo há menos de 2 meses e IgE específica positiva. Durante o TPO, 12 apresentaram anafilaxia, e os demais (18) apresentaram urticária e/ou angioedema ou vômitos. Todos os testes de puntura (43) foram negativos. ID foi negativo em 37 pacientes, que receberam a dose plena da vacina, sem reações. Apenas 6 apresentaram ID positivo e necessitaram dessensibilização para vacina. Metade desses pacientes (3/6) apresentou reações de hipersensibilidade leves e foi tratada com anti-H1 e/ou corticoide oral. O ID positivo foi significativamente relacionado à reação à vacina (p = 0,0016). Conclusão: Concluiuse ser possível vacinar alérgicos a ovo, com um protocolo seguro, mesmo em paciente comprovadamente anafilático. É necessária uma unidade especializada para sua realização, com capacidade de controlar possíveis situações de risco.

Introduction: The yellow fever vaccine (YFV) is recommended in endemic areas, but represents a risk for egg allergic (EA) patients, as it is cultivated in chicken embryos. Objective: This study aimed to describe the outcomes of YFV in patients with confirmed egg allergy. Methods: A prospective study was conducted in a quaternary hospital, from January to October 2018. EA was diagnosed through oral food challenge (OFC) or recent history of anaphylaxis following egg contact in the past 6 months or allergic reaction in the past 2 months with positive specific immunoglobulin E (IgE). Skin prick testing (SPT) with YFV was performed in all participants. If SPT was negative, an intradermal test (IDT) was performed at 1:100 dilution. If IDT was negative, a full dose of YFV was administered. If SPT was positive, the YFV was administered using a graded-dose protocol. Results: Among 78 patients with prior history of EA, 43 were confirmed (30 male to 13 female, median age of 2.7 years). Thirty patients had a positive OFC, seven reported recent anaphylaxis, and six had reactions in the past 2 months with positive specific IgE. During OFC, 12 patients had anaphylaxis and 18 had urticaria and/or angioedema or vomiting. SPT with YFV was negative in all patients (43). IDT was negative in 37 patients, who received a full dose of YFV, uneventfully. Six patients had a positive IDT and received the YFV in graded doses; half of them had a mild reaction controlled with antihistamines and three patients received the vaccine without reactions. Positive IDT was significantly related to vaccine reaction (p=0.0016). Conclusion: The YFV using a specific protocol was safe even in anaphylactic patients. An appropriate setting is required in order to control possible adverse events.

Esofagite eosinofílica: um conceito em evolução? / Eosinophilic esophagitis: an evolving concept?

O objetivo deste artigo é revisar a literatura dos últimos 10 anos sobre esofagite eosinofílica (EoE) e descrever os conceitos atuais da doença em seus aspectos de definição, fisiopatologia, fatores de risco, quadro clínico, diagnóstico e tratamento. Foram pesquisados artigos na base de dados do PubMed, do Bireme/ LILACS e do SciELO, nos últimos 10 anos. Os critérios para a inclusão dos artigos foram: (a) publicação nos últimos 10 anos, (b) artigos originais, (c) apenas humanos, (d) artigos de revisão, (e) diretrizes. Os critérios de exclusão foram: (a) artigos que não continham como tema principal a EoE, (b) artigos repetidos, (c) descrição de casos, (d) artigos com abordagem muito específicas para tratamento e diagnóstico. Foi realizada leitura dos resumos por dois pesquisadores, e posterior seleção dos artigos completos para a leitura. Foram acrescentados estudos que aprofundavam aspectos cruciais da revisão, sendo incluídos, ao todo, 3 consensos, 35 estudos e 3 artigos de revisão, que constituíram o total de artigos analisados. A conclusão é de que a EoE é uma doença crônica, cujos aspectos clínicos são fundamentais para a suspeita diagnóstica, mas requer a associação de achados endoscópicos e histológicos para sua confirmação. Na última década, houve modificações significativas nos critérios diagnósticos e algumas novas recomendações no tratamento, mas que necessitam uma observação em longo prazo.

