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2.
Arq. Asma, Alerg. Imunol ; 6(2): 151-169, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400194

ABSTRACT

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises recorrentes de edema que acometem o tecido subcutâneo e o submucoso, com envolvimento de diversos órgãos. Os principais locais afetados são face, membros superiores e inferiores, as alças intestinais e as vias respiratórias superiores. Em decorrência da falta de conhecimento dessa condição por profissionais de saúde, ocorre atraso importante no seu diagnóstico, comprometendo a qualidade de vida dos indivíduos afetados. Além disso, o retardo no diagnóstico pode resultar em aumento da mortalidade por asfixia devido ao edema de laringe. A natureza errática das crises com variação do quadro clínico e gravidade dos sintomas entre diferentes pacientes, e no mesmo paciente ao longo da vida, se constitui em desafio no cuidado dos doentes que têm angioedema hereditário. O principal tipo de angioedema hereditário é resultante de mais de 700 variantes patogênicas do gene SERPING1 com deficiência funcional ou quantitativa da proteína inibidor de C1, porém nos últimos anos outras mutações foram descritas em seis outros genes. Ocorreram avanços importantes na fisiopatologia da doença e novas drogas para o tratamento do angioedema hereditário foram desenvolvidas. Nesse contexto, o Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) em conjunto com a Associação Brasileira de Alergia e Imunologia (ASBAI) atualizou as diretrizes brasileiras do angioedema hereditário. O maior conhecimento dos diversos aspectos resultou na divisão das diretrizes em duas partes, sendo nessa primeira parte abordados a definição, a classificação e o diagnóstico.


Hereditary angioedema is an autosomal dominant disease characterized by recurrent attacks of edema that affect the subcutaneous tissue and the submucosa, involving several organs. The main affected sites are the face, upper and lower limbs, gastrointestinal tract, and upper airways. Because health professionals lack knowledge about this condition, there is a significant delay in diagnosis, compromising the quality of life of affected individuals. Furthermore, delayed diagnosis may result in increased mortality from asphyxia due to laryngeal edema. The erratic nature of the attacks with variations in clinical course and severity of symptoms among different patients and in one patient throughout life constitutes a challenge in the care of patients with hereditary angioedema. The main type of hereditary angioedema results from more than 700 pathogenic variants of the SERPING1 gene with functional or quantitative deficiency of the C1 inhibitor protein, but in recent years other mutations have been described in six other genes. Important advances have been made in the pathophysiology of the disease, and new drugs for the treatment of hereditary angioedema have been developed. In this context, the Brazilian Study Group on Hereditary Angioedema (GEBRAEH) in conjunction with the Brazilian Association of Allergy and Immunology (ASBAI) updated the Brazilian guidelines on hereditary angioedema. Greater knowledge of different aspects resulted in the division of the guidelines into two parts, with definition, classification, and diagnosis being addressed in this first part.


Subject(s)
Humans , Therapeutics , Classification , Diagnosis , Angioedemas, Hereditary , Quality of Life , Asphyxia , Signs and Symptoms , Societies, Medical , Pharmaceutical Preparations , Glycoproteins , Laryngeal Edema , Allergy and Immunology , Mutation
3.
Arq. Asma, Alerg. Imunol ; 6(2): 170-196, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400199

ABSTRACT

O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.


The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients in Brazil.


Subject(s)
Humans , Drug Therapy , Angioedemas, Hereditary , Antibodies, Monoclonal, Humanized , Bradykinin Receptor Antagonists , Patients , Quality of Life , Therapeutics , Bradykinin , Pharmaceutical Preparations , Kallikreins , Reference Drugs
4.
Arq. Asma, Alerg. Imunol ; 6(2): 214-224, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400202

ABSTRACT

A urticária aguda é uma causa frequente de consulta com alergistas, caracterizada por urticas e/ou angioedema. Embora autolimitada e benigna, pode causar desconforto significativo e raramente representar uma doença sistêmica grave ou reação alérgica com risco de vida. Nesta revisão, elaborada pelo Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia, foram abordadas as principais questões referentes ao tema para auxiliar o médico especialista e generalista.


Acute urticaria is a frequent cause of consultations with allergists, being characterized by wheals and/or angioedema. Although self-limited and benign, it may cause significant discomfort and uncommonly represent a serious systemic disease or life-threatening allergic reaction. In this review prepared by the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology, the main questions about this topic are addressed to help specialists and general practitioners.


