CD40 Ligand Deficiency in Latin America: Clinical, Immunological, and Genetic Characteristics.

CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.

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.

Technical performance of a lateral flow immunoassay for detection of anti-SARS-CoV-2 IgG in the outpatient follow-up of non-severe cases and at different times after vaccination: comparison with enzyme and chemiluminescent immunoassays.

This study assessed the technical performance of a rapid lateral flow immunochromatographic assay (LFIA) for the detection of anti-SARS-CoV-2 IgG and compared LFIA results with chemiluminescent immunoassay (CLIA) results and an in-house enzyme immunoassay (EIA). To this end, a total of 216 whole blood or serum samples from three groups were analyzed: the first group was composed of 68 true negative cases corresponding to blood bank donors, healthy young volunteers, and eight pediatric patients diagnosed with other coronavirus infections. The serum samples from these participants were obtained and stored in a pre-COVID-19 period, thus they were not expected to have COVID-19. In the second group of true positive cases, we chose to replace natural cases of COVID-19 by 96 participants who were expected to have produced anti-SARS-CoV-2 IgG antibodies 30-60 days after the vaccine booster dose. The serum samples were collected on the same day that LFIA were tested either by EIA or CLIA. The third study group was composed of 52 participants (12 adults and 40 children) who did or did not have anti-SARS-CoV-2 IgG antibodies due to specific clinical scenarios. The 12 adults had been vaccinated more than seven months before LFIA testing, and the 40 children had non-severe COVID-19 diagnosed using RT-PCR during the acute phase of infection. They were referred for outpatient follow-up and during this period the serum samples were collected and tested by CLIA and LFIA. All tests were performed by the same healthcare operator and there was no variation of LFIA results when tests were performed on finger prick whole blood or serum samples, so that results were grouped for analysis. LFIA's sensitivity in detecting anti-SARS-CoV-2 IgG antibodies was 90%, specificity 97.6%, efficiency 93%, PPV 98.3%, NPV 86.6%, and likelihood ratio for a positive or a negative result were 37.5 and 0.01 respectively. There was a good agreement (Kappa index of 0.677) between LFIA results and serological (EIA or CLIA) results. In conclusion, LFIA analyzed in this study showed a good technical performance and agreement with reference serological assays (EIA or CLIA), therefore it can be recommended for use in the outpatient follow-up of non-severe cases of COVID-19 and to assess anti-SARS-CoV-2 IgG antibody production induced by vaccination and the antibodies decrease over time. However, LFIAs should be confirmed by using reference serological assays whenever possible.

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.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.

RESUMO: Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.

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)

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.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

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.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies / II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias

ABSTRACT In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.

RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.

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.

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.

Allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies: Hospital Israelita Albert Einstein experience.

OBJECTIVE: To report the experience of a tertiary care hospital with allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies. METHODS: Seven pediatric patients with primary immunodeficiencies (severe combined immunodeficiency: n = 2; combined immunodeficiency: n = 1; chronic granulomatous disease: n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1) who underwent eight hematopoietic stem cell transplants in a single center, from 2007 to 2010, were studied. RESULTS: Two patients received transplants from HLA-identical siblings; the other six transplants were done with unrelated donors (bone marrow: n = 1; cord blood: n = 5). All patients had pre-existing infections before hematopoietic stem cell transplants. One patient received only anti-thymocyte globulin prior to transplant, three transplants were done with reduced intensity conditioning regimens and four transplants were done after myeloablative therapy. Two patients were not evaluated for engraftment due to early death. Three patients engrafted, two had primary graft failure and one received a second transplant with posterior engraftment. Two patients died of regimen related toxicity (hepatic sinusoidal obstruction syndrome); one patient died of progressive respiratory failure due to Parainfluenza infection present prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. CONCLUSION: Patients' status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.