Gene mapping strategy for Alu elements rearrangements: Detection of new large deletions in the SERPING1 gene causing hereditary angioedema in Brazilian families.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder mainly caused by mutations in the SERPING1 gene, determining a deficit of C1 inhibitor (C1-INH). In approximately 10% of the cases, HAE with C1-INH deficiency (C1-INH-HAE) is caused by large gene rearrangements, which are not detected by Sanger sequencing. Here we present the exon quantification technique (EQT), a molecular diagnostic test for the detection of large genetic rearrangements in SERPING1, mapping the exact size and location of the deletion caused by the recombination of Alu elements. EQT analysis was performed on total DNA extracted from blood of patients belonging to two Brazilian families with a medical history of HAE, low plasma levels of C4 and C1-INH and no pathogenic alteration in SERPING1 analyzed by Sanger sequencing. RESULTS: Two large deletions were found, one of 1356 pb and one of 1804 pb, which resulted from recombination of two Alu elements present in introns 3 and 4 of the gene. CONCLUSION: These results showed that the EQT could be used as a simple, rapid, and efficient diagnosis test for analysis of large deletions and insertions involving SERPING1, otherwise not detected by Sanger sequencing, serving as a support technique for molecular diagnosis of HAE.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions.

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis.

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Diretrizes brasileiras para o diagnóstico e tratamento do angioedema hereditário ­ 2017 / Brazilian guidelines for the diagnosis and treatment of hereditary angioedema ­ 2017

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises de edema com o envolvimento de múltiplos órgãos. A doença é desconhecida por muitos profissionais da área da saúde e, portanto, subdiagnosticada. Os pacientes que não são diagnosticados e tratados adequadamente têm uma mortalidade estimada de 25% a 40%, devido ao angioedema da laringe, resultando em asfixia. O angioedema de alças intestinais é outra manifestação importante e incapacitante, que pode ser a principal ou a única durante uma crise da doença. Neste cenário, um grupo de especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e do Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) atualizou as diretrizes para o diagnóstico e terapia do angioedema hereditário.

Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40%, due to laryngeal angioedema, which results in asphyxia. Angioedema affecting bowel loops is another important, incapacitating presentation that may be the main or only manifestation during a crisis. In this scenario, a group of experts affiliated with Associação Brasileira de Alergia e Imunologia (ASBAI) and Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) has updated the guidelines for the diagnosis and treatment of hereditary angioedema.

IgE, IgG4 e IgA específicas na alergia ao látex / Specific IgE, IgG4, and IgA in latex allergy

Objetivo: A alergia ao látex é considerada um problema mundial de saúde por estar associada a reações potencialmente fatais. O objetivo principal deste estudo é identificar fatores clínico-laboratoriais associados à sensibilização e alergia ao látex, avaliando as concentrações de IgE, IgG4 e IgA específicas nestas condições. Métodos: Estudo observacional transversal em uma coorte de 400 crianças e adolescentes com defeito do fechamento do tubo neural. Os pacientes realizaram entrevista clínica e foram submetidos a coleta de sangue periférico para a detecção dos níveis séricos de IgE, IgG4 e IgA específicas para látex. As prevalências de sensibilização e alergia ao látex foram calculadas e as variáveis clínico-laboratoriais coletadas foram analisadas. Resultados: A prevalência de sensibilização e de alergia ao látex em pacientes com defeito de fechamento do tubo neural foi de 33,2% e 12,2%, respectivamente. As manifestações clínicas de alergia ao látex mais frequentes foram as cutâneas (79,6%), mas anafilaxia foi observada em 4,75% dos pacientes. Os fatores clínico-cirúrgicos associados à alergia ao látex foram identificados e um escore de sintomas para rastrear os pacientes foi desenvolvido. A concentração de IgE sérica específica para látex ≥ 0,77 kUA/L tem boa acurácia para diferenciar os pacientes sensibilizados assintomáticos dos alérgicos. As dosagens de IgE sérica específica para alérgenos recombinantes também apresentaram boa acurácia no diagnóstico da alergia. Conclusões: Maior concentração de IgE específica para látex e Hevb5, menor concentração de IgG4 específica para látex e escore de sintomas ≥ 40% estiveram associados com alergia ao látex.