Subject(s)
Humans , Urticaria , Epinephrine , Milk Hypersensitivity , Egg Hypersensitivity , Drug Hypersensitivity , Shellfish Hypersensitivity , Nut and Peanut Hypersensitivity , Histamine H1 Antagonists , Anaphylaxis , Spider Bites , Physicians , Societies, Medical , Therapeutics , Anti-Inflammatory Agents, Non-Steroidal , Sweet Syndrome , Dermatitis, Allergic Contact , Adrenal Cortex Hormones , Hypereosinophilic Syndrome , Schnitzler Syndrome , Mastocytosis, Cutaneous , Diagnosis , Allergy and Immunology , Erythema , Angioedemas, Hereditary , Food Hypersensitivity , Allergists , Hypersensitivity , Angioedema
6.
Arq. Asma, Alerg. Imunol ; 6(1): 141-143, jan.mar.2022.
Article in English | LILACS | ID: biblio-1400124

ABSTRACT

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


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


Subject(s)
Humans , Male , Child , Aspergillosis, Allergic Bronchopulmonary , Angioedemas, Hereditary , Patients , Association , Asthma , Therapeutics , Immunoglobulin E , Rare Diseases , Early Diagnosis , Diagnosis , Eosinophilia
7.
Article in Chinese | WPRIM | ID: wpr-953296

ABSTRACT

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.


Subject(s)
Angioedemas, Hereditary/genetics , Asian People , Female , Humans , Male , Mutation , Pedigree , Retrospective Studies
8.
Medicina (B.Aires) ; 81(4): 645-648, ago. 2021. graf
Article in English | LILACS | ID: biblio-1346519

ABSTRACT

Abstract Hereditary angioedema (HAE) is a rare disease with an autosomal dominant heredity pattern, due to mutations in the gene encoding the C1 esterase inhibitor. The onset of symptoms usually occurs during childhood. Clinically, it is characterized by repeated episodes of angioedema that may affect the skin, abdomen and larynx/pharynx. The occurrence of attacks and their severity are unpredictable and can be fatal without the appropriate treatment. We present the case of an asymptomatic 65-year-old woman, with a history of three adult children diagnosed with HAE. Despite the high probabilities of being a carrier of the mutation, she had not been previously studied. Diagnosis of HAE in a family member would require screening of all at-risk relatives. Early diagnosis is essential to establish a correct and timely therapeutic strategy in order to reduce the morbidity and mortality associated with the disease.


Resumen El angioedema hereditario (HAE) es una enfermedad rara, con un patrón de herencia autosómico dominante, debida a mutaciones en el gen que codifica el inhibidor de la C1 esterasa. El inicio de los síntomas suele ocurrir durante la infancia. Clínicamente se caracteriza por episodios recurrentes de angioedema que pueden afectar la piel, el abdomen y la laringe/faringe. La ocurrencia de los ataques y su gravedad son imprevisibles, y puede resultar fatal sin el tratamiento apropiado. Presentamos el caso de una mujer de 65 años de edad, asintomática, con antecedente de tres hijos adultos con diagnóstico de HAE, quién pese a la alta probabilidad de ser portadora de la mutación, no había sido estudiada previamente. El diagnóstico de HAE en un integrante de la familia obligaría a realizar estudios de cribado en todos los familiares en riesgo. El diagnóstico temprano resulta fundamental para establecer una estrategia terapéutica correcta y oportuna, disminuyendo así la morbimortalidad asociada a la enfermedad.


Subject(s)
Humans , Female , Aged , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/genetics , Angioedema , Family , Complement C1 Inhibitor Protein , Mutation
9.
Arq. Asma, Alerg. Imunol ; 5(2): 208-210, abr.jun.2021. ilus
Article in Portuguese | LILACS | ID: biblio-1398934

ABSTRACT

O angioedema hereditário por défice de C1-inibidor é uma doença rara autossômica dominante com uma prevalência estimada em 1:50.000. Habitualmente a história familiar aponta para este diagnóstico. No entanto, a apresentação atípica com história familiar negativa pode atrasar o diagnóstico de meses a anos. Os autores apresentam o caso de uma criança de 6 anos sem antecedentes pessoais ou familiares relevantes que recorreu ao Serviço de Urgência pediátrico por edema, calor e rubor do cotovelo, joelho e maléolos direitos com 12h de evolução, sem fatores associados. Ao exame objetivo: edema do cotovelo, joelho e maléolos direitos, exantema não pruriginoso maleolar homolateral com discreto desconforto à palpação. Sem elevação dos parâmetros infeciosos ou inflamatórios. Foi iniciada corticoterapia sistêmica, com melhoria lenta do quadro. Teve alta, referenciada à consulta de Imunoalergologia. Na anamnese foram apurados quatro episódios de edema periarticular nos doze meses prévios. A avaliação analítica da criança revelou C1 inibidor 62 mg/dL, C1 inibidor funcional 29%, confirmada em duas determinações, e a dos pais e dos dois irmãos foi normal. No estudo genético não foram identificadas mutações nos genes SERPING. O angioedema hereditário por défice de função do C1-inibidor - tipo II - representa 15 a 20% dos casos. Embora a história familiar seja o maior sinal de alerta para o diagnóstico desta patologia, em 20-25% dos casos ocorre mutação espontânea. Nestes casos um elevado grau de suspeição é necessário e um atraso no diagnóstico pode levar a consequências graves. As opções terapêuticas em crianças menores de 12 anos são ainda limitadas.


