Outcomes of long term treatments of type I hereditary angioedema in a Turkish family

Abstract: Background: Hereditary angioedema is a rare autosomal dominantly inherited immunodeficiency disorder characterized by potentially life-threatening angioedema attacks. Objective: We aimed to investigate the clinical and genetic features of a family with angioedema attacks. Methods: The medical history, clinical features and C1-INH gene mutation of a Turkish family were investigated and outcomes of long-term treatments were described. Results: Five members had experienced recurrent swellings on the face and extremities triggered by trauma. They were all misdiagnosed as familial Mediterranean fever (FMF) depending on frequent abdominal pain and were on colchicine therapy for a long time. They had low C4 and C1-INH protein concentrations and functions. A mutation (c.1247T>A) in C1-INH gene was detected. They were diagnosed as having hereditary angioedema with C1-INH deficiency (C1-INH hereditary angioedema) for the first time. Three of them benefited from danazol treatment without any significant adverse events and one received weekly C1 esterase replacement treatment instead of danazol since she had a medical history of thromboembolic stroke. Study limitations: Small sample size of participants. Conclusion: Patients with C1-INH hereditary angioedema may be misdiagnosed as having familial Mediterranean fever in regions where the disorder is endemic. Medical history, suspicion of hereditary angioedema and laboratory evaluations of patients and their family members lead the correct diagnoses of hereditary angioedema. Danazol and C1 replacement treatments provide significant reduction in hereditary angioedema attacks.

Angioedema hereditario en Medellín, Colombia: evaluación clínica y de la calidad de vida / Hereditary angioedema in Medellín (Colombia): Clinical evaluation and quality of life appraisal

Introducción. El angioedema hereditario es una inmunodeficiencia primaria de carácter autosómico dominante, debida a un déficit en la proteína inhibidora del factor C1 y caracterizada por episodios recurrentes de edema subcutáneo y de las mucosas. Las impredecibles y frecuentes crisis de angioedema afectan la calidad de vida de los individuos que las padecen. Objetivo. Analizar las características clínicas de una familia con un caso índice de angioedema hereditario y determinar el impacto de la enfermedad en la calidad de vida. Materiales y métodos. En el estudio se incluyeron 26 miembros de la familia, a 25 de los cuales se les midieron los niveles sanguíneos del factor C4 del complemento y del inhibidor de C1 antigénico y funcional. Se utilizaron dos instrumentos, el SF-36 para evaluar la salud del adulto y el KIDSCREEN-27 para la calidad de vida de niños y adolescentes. Resultados. El 83 % de los individuos que reportaron síntomas cumplían con los criterios serológicos del angioedema hereditario de tipo I: valores bajos del factor C4 del complemento y del inhibidor de C1 cuantitativo (antigénico) y cualitativo (funcional). Se encontró que la calidad de vida en cuanto al bienestar psicológico y el desempeño emocional de los pacientes, se veía considerablemente afectada por los síntomas de la enfermedad. Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.

Introduction: Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. Objective: To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Materials and methods: Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Results: Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. Conclusion: This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study / Icatibanto, um inibidor de receptor 2 de bradicinina, para ataques de angioedema hereditário: estudo experimental prospectivo de coorte sem grupo controle

CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients. .

CONTEXTO E OBJETIVO: O angioedema hereditário (AEH) com deficiência de inibidor de C1 manifesta-se por episódios recorrentes de edema envolvendo pele, trato respiratório superior e gastrointestinal. Pode ser letal por asfixia. O objetivo foi avaliar a resposta à terapia dos ataques com icatibanto, inibidor do receptor de bradicinina, recentemente introduzido no Brasil. TIPO DE ESTUDO E LOCAL: Estudo experimental prospectivo de coorte, sem grupo controle, da eficácia e segurança do icatibanto em paciente com AEH. MÉTODOS: Pacientes com diagnóstico confirmado de AEH foram incluídos de acordo com os sintomas, independentemente do tempo de início do ataque. Icatibanto foi administrado segundo protocolo aprovado no Brasil. A gravidade do sintoma foi estabelecida continuamente e os eventos adversos foram monitorados. RESULTADOS: 24 ataques em 20 pacientes com AEH foram tratados (19 F:1 M; 19-55 anos; mediana 29 anos). Os sintomas foram: edema subcutâneo (22/24), dor abdominal (15/24) e obstrução de vias aéreas superiores (10/24). O tempo para o início do alívio foi: 5-10 minutos, 5/24 (20,8%); 10-20, 5/24 (20,8%); 20-30, 8/24 (33,4%); 30-60, 5/24 (20,8%) e 2 horas, 1/24 (4,3%). O tempo para a resolução completa variou de 4,3-33,4 horas. Somente efeitos adversos nos locais das injeções foram relatados. Eritema leve a moderado e/ou sensação de ardor foram relatados por 15/24 pacientes, prurido em 3, e 6 não tiveram efeitos adversos. CONCLUSÃO: Pacientes com AEH tipo I receberam icatibanto com pronta resposta; a maioria teve melhora na gravidade dos sintomas em 30 minutos. Eventos adversos locais ocorreram em 75% dos pacientes. .

Angioedema hereditario / Hereditary angioedema

Se presenta el caso de una mujer de 46 años, quien consulta por lesiones dérmicas episódicas de 28 años de evolución, consistentes en edema doloroso ocasionalmente pruriginoso, súbito, recurrente, familiar, que compromete varias regiones corporales incluyendo la laringe. Por la gravedad de los episodios ha requerido repetidas hospitalizaciones en las que se ha recuperado mediante tratamiento sintomático. Se encuentran valores séricos de C3 165.5 mg/dL, C4 1 mg/dL, CH50 < 256 U, e inhibidor de C1 38 mg/dL. Se realiza diagnóstico de angioedema hereditario tipo I y se inicia tratamiento con antifibrinolíticos y andrógeno con mejoría de los síntomas. Se hace énfasis en la necesidad de sospechar la enfermedad clínicamente en pacientes con episodios recurrentes de angioedema sin urticaria con el fin de instaurar el tratamiento adecuado, por falla en dicha sospecha, dos de los familiares de la paciente infortunadamente fallecieron. (Acta Med Colomb 2012; 37: 34-37).

A 46 year-old woman affected by familiar, recurrent episodes of skin lesions with painful, occasionally pruriginous angioedema who had been hospitalized because of laryngeal compromise is presented. Laboratory results include C3: 165.5 mg/dL, C4: 1 mg/dL, CH50 < 256 Units, and C1 inhibidor 38 mg/dL. Hereditary angioedema Type I is diagnosed, patient is currently on treatment with anti-fibrynolytic and androgen, obtaining clinical improvement. A clinical emphasis in the diagnosis of Hereditary angioedema is performed since misdiagnosis of this disease may lead to death as it happened to two patients's relatives. (Acta Med Colomb 2012; 37: 34-37).