Objective: Latex allergy is considered a global health problem because it is associated with life-threatening reactions. The main objective of this study was to identify clinical and laboratory factors associated with sensitization and allergy to latex, assessing the concentrations of latex-specific IgE, IgG4, and IgA. Methods: This was an observational study of a cohort of 400 children and adolescents with neural tube closure defect. Patients underwent a clinical interview and had their blood drawn for the measurement of serum levels of latex-specific IgE, IgG4, and IgA. The prevalence rates of sensitization and allergy to latex were calculated, and clinical and laboratory variables were analyzed. Results: The prevalence rates of sensitization and allergy to latex in patients with neural tube closure defects were 33.2 and 12.2%, respectively. Cutaneous manifestations of latex allergy were the most common ones (79.6%), but anaphylaxis was observed in 4.75% of the patients. Clinical and surgical factors associated with latex allergy were identified, and a symptom scoring system was developed as a screening tool. A latex-specific IgE concentration ≥ 0.77 kUA/L showed good accuracy to differentiate between asymptomatic sensitization and allergy. The measurement of specific IgE to recombinant allergens also showed good accuracy in the diagnosis of allergy. Conclusions: Higher concentrations of latex-specific IgE and Hevb5, lower concentrations of latex-specific IgG4, and a symptom score ≥ 40% were associated with latex allergy.

Uso a longo prazo de alternativas terapêuticas aos anti-inflamatórios não-esteroidais / Long term use of therapeutic alternatives for non-steroidal anti-inflammatory drugs

A benzidamina e o etoricoxibe são drogas que podem ser utilizadas como alternativa terapêutica em pacientes com hipersensibilidade aos anti-inflamatórios não-esteroidais (AINEs). O objetivo do estudo foi avaliar a utilização destas medicações a longo prazo em pacientes com teste de provocação negativo. Métodos: Pacientes com hipersensibilidade aos AINEs que apresentaram teste de provocação negativo foram contactados por telefone e questionados sobre a utilização posterior da drogatestada. Os pacientes que responderam que não voltaram a utilizar a droga foram questionados sobre os motivos pelo qualnão usaram. Resultados: Dos 53 pacientes testados, 50 apresentaram teste de provocação negativo. Destes, 36 foram contactados por telefone e 18 haviam utilizado novamente a droga sem qualquer reação. Dentre os que não foram expostos novamente aos medicamentos, metade não o fez porque não julgou necessário, e a outra metade por receio de uma nova reação. Conclusões: O teste de provocação oral é seguro para a determinação de alternativas terapêuticas, mas a eficácia do mesmo está diretamente relacionada ao entendimento do paciente quanto a possibilidade de novas reações. Além disso, as indicações para o teste também devem ser revistas.

Benzydamine and etoricoxib are drugs that can be used as an alternative therapy in patients with hypersensitivity to thenon-steroidal anti-inflammatory drugs (NSAIDs). The aim of the study was to evaluate the long-term use of these drugs inpatients with a negative drug provocation test. Methods: Patients with NSAIDs hypersensitivity that presented a negative drug provocation test were contacted by telephone and questioned about the subsequent use of the tested drug. The patients who answered that they had not used the drug again were questioned on the reasons for not using it. Results: Of the 53 patients tested, 50 presented a negative drug provocation test. Of these, 36 were contacted by telephone and 18 had used the drug again without any reaction. Among the ones that were not exposed again to the drugs, halfof them had not used because they didn't judge necessary, andt he other half were afraid of a new reaction. Conclusions: The drug provocation test is safe for the determination of an alternative therapy, but the effectiveness oft he test is directly related to the patient's understanding about the possibility of new reactions. Besides, the indications for the test should also be reviewed.

Reações de hipersensibilidade à insulina / Insulin hypersensitivity reactions

As reações de hipersensibilidade à insulina têm diminuído significativamente após a introdução da preparação de insulina humana. No entanto, alguns casos continuam sendo observados na prática clínica. Revisamos os principais aspectos relacionados à fisiopatologia, às manifestações clínicas, ao diagnóstico e ao tratamento das reações de hipersensibilidade a insulina. As reações à insulina podem estar relacionadas a qualquerum dos quatro mecanismos de Gell e Coombs. As manifestações clínicas surgem geralmente nas quatro primeiras semanas de tratamento e incluem mais frequentemente reações locais, mas também urticária, angioedema e anafilaxia. A sensibilização à insulina pode ser avaliada pelo teste cutâneo de leitura imediata, pesquisa de IgE sérica específica, teste intradérmico e pesquisa de IgG específica. O tratamento envolve o uso deadrenalina, anti-histamínicos e corticosteróides, dependendo do tipo e gravidade da reação. Em alguns casos a dessensibilização deve ser considerada.

