Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases)

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

Angioedema hereditario, una enfermedad de fácil confusión en su diagnóstico / Hereditary angioedema, a disease of easily diagnosis confusion

El angioedema hereditario es una enfermedad genética rara, autosómica dominante, con una aparición de 1:10 000 a 1:50 000 habitantes, que presenta como síntoma principal episodios de edema definido, doloroso, deformante con ausencia de prurito, generalmente localizado en las extremidades. El diagnóstico se realiza basado en anamnesis, examen físico y determinación de C4, C1 - INH, cuyos niveles séricos deben encontrarse bajos. Se presenta el caso de un paciente masculino de 33 años que asiste a consulta con un edema deformante en el rostro y en las extremidades superiores, refiere que en su familia un abuelo presentó un cuadro semejante y sus dos hijos tienen estos síntomas. Los exámenes realizados reflejaron: C3: 87 mg/dL, C4: 10 mg/dL y actividad funcional de C1-INH: 33 por ciento; el resto de los estudios hormonales e inmunológicos mostraron valores dentro de los rangos normales. Se diagnosticó como angioedema hereditario tipo II y se impuso tratamiento profiláctico con Danazol (200 mg); el paciente lleva cuatro meses sin episodios(AU)

Hereditary angioedema is a rare genetic autosomal dominant disease with an appearance from 1:10 000 to 1:50 000, which main symptom is defined episodes of painful deforming edema with absence of pruritus, usually located in extremities. Diagnosis is based on anamnesis, physical examination and determination of C4, C1-INH, where low serum must be found. We present a male patient aged 33, who attends a consultation with disfiguring edema in the face and upper extremities reporting that in his family a grandfather presented a similar symptom as well as his two sons. The tests made reflected: C3: 87 mg / dl, C4: 10 mg / dl and functional activity of C1-INH: 33 percernt; other hormonal and immunological studies showed values within normal ranges. He was diagnosed as hereditary angioedema type II and received prophylactic treatment with Danazol (200 mg); the patient has now been four months without episodes(AU)

Angioedema hereditario: Historia familiar y manifestaciones clínicas en 58 pacientes / Hereditary angioedema: Family history and clinical manifestations in 58 patients

El angioedema hereditario (AEH) es una enfermedad rara, autosómica dominante, caracterizada por episodios de angioedema que comprometen la piel, el tracto gastrointestinal y la laringe. Analizamos las características epidemiológicas y clínicas en una serie de 58 pacientes, 53 (91%) con diagnóstico de AEH tipo I y 5 (9%) con tipo II. La edad media al inicio fue de 10.8 ± 9.5 años (0.1 a 59) y de 25.8 ± 16.2 años (2 a 77) en el momento