Hereditary angioedema with C1-inhibitor deficiency is a rare autosomal dominant disease with an estimated prevalence of 1:50 000. Usually, family history points to this diagnosis. However, atypical presentation with negative family history may delay diagnosis in months to years. The authors describe the case of a 6-year-old girl with apparently no significant family or past medical history, presenting to the emergency department for edema, warmth, and redness of the right elbow, knee, and ankle, which started 12 hours earlier, without associated factors. On physical examination, edema of the right elbow, knee, and ankle, and nonpruritic rash on the right ankle with a slight discomfort on palpation were found. Laboratory infection or inflammation markers were not elevated. Systemic corticosteroids were started, with slow improvement. She was discharged and referred to an immunoallergology outpatient clinic. On medical history taking, four episodes of periarticular edema in the past 12 months were identified. Laboratory evaluation revealed C1-inhibitor at 62 mg/dL and functional C1-inhibitor at 29%, confirmed in two samples; the parents and two siblings were normal. On genetic testing, there were no mutations on the SERPING genes. Hereditary angioedema with C1-inhibitor deficiency ­ ie, type II ­ accounts for 15 to 20% of cases. Even though family history is the major indicator for diagnosis of this condition, a de novo mutation occurs in 20 to 25% of cases. In these cases, a high suspicion is necessary, and a delayed diagnosis could have severe implications. Therapeutic options in children under the age of 12 are limited.


Subject(s)
Humans , Female , Child , Tranexamic Acid , Genetic Testing , Ibuprofen , Adrenal Cortex Hormones , Elbow , Angioedemas, Hereditary , Genes , Knee , Ankle , Mutation , Physical Examination , Therapeutics , Rare Diseases , Diagnosis , Edema , Allergy and Immunology , Delayed Diagnosis , Inflammation
10.
J. pediatr. (Rio J.) ; 97(supl.1): 10-16, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1250226

ABSTRACT

Abstract Objectives: To describe the hereditary angioedema to improve awareness of this condition and reduce diagnostic delay. Data sources: Relevant articles in the MEDLINE database through PubMed. Data synthesis: Hereditary angioedema is rare and has an autosomal dominant pattern of inheritance. Its onset occurs mainly in childhood, but there is an important delay in the diagnosis. In the most frequent phenotype, there is a quantitative and/or functional deficiency in the C1esterase inhibitor protein, which regulates the activation of the complement, contact and fibrinolysis systems with greater formation of bradykinin, the main mediator of angioedema. There is a third type, the hereditary angioedema with a normal C1 inhibitor level, which is rare in children. Clinical manifestations are characterized by recurrent angioedema attacks, mainly in the extremities, abdomen and upper airways, which can progress to asphyxia and death. The main triggers are mechanical trauma, infections and stress. The diagnosis is attained by patient clinical picture and decreased serum levels of C4 and C1esterase inhibitor or its function. In hereditary angioedema with a normal C1 inhibitor, there is no change in these parameters, thus requiring a genetic study. Treatment is based on the use of attack medications and long and short-term prophylaxis. Conclusions: Hereditary angioedema is little known by pediatricians due to the significant delay in diagnosis of this condition, whose onset usually begins in childhood. The presence of recurrent angioedema that does not respond to treatment with antihistamines, corticosteroids and adrenaline should increase the diagnostic suspicion.


Subject(s)
Humans , Child , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/genetics , Angioedema , Bradykinin , Delayed Diagnosis , Pediatricians
11.
Arq. Asma, Alerg. Imunol ; 5(1): 15-18, jan.mar.2021. ilus
Article in Portuguese | LILACS | ID: biblio-1398161

ABSTRACT

No curso da pandemia da COVID-19, o desenvolvimento rápido de vacinas seguras e eficazes é a principal estratégia de saúde pública para conter a propagação da doença. Nesse contexto, esclarecimentos em relação à prioridade e segurança da vacinação contra COVID-19 em pacientes portadores de angioedema hereditário (AEH), assim como de outras doenças, são necessários. Todos os pacientes devem receber a vacina seguindo a estratégia do Ministério da Saúde e manter as medidas de higiene, uso de máscaras e distanciamento social até o controle da pandemia.


During the COVID-19 pandemic, the rapid development of safe and effective vaccines is the main public health strategy to avoid the spread of the disease. In this context, clarifications regarding the priority and safety of vaccination against COVID-19 in patients with hereditary angioedema (HAE), as well as other diseases, are needed. All patients should receive the vaccine according to the Brazilian Ministry of Health strategy and adhere to measures such as maintaining general hygienic measures, wearing masks, and keeping social distance until the pandemic is controlled.