The objective of this paper was to review literature on eosinophilic esophagitis (EoE) published over the last 10 years and to describe current disease concepts related to definition, pathophysiology, risk factors, clinical presentation, diagnosis and treatment. We searched the PubMed, Bireme/LILACS and SciELO databases for articles published in the last 10 years. The following inclusion criteria were used to select articles: (a) publication in the last 10 years; (b) original articles; (c) studies with humans only; (d) review articles; (e) guidelines. Exclusion criteria were: (a) articles that did not have EoE as the main subject; (b) repeated articles; (c) case reports; (d) articles addressing a very specific treatment or diagnostic technique. Abstracts were screened by two investigators, and articles meeting the criteria were selected for full-text reading. Any relevant studies addressing crucial aspects of the review were added to the sample, resulting in a total of 3 consensus articles, 35 original articles, and 3 review articles. The review showed that EoE is a chronic disease in which clinical aspects are essential for diagnostic suspicion, but associated endoscopic and histological findings are required to confirm diagnosis. Over the last 10 years, significant changes were observed in diagnostic criteria, and some new treatment recommendations emerged, however still requiring long-term follow-up.

Primary hypogammaglobulinemia: The impact of early diagnosis in lung complications.

OBJECTIVE:: To describe clinical features, tomographic findings and pulmonary function in pediatric patients with primary hypogammaglobulinemia (PH). METHOD:: A retrospective cohort study of children with PH who received intravenous immunoglobulin (IVIG) and prophylactic antibiotics between 2005 and 2010. Epidemiological and clinical features, computed tomography (CT) findings, and spirometric data were compared, assuming a 5% significance level. RESULTS:: We evaluated 30 patients with PH. After the start of IVIG replacement, there was a decline in the frequency of pneumonia (p<0.001). The 11 patients with bronchiectasis in their first CT scan were older at diagnosis (p=0.001) and had greater diagnostic delay (p=0.001) compared to patients without bronchiectasis. At the end of the study, 18 patients had bronchiectasis and 27 also had other lung disorders, alone or in combination. The Bhalla score was applied to the last CT scan of 16 patients, with a median score of 11 (range 7-21), with a positive correlation between the score and the number of pneumonias after the start of treatment (r=0.561; p=0.024). The score was also correlated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values in 13/16 patients, with negative correlation to FEV1 previously to bronchodilator (r=-0.778; p=0.002) and after bronchodilator (r =-0.837; p<0.001) and FVC (r=-0.773; p=0.002). CONCLUSION:: Pulmonary complications were common in this cohort, despite the decrease in the frequency of pneumonia with treatment. Early investigation of patients with recurrent infections for primary immunodeficiencies can reduce the frequency of these complications. The monitoring of changes in spirometry may indicate the need to carry out radiological investigation.

Cow's milk allergy: Evaluating tolerance through skin-prick test.

OBJECTIVE:: To evaluate the wheal diameter in allergy skin-prick tests (SPT) with cow's milk extract (CM) comparing tolerant and persistent patients. METHOD:: A retrospective cohort study involving database analysis of children with diagnosis of cow's milk protein allergy (CMPA) mediated by immunoglobulin E in a specialized outpatient clinic that regularly performed SPT between January 2000 and July 2015. Patients were allocated into two groups: tolerant or persistent. Comparisons were made at diagnosis and over time between tolerant and persistent patients using Fisher's, Mann-Whitney or Wilcoxon tests and significance level at 5%. RESULTS:: After applying inclusion and exclusion criteria, the sample includes 44 patients (29 tolerant and 15 who persisted with CMPA). In the tolerant group, the medians of SPT were: 6 mm at diagnosis and 2 mm at the development of tolerance; a significant difference (p<0.0001) was found. In the persistent group, the median SPT at diagnosis was 7 mm, while in the last SPT it was 5 mm, with no statistical difference (p=0.173). The comparison of medians in the last SPT between groups was significant (p=0.001), with a reduction greater than 50% in SPT in the tolerant group. CONCLUSION:: Serial SPTs were useful for diagnosis, and a decrease higher than 50% in diameter can indicate the moment to perform oral food challenge (OFC) tests, helping to detect tolerance in CMPA.

Primary hypogammaglobulinemia: The impact of early diagnosis in lung complications / Hipogamaglobulinemia primária: o impacto do diagnóstico precoce nas complicações pulmonares