Hypersensitivity reactions to the insulin have been decreesing significantly after the introduction of the preparation of human insulin. However, some cases continue being observed in clinical practice. We revised the main aspects related to the physiopathology, clinical manifestations, diagnosis and treatmentof the insulin hypersensitivity reactions. Insulin reactions can be related with any one of the four mechanisms of Gell and Coombs. Clinical manifestations usually appear in the first 4 weeks of treatment and they more frequently include local reactions, but also urticaria, angioedema and anaphylaxis. Insulin sensitization can be evaluated by the prick test, serum specific IgE, intradermal test and serum specific IgG.

Reações adversas aos antiinflamatórios não esteroidais / Adverse reactions to nonsteroidal anti-inflammatory

Objetivo: rever as principais reações adversas aos antiinflamatórios não esteroidais (AINEs) publicadas nos últimos dez anos. Fontes dos dados: artigos originais indexados nos bancos de dados Medline e LILACS de janeiro de 1998 a dezembro de 2007, e livros textos selecionados. Síntese dos dados: esta revisão enfocou: classificação, mecanismos. de ação, principais manifestações clínicas, tratamento e dessensibilização à aspirina.Conclusões: os AINEs são drogas amplamente usadas, por outro lado apresentam alta prevalência entre as reações adversas a drogas, as quais veem aumentando nos últimos anos. História clínica bem elaborada é a chave do diagnóstico. O diagnóstico pode ser estabelecido pela prova de provocação com ácido acetilsalicílico. As reações adversas aos AINEs podem ser fatais. As reações adversas devem ser notificadas para que se estabeleça o perfil de segurança desses medicamentos.

Objective: to review the main adverse reactions to nons 8 years. Data base: original papers indexed on Medline and LILACS data bases from january of 1998 to december of 2007 and select books. Data synthesis: this review focuses on: classification, action mechanisms, clinical manifestations, treatment and aspirin desensitization. Conclusion: NSAIO are widely used nevertheless they have a high prevalence of drug reactions which is increasing in recent last years. A good clinical history is the key to diagnosis. The gold standard to diagnosis is the aspirin challenge. Adver se reactions to NSAIO may be fatal. The adverse reactions to drugs should be notified to establish the drug safety profile.

Alergia à penicilina: conduta alergológica / Penicillin allergy: practice parameters

Objetivo: O objetivo do Grupo de Estudos de Alergia a Drogas da ASBAI é apresentar um projeto operacional diagnóstico, acoplado a uma estratégia de conduta alergológica, que auxilie o profissional da área da saúde no Brasil a conduzir adequadamente o paciente que possa ser alérgico à penicilina, em conformidade com os atuais parâmetros da literatura médica internacional. Métodos: O diagnóstico de alergia à penicilina é muitas vezes exagerado de maneira inapropriada, sem que haja uma adequada documentação imunológica. Muitos indivíduos são incorretamente rotulados de alérgicos e os antibióticos betalactâmicos passam, infelizmente, a ser evitados pelo resto da vida. Torna-se, portanto, necessária a correlação entre a história clínica apresentada e a investigação alergoimunológica padronizada. Resultados: Cerca de 95 das moléculas de penicilina se combinam a proteínas, e o determinante antigênico benzil peniciloil formado é então denominado de determinante maior ou principal da penicilina, responsável por urticária e/ou angioedema. Além deste determinante maior, outros componentes menores ou secundários da penicilina são formados e podem induzir respostas IgE-mediadas. Estes determinantes menores são importantes, participando dos graves quadros anafiláticos. A mistura dos determinantes menores consiste em: benzil penicilina, benzil peniciloato (hidrólise alcalina) e benzil peniloato (hidrólise ácida). Conclusões: Os testes alérgicos cutâneos para detecção de alergia à penicilina estão indicados quando houver história clínica de suspeição, doença grave requerendo a sua utilização em paciente com história sugestiva de alergia específica, e quando não houver antibióticos alternativos. Nesta última situação e quando os testes alérgicos padronizados forem positivos recomenda-se a dessensibilização cuidadosa e controlada.