Subject(s)
Humans , Angioedemas, Hereditary , COVID-19 Vaccines , SARS-CoV-2 , COVID-19 , BNT162 Vaccine , 2019-nCoV Vaccine mRNA-1273 , ChAdOx1 nCoV-19 , Patients , Hygiene , Health Strategies , Physical Distancing , Masks
12.
Einstein (Säo Paulo) ; 19: eRW5498, 2021. tab, graf
Article in English | LILACS | ID: biblio-1286289

ABSTRACT

ABSTRACT Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.


RESUMO As crises de angioedema são causas comuns de atendimentos nas emergências, e devido ao potencial de gravidade, é importante que os profissionais que atuam nesses serviços conheçam suas causas e abordagem. Os mecanismos envolvidos no angioedema sem urticas podem ser histaminérgicos ou mediados por bradicinina. As causas mais comuns de angioedema mediado por histamina são alimentos, medicamentos, ferroada de insetos e idiopática. Quando o mediador é a bradicinina, os desencadeantes são os inibidores da enzima conversora de angiotensina e fatores relacionados ao angioedema adquirido com deficiência do inibidor de C1 ou angioedema hereditário que são menos comuns, mas muito importantes pela possibilidade de desfecho fatal. O angioedema hereditário é uma doença rara, caracterizada por crises de edema que acometem o tecido subcutâneo e mucosas de vários órgãos, manifestando-se principalmente por crises de angioedema e dor abdominal. Esse tipo de angioedema não responde ao tratamento usual com adrenalina, anti-histamínicos e corticosteroides. Assim, se não identificados e tratados adequadamente, esses pacientes têm risco de morte por edema de laringe estimado em 25% a 40%. O tratamento do angioedema hereditário mudou drasticamente nos últimos anos, com o desenvolvimento de novos e eficientes fármacos para as crises: inibidor de C1 derivado de plasma, inibidor de C1 recombinante humano, antagonista do receptor B2 da bradicinina (icatibanto) e o inibidor da calicreína (ecalantide). No Brasil, até o momento, estão liberados para uso o inibidor de C1 derivado de plasma e o icatibanto. O manejo correto desses pacientes na emergência evita cirurgias desnecessárias e, principalmente, desfechos fatais.


Subject(s)
Humans , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/drug therapy , Angioedema/diagnosis , Angioedema/drug therapy , Brazil , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Emergency Service, Hospital
13.
Arq. Asma, Alerg. Imunol ; 4(4): 382-393, out.dez.2020. ilus
Article in Spanish | LILACS | ID: biblio-1382033

ABSTRACT

El angioedema hereditario (AEH) es una enfermedad genética rara, con una prevalencia aproximada entre 1 por cada 50.000 habitantes, caracterizada por episodios de edemas a nivel subcutáneo y de mucosas (abdominal, genitourinario, respiratoria), siendo potencialmente mortal cuando hay afectación de la laringe. En Perú se estiman 600 pacientes con AEH. El AEH se puede clasificar del siguiente modo: con deficiencia del inhibidor de C1 (tipos I y II), y sin deficiencia del inhibidor de C1 (denominado anteriormente tipo III). El diagnóstico de laboratorio incluye prueba de complemento C4, prueba cuantitativa y cualitativa para inhibidor de C1 esterasa, y estudios genéticos.


Hereditary angioedema (HAE) is a genetic rare disease with a prevalence of approximately 1 per 50,000 inhabitants, characterized by episodes of edema at the subcutaneous level and mucous membranes (abdominal, genitourinary, respiratory), being potentially fatal when there is involvement of the larynx. In Peru, there are an estimated 600 patients with HAE. HAE can be classified as follows: with C1 inhibitor deficiency (types I and II), and without C1 inhibitor deficiency (previously called type III). Laboratory diagnosis includes C4 complement test, quantitative and qualitative tests for C1 inhibitor esterase, and genetic studies. In this first part of the Clinical Practice Guide, we present the recommendations for the diagnostic approach of HAE.


Subject(s)
Humans , Peru , Mass Screening , Clinical Laboratory Techniques , Diagnosis , Angioedemas, Hereditary , Societies, Medical , Edema
14.
Arq. Asma, Alerg. Imunol ; 4(4): 394-414, out.dez.2020. ilus
Article in Spanish | LILACS | ID: biblio-1382034

ABSTRACT

El angioedema hereditario (AEH) es una enfermedad genética rara, con una prevalencia aproximada entre 1 por cada 50.000 habitantes, caracterizada por episodios de edemas a nivel subcutáneo y de mucosas (abdominal, genitourinario, respiratoria), siendo potencialmente mortal cuando hay afectación de la laringe. En Perú se estiman 600 pacientes con AEH. El AEH se puede clasificar del siguiente modo: con deficiencia del inhibidor de C1 (tipos I y II), y sin deficiencia del inhibidor de C1 (denominado anteriormente tipo III). El diagnóstico de laboratorio incluye prueba de complemento C4, prueba cuantitativa y cualitativa para inhibidor de C1 esterasa, y estudios genéticos. Existen tratamientos específicos a nivel mundial para crisis agudas y profilaxis en AEH. Sin embargo, en Perú el único tratamiento registrado actualmente es el ecallantide, útil en crisis agudas; además, podemos utilizar tratamientos alternativos como el ácido tranexámico y el danazol. En esta segunda parte de la Guía de Práctica Clínica, presentamos las recomendaciones para el manejo y el tratamiento del AEH.


Hereditary angioedema (HAE) is a genetic rare disease with a prevalence of approximately 1 per 50,000 inhabitants, characterized by episodes of edema at the subcutaneous level and mucous membranes (abdominal, genitourinary, respiratory), being potentially fatal when there is involvement of the larynx. In Peru, there are an estimated 600 patients with HAE. HAE can be classified as follows: with C1 inhibitor deficiency (types I and II), and without C1 inhibitor deficiency (previously called type III). Laboratory diagnosis includes C4 complement test, quantitative and qualitative test for C1 inhibitor esterase, and genetic studies. There are specific treatments worldwide for acute crises and prophylaxis in HAE; in Peru the only currently registered treatment is ecallantide, useful in acute crises; we can also use alternative treatments such as tranexamic acid and danazol. In this second part of the Clinical Practice Guide, we present the recommendations for the management and treatment of HAE.


Subject(s)
Humans , Societies, Medical , Therapeutics , Tranexamic Acid , Mass Screening , Angioedemas, Hereditary , Patients , Peru , Complement C4 , Clinical Laboratory Techniques , Diagnosis , Edema , Genetics , Mucous Membrane
15.
Rev. bras. ginecol. obstet ; 42(12): 845-848, Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1156068

ABSTRACT

Abstract Objective To verify the efficacy of short-term prophylaxis for vaginal or cesarean section childbirth with plasma-derived C1-inhibitor concentrate in pregnant women. They should have hereditary angioedema (HAE) and normal plasma C1-inhibitor. Methods Case report of pregnant women diagnosed with HAE with normal C1- inhibitor who had been treated with intravenous C1-inhibitor concentrate for prophylaxis of angioedema attacks when hospitalized for delivery. The exon 9 of the Factor 12 (F12) genotyping gene was performed by automatic sequencing in all patients. Results Three cases of pregnant women with HAE with normal serum level of C1- inhibitor are reported. The genetic test detected the presence of a pathogenic mutation in the F12 gene. Deliveries occurred uneventfully and patients had no HAE symptoms in the following 72 hours. Conclusion C1-inhibitor concentrate could be useful to prevent angioedema attacks during and after delivery.


Resumo Objetivo Verificar a eficácia da profilaxia de curto prazo para o parto vaginal ou cesáreo com inibidor de C1 derivado de plasma concentrado em mulheres grávidas. Eles devem ter angioedema hereditário e inibidor normal de C1 no plasma. Métodos Relato de caso de gestantes diagnosticadas com angioedema hereditário com inibidor de C1 normal que foram tratadas com inibidor intravenoso de concentrado de C1 para profilaxia de ataques de angioedema quando hospitalizadas para o parto. O exon 9 do gene de genotipagem do fator 12 (F12) foi realizado por sequenciamento automático em todos os pacientes. Resultados Três casos de gestantes com angioedema hereditário com nível sérico normal de inibidor de C1 são relatados. O teste genético detectou a presença de uma mutação patogênica no gene F12. Os partos ocorreram sem intercorrências e as pacientes não apresentaram sintomas hereditários de angioedema nas 72 horas seguintes. Conclusão O concentrado de inibidor de C1 pode ser útil para prevenir ataques de angioedema durante e após o parto.


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Pregnancy Complications/diagnosis , Prenatal Diagnosis , Factor XII/genetics , Angioedemas, Hereditary/diagnosis , Pedigree , Cesarean Section , Diagnosis, Differential
16.
Arq. Asma, Alerg. Imunol ; 4(3): 360-362, jul.set.2020. ilus
Article in English | LILACS | ID: biblio-1382011

ABSTRACT

Ecallantide is a specific treatment currently indicated for acute crisis of hereditary angioedema (HAE) due to C1-inhibitor deficiency. Our objective is to report the first administration of ecallantide (Kalbitor®) in Peru, where the treatment was used in an HAE patient with normal C1-inhibitor and no F12 gene alteration. We report the case of a 32-year-old postpartum patient with HAE with normal C1-inhibitor who belongs to the Peruvian Association of Patients with Hereditary Angioedema. During pregnancy, she had increased frequency and intensity of abdominal pain and facial edema crisis and received maintenance treatment with tranexamic acid and spasmolytics, with moderate response. One month postpartum, the patient showed respiratory symptoms and tested positive for coronavirus disease (COVID-19) in a polymerase chain reaction (PCR) test, without any HAE crisis during the infectious process. Three months postpartum, she had an acute laryngeal edema crisis with difficulty breathing and speaking, nausea, and vomiting, triggered by nonsteroidal anti-inflammatory drugs (NSAIDs). The patient then received treatment with antihistamines, corticosteroids, and adrenaline, without improvement; for that reason, the allergist administered ecallantide (Kalbitor®) with good response within the first 15 minutes of administration. Some Peruvian HAE patients have developed mild-to-moderate facial and peripheral edema crisis after NSAID intake, without improvement after administration of allergy treatment. In our patient, HAE crisis was not triggered by COVID-19. The patient showed worsening HAE crisis during pregnancy. The first administration of ecallantide (Kalbitor®) in Peru had good response and tolerance to the treatment as shown in this report.


Ecallantide é um tratamento específico totalmente indicado na crise aguda de deficiência de inibidor de C1 HAE. Nosso objetivo é relatar a primeira administração de Ecallantide (Kalbitor®) no Peru, um caso de paciente peruano com EH com inibidor C1 normal sem alteração genética F12. Relatamos o caso de uma paciente de 32 anos, pós-parto, com HAE inibidor de C1 normal, pertencente à Associação Peruana de Angioedema Hereditário de Pacientes. Durante a gravidez, a paciente apresentou aumento na frequência e intensidade das crises de edema abdominal e facial e recebeu tratamento de manutenção com ácido tranexâmico e espasmolítico, com resposta moderada. Um mês após o parto, a paciente apresentou quadro respiratório e teste de PCR molecular positivo para Doença do Coronavírus (COVID-19), sem crise de AEH durante o processo infeccioso. Três meses após o parto, a paciente apresentou crise de edema agudo de laringe com dificuldade para respirar e falar, náuseas e vômitos, desencadeado por AINH. A paciente recebeu tratamento com anti-histamínicos, corticosteroides e adrenalina sem melhora, por isso o alergista administrou Ecallantide (Kalbitor®) com boa resposta nos primeiros 15 minutos após o início da administração. Alguns pacientes peruanos com AEH desenvolveram crises de edema facial e periférico leve a moderado após a ingestão de AINEs, sem melhora após a administração de tratamento para alergia. Em nossa paciente, a crise de AEH não foi desencadeada por infecção aguda por COVID-19. A paciente apresentou agravamento da crise de AEH durante a gravidez. Apresentamos a primeira administração de Ecallantide (Kalbitor®) no Peru, com boa resposta e tolerância ao tratamento.


Subject(s)
Humans , Female , Adult , Tranexamic Acid , Abdominal Pain , Laryngeal Edema , Postpartum Period , Angioedemas, Hereditary , COVID-19 , Histamine Antagonists , Patients , Peru , Therapeutics , Vomiting , Anti-Inflammatory Agents, Non-Steroidal , Adrenal Cortex Hormones , Edema , Hypersensitivity , Nausea
18.
Rev. bras. anestesiol ; 70(1): 48-50, Jan.-Feb. 2020.
Article in English, Portuguese | LILACS | ID: biblio-1137132

ABSTRACT

Abstract Hereditary angioedema is an autosomal dominant disorder, presenting as sudden and recurring episodes of variable severity of subcutaneous and mucosa edema that may occur spontaneously or in response to triggers. There are three knwon types of hereditary angioedema. The disorder is caused by decrease in the plasma level or change in the functional capacity of C1 inhibitor, with increase in bradykinin and in vascular permeability, and consequent edema. Several measures are required in the perioperative period in order to avoid an acute attack. Prophylaxis should be carried out throughout pregnancy before any surgical procedure, before dental procedures, upon airway handling, on patients with previous episodes of angioedema, and when there are significant changes in volemia. The literature is scarce in regard to the association between hereditary angioedema and pregnancy. We describe a successful case of a pregnant patient with type I hereditary angioedema submitted to a C-section.