Summary Objective: To describe clinical features, tomographic findings and pulmonary function in pediatric patients with primary hypogammaglobulinemia (PH). Method: A retrospective cohort study of children with PH who received intravenous immunoglobulin (IVIG) and prophylactic antibiotics between 2005 and 2010. Epidemiological and clinical features, computed tomography (CT) findings, and spirometric data were compared, assuming a 5% significance level. Results: We evaluated 30 patients with PH. After the start of IVIG replacement, there was a decline in the frequency of pneumonia (p<0.001). The 11 patients with bronchiectasis in their first CT scan were older at diagnosis (p=0.001) and had greater diagnostic delay (p=0.001) compared to patients without bronchiectasis. At the end of the study, 18 patients had bronchiectasis and 27 also had other lung disorders, alone or in combination. The Bhalla score was applied to the last CT scan of 16 patients, with a median score of 11 (range 7-21), with a positive correlation between the score and the number of pneumonias after the start of treatment (r=0.561; p=0.024). The score was also correlated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values in 13/16 patients, with negative correlation to FEV1 previously to bronchodilator (r=-0.778; p=0.002) and after bronchodilator (r =-0.837; p<0.001) and FVC (r=-0.773; p=0.002). Conclusion: Pulmonary complications were common in this cohort, despite the decrease in the frequency of pneumonia with treatment. Early investigation of patients with recurrent infections for primary immunodeficiencies can reduce the frequency of these complications. The monitoring of changes in spirometry may indicate the need to carry out radiological investigation.

Resumo Objetivo: descrever características clínicas, tomográficas e de função pulmonar em pacientes pediátricos com hipogamaglobulinemia primária (HP). Método: estudo de coorte retrospectivo de crianças com HP que recebiam gamaglobulina endovenosa (GEV) e antibiótico profilático entre 2005 e 2010. As características epidemiológicas, clínicas, os achados de tomografia e espirometria foram comparadas adotando níveis de significância de 5%. Resultados: foram avaliados 30 pacientes com HP. Após o início da reposição de GEV, houve redução da frequência de pneumonias (p<0,001). Os 11 pacientes que apresentavam bronquiectasias na primeira tomografia computadorizada (TC) eram mais velhos ao diagnóstico (p=0,001) e tiveram maior atraso no diagnóstico (p=0,001) quando comparados aos pacientes sem bronquiectasias. Ao final do estudo, 18 pacientes apresentavam bronquiectasias e 27/30 também apresentaram outras alterações pulmonares, isoladas ou concomitantes. O escore de Bhalla foi aplicado à última TC de 16/30 pacientes, com mediana do escore de 11 (variação 7-21), com correlação positiva entre o escore e o número de pneumonias após o início do tratamento (r=0,561; p=0,024). O escore foi ainda correlacionado com valores de volume expiratório forçado no primeiro segundo (VEF1) e capacidade vital forçada (CVF) obtidos por espirometria de 13/16 pacientes, com correlação negativa com VEF1 pré- (r=-0,778; p=0,002) e pós-broncodilatador (r=-0,837; p<0,001) e CVF (r=-0,773; p=0,002). Conclusão: complicações pulmonares foram frequentes nesta coorte, apesar da diminuição na frequência de pneumonias com o tratamento. A investigação precoce de pacientes com infecções de repetição para imunodeficiências primárias pode reduzir a frequência dessas complicações. A monitorização de alterações na espirometria pode indicar a necessidade de investigação radiológica.

Cow's milk allergy: Evaluating tolerance through skin-prick test / Alergia ao leite de vaca: avaliação da tolerância pelo teste cutâneo alérgico

Summary Objective: To evaluate the wheal diameter in allergy skin-prick tests (SPT) with cow’s milk extract (CM) comparing tolerant and persistent patients. Method: A retrospective cohort study involving database analysis of children with diagnosis of cow’s milk protein allergy (CMPA) mediated by immunoglobulin E in a specialized outpatient clinic that regularly performed SPT between January 2000 and July 2015. Patients were allocated into two groups: tolerant or persistent. Comparisons were made at diagnosis and over time between tolerant and persistent patients using Fisher’s, Mann-Whitney or Wilcoxon tests and significance level at 5%. Results: After applying inclusion and exclusion criteria, the sample includes 44 patients (29 tolerant and 15 who persisted with CMPA). In the tolerant group, the medians of SPT were: 6 mm at diagnosis and 2 mm at the development of tolerance; a significant difference (p<0.0001) was found. In the persistent group, the median SPT at diagnosis was 7 mm, while in the last SPT it was 5 mm, with no statistical difference (p=0.173). The comparison of medians in the last SPT between groups was significant (p=0.001), with a reduction greater than 50% in SPT in the tolerant group. Conclusion: Serial SPTs were useful for diagnosis, and a decrease higher than 50% in diameter can indicate the moment to perform oral food challenge (OFC) tests, helping to detect tolerance in CMPA.