Resumo O angioedema hereditário é uma doença autossômica dominante, que se manifesta por crises súbitas, recorrentes e de gravidade variável de edema subcutâneo e submucoso, que podem ocorrer espontaneamente ou em resposta a gatilhos. São conhecidos três tipos de angioedema hereditário. A doença é condicionada por diminuição do nível plasmático ou alteração da capacidade funcional do inibidor de C1, com aumento da bradicinina e da permeabilidade vascular, com consequente edema. Várias medidas devem ser tomadas no período perioperatório de forma a evitar uma crise aguda. A profilaxia deverá ser realizada durante a gravidez antes de qualquer procedimento cirúrgico, antes de procedimentos dentários, quando existe manuseamento da via aérea, nos doentes com episódios prévios de angioedema e quando há alterações significativas da volemia. A literatura é escassa no que que diz respeito à associação de angioedema hereditário e gravidez. Descrevemos um caso de sucesso de uma grávida com angioedema hereditário tipo I submetida a cesariana.


Subject(s)
Humans , Female , Pregnancy , Adult , Pregnancy Complications, Cardiovascular/therapy , Cesarean Section , Angioedemas, Hereditary/therapy , Perioperative Care
19.
Rev Assoc Med Bras (1992) ; 66(4): 502-506, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136216

ABSTRACT

SUMMARY OBJECTIVE To investigate the presence of the Angiopoietin 1 (ANGPT1) and Plasminogen (PLG) mutations in patients with Hereditary Angioedema (HAE) and normal C1 esterase inhibitor (C1-INH) levels, who do not harbor the F12 gene mutation. METHODS Patients clinically diagnosed with HAE but without C1-INH deficiency or dysfunction and F12 gene mutation were evaluated. DNA extraction, quantification, and dilution were performed at a concentration of 100 ng/µL, followed by a DNA amplification (PCR) for molecular evaluation of exon 2 of the ANGPT1 gene and exon 9 of the PLG gene for identification of mutations c.807G>T / p.A119S and c.988A>G / p.K330E, respectively. The PCR product was evaluated in 1% agarose gel electrophoresis. Sequencing was performed using the Sanger method. The electropherograms were analyzed using the FASTA® program. RESULTS DNA samples from 15 women were sequenced. Their ages ranged from 10 to 60 years and the normal C1 esterase and C4 inhibitor serum levels ranged from 22 to 39 mg/dL and from 10 to 40 mg/dL, respectively. No mutations were detected in the analyzed exons of ANGPT1 and PLG. However, a single-nucleotide polymorphism (SNP) was detected in two homozygotic and five heterozygotic patients. CONCLUSION Further studies are needed to evaluate these SNPs and scrutinize their potential for use as molecular markers of HAE and as novel therapeutic targets.


RESUMO OBJETIVO Investigar a presença das mutações no gene Angiopoietina (ANGPT1) e gene Plasminogênio (PLG) em pacientes com Angioedema Hereditário (AEH) com inibidor C1 esterase (C1-INH) normal e negativos para mutação do gene F12. MÉTODOS Foram avaliados pacientes com diagnóstico clínico de AEH sem deficiência ou disfunção de C1-INH e negativos para mutação do gene F12. Realizou-se extração, quantificação e diluição do DNA a uma concentração de 100 ng/uL, em seguida amplificação do DNA (PCR) para avaliação molecular do exon 2 do gene ANGPT1 e do exon 9 do gene PLG para identificação das mutações c.807G>T.p.A119S e c.988A>G p.K330E, respectivamente. O produto da PCR foi avaliado em eletroforese em gel de agarose 1%. Foi realizado o sequenciamento pelo método de Sanger. As análises dos eletroferogramas foram realizadas pelo programa FASTA®. RESULTADOS Foram sequenciadas amostras de 15 mulheres, idade entre 10 e 60 anos, com níveis séricos de inibidor de C1 esterase e C4 normais variando de 22 a 39mg/dL e 10 a 40mg/dL, respectivamente. Não foram identificadas mutações nos éxons analisados dos genes ANGPT1 e PLG. Entretanto no gene PLG foram encontrados polimorfismo de nucleotídeo único (SNP), em duas pacientes homozigotas e cinco heterozigotas. CONCLUSÃO Mais estudos sobre SNP são necessários para esclarecer estes achados pois eles podem ser utilizados como marcadores moleculares do AEH e alvo para novos tratamentos.


Subject(s)
Humans , Female , Child , Adolescent , Adult , Young Adult , Plasminogen/genetics , Angiopoietins/genetics , Angioedemas, Hereditary/genetics , Polymerase Chain Reaction , Complement C1 Inhibitor Protein , Middle Aged , Mutation
20.
Arq. Asma, Alerg. Imunol ; 3(4): 401-405, out.dez.2019. ilus
Article in Portuguese | LILACS | ID: biblio-1381349

ABSTRACT

A anafilaxia idiopática não apresenta etiologia conhecida. A sua prevalência é estimada entre 10-35% de todas as modalidades de anafilaxia. A sintomatologia apresentada é a mesma de qualquer outra anafilaxia: urticária, angioedema, ruborização, prurido, hipotensão arterial, taquicardia, manifestações gastrointestinais (disfagia, náusea, vômitos, cólicas abdominais, diarreia), asma, edema laríngeo, tontura e síncope. A mortalidade é rara. Não há transmissão genética, mas 40% dos pacientes são atópicos. É mais frequente nos adultos do que nas crianças, e principalmente em mulheres. É um diagnóstico de exclusão. Ocorre ativação mastocitária com desgranulação citoplasmática dos mediadores de anafilaxia (triptase, histamina, entre outros). É uma anafilaxia com boa resposta aos corticoides, e, portanto, caso não haja resposta adequada a doses eficazes de prednisona/prednisolona, o seu diagnóstico deve ser revisto. O diagnóstico diferencial da anafilaxia idiopática inclui: a mastocitose sistêmica indolente, síndromes de ativação mastocitária monoclonais, alergia à galactose-alfa-1,3 galactose, anafilaxia induzida por exercícios (com e sem dependência alimentar e medicamentosa), angioedema hereditário (congênito e adquirido), feocromocitoma, síndrome carcinoide, anafilaxia oral acarina, alergia ao Anisakis simplex, disfunção das cordas vocais, síndrome escombroide, alergia ao sêmen, alergia ao látex, manifestações psicossomáticas (síndrome do pânico, globus hystericus e a síndrome de Münchausen), bem como as tradicionais e mais frequentes modalidades de anafilaxia (alergia a alimentos, medicamentos e insetos). O tratamento na crise aguda da anafilaxia idiopática é o mesmo do que nas demais anafilaxias, incluindo a administração intramuscular imediata de epinefrina. Deve haver uma generosa e prolongada prescrição de corticoterapia oral, e também a instituição de medicação preventiva (anti-histamínicos anti- H1 e anti-H2, cetotifeno, albuterol oral, montelucaste, cromoglicato de sódio, e por último o omalizumabe). Os pacientes devem portar epinefrina autoinjetora e ser instruídos sobre como agir em caso de um episódio anafilático. Eles respondem bem à administração de epinefrina. A corticoterapia oral, por 4-6 semanas, pode induzir uma remissão completa.


Idiopathic anaphylaxis is a condition of unknown etiology. Its prevalence ranges from 10 to 35% of all cases of anaphylaxis. Clinical symptoms and signs are those of classic anaphylaxis, including urticaria, angioedema, flushing, itching, hypotension, tachycardia, gastrointestinal manifestations (dysphagia, nausea, vomiting, abdominal cramps, and diarrhea), asthma, laryngeal edema, dizziness, and syncope. Mortality is rare. There is no genetic transmission, but about 40% of patients are atopic. It is more common in adults than in children, affecting mainly women. It is considered a diagnosis of exclusion of other known forms of anaphylaxis. Mast cell activation occurs with cytoplasmatic degranulation of mediators of anaphylaxis (tryptase and histamine, among others). Because idiopathic anaphylaxis is a steroid-responsive condition, if it is not controlled with adequate doses of prednisone/prednisolone, the diagnosis should be challenged. The differential diagnosis of idiopathic anaphylaxis includes indolent systemic mastocytosis, clonal mast cell activation syndromes, galactose-alpha-1,3- galactose allergy, exercise-induced anaphylaxis (both food- and drug-dependent and -independent), hereditary angioedema (congenital and acquired), pheochromocytoma, carcinoid syndrome, oral mite anaphylaxis, Anisakis simplex allergy, vocal cord dysfunction, scombroid poisoning, semen allergy, latex allergy, psychosomatic conditions (panic attacks, globus hystericus, and Münchausen syndrome), and the classic forms of anaphylaxis (food, drug, and insect allergies). Treatment of acute idiopathic anaphylaxis is the same as in the other forms of anaphylaxis, including intramuscular epinephrine, but with prolonged oral corticosteroid therapy. It might also include other oral preventive medications (H1 and H2 antihistamines, ketotifen, oral albuterol, montelukast, sodium cromoglycate, and recently omalizumab). Patients should have an epinephrine auto-injector and be instructed on self-management of anaphylaxis. Good response to epinephrine is observed, and oral corticosteroid therapy for 4-6 weeks can induce complete remission.


Subject(s)
Humans , Prednisolone , Prednisone , Deglutition Disorders , Epinephrine , Panic Disorder , Anisakis , Adrenal Cortex Hormones/therapeutic use , Latex Hypersensitivity , Mastocytosis, Systemic , Albuterol , Angioedemas, Hereditary , Omalizumab , Food Hypersensitivity , Globus Sensation , Mast Cell Activation Syndrome , Histamine Antagonists , Anaphylaxis , Munchausen Syndrome , Panic , Patients , Asthma , Signs and Symptoms , Syndrome , Therapeutics , Adrenal Cortex Hormones , Diagnosis , Diagnosis, Differential
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