Resumo Objetivo: avaliar o diâmetro da pápula do teste cutâneo alérgico (TCA) com extrato de leite de vaca (LV) comparando pacientes tolerantes e persistentes. Método: estudo de coorte retrospectivo de análise de banco de dados de crianças com diagnóstico de alergia à proteína do leite de vaca (APLV) mediada pela imunoglobulina E, em ambulatório especializado, que realizaram TCA de forma evolutiva, sendo alocados em dois grupos: tolerantes ou persistentes, entre janeiro de 2000 e julho de 2015. As comparações foram realizadas ao diagnóstico e evolutivamente entre tolerantes e persistentes, pelos testes de Fisher, Mann-Whitney ou Wilcoxon, utilizando níveis de significância de 5%. Resultados: aplicando critérios de inclusão e exclusão, a amostra incluiu 44 pacientes (29 tolerantes e 15 que persistiram com APLV). No grupo tolerante, as medianas do TCA foram: ao diagnóstico, de 6 mm, e, no desenvolvimento de tolerância, de 2 mm, com diferença significante (p<0,0001). No grupo persistente, a mediana do TCA ao diagnóstico foi de 7 mm e no momento do último TCA, de 5 mm, sem diferença estatística (p=0,173). A comparação das medianas no último TCA entre os grupos mostrou-se significante (p=0,001), com redução maior de 50% no valor do TCA no grupo tolerante. Conclusão: os TCA seriados foram úteis para o diagnóstico, e a redução maior que 50% em seu diâmetro pode indicar o momento para realização de testes de provocação oral (TPO), auxiliando na detecção de tolerância na APLV.

Perceptions of caregivers of patients with cow's milk allergy regarding the treatment / Percepção dos familiares de pacientes com alergia ao leite de vaca em relação ao tratamento

The aim of this qualitative study was to understand the perceptions of caregivers of children and adolescents with cow's milk allergy regarding the disease and its treatment. Nine caregivers were interviewed and content analysis method was used. Three categories with subcategories emerged: treatment and education of the patient and their caregivers (life experiences, bases of treatment, coping with the disease), resolution of the disease (hope, gradual improvement), quality of life (social inclusion, family daily activities, costs of dietary treatment). Caregivers experienced difficulties during the initial treatment but pointed out that the guidance given during follow-up made the adjustments easier. Family members commented on the difficulties about lack of cooperation from other family members regarding the restrictive diet, their experience coping with the allergic reaction, doubts about the treatment and gaps on knowledge about the disease by other physicians and people. Some of them believed that there is no treatment for the disease, because there are no drugs or vaccines, but they were waiting for cure. The majority of relatives were satisfied with the gradual improvement of patients observed by reduction on the severity of symptoms and tolerance of milk traces within foods. In addition, they commented on the efforts to give a normal life for their children, the changes in their daily lives and the difficulty to buy special products. Concluding, caregivers of children and adolescents with cow's milk allergy feel a great burden of the disease.(AU)

Este estudo qualitativo teve como objetivo compreender as percepções de familiares de crianças e adolescentes com alergia à proteína do leite de vaca (APLV) em relação à doença e seu tratamento. Foram realizadas nove entrevistas e foi utilizado o método de análise de conteúdo. Surgiram três categorias com subcategorias: tratamento e educação do paciente e familiares (experiências vividas, base do tratamento e como lidar com a doença), resolução da doença (expectativa e melhora gradativa), qualidade de vida (inclusão social, cotidiano familiar e custo dos alimentos). Os familiares vivenciaram dificuldades durante o início do tratamento, mas revelaram que as orientações fornecidas no seguimento tornaram as adaptações à doença mais fáceis. Comentaram sobre as dificuldades em obter a colaboração de outros membros da família em relação à dieta de exclusão, suas experiências frente a uma reação alérgica, dúvidas quanto ao tratamento e lacunas do conhecimento sobre a doença entre outros médicos e na população em geral. Alguns deles acreditavam que não havia tratamento para a APLV, porque não existiam medicamentos ou vacinas, mas mantinham a esperança da descoberta de uma cura. A maioria dos familiares estava satisfeita com a melhora gradativa dos seus filhos, percebida pela redução da gravidade dos sintomas e tolerância a traços de leite. Também comentaram sobre os esforços em proporcionar uma vida normal para seus filhos, as mudanças em suas vidas e a dificuldade em comprar alimentos especiais. Em conclusão, os familiares de crianças e adolescentes com APLV sentem grande impacto da doença.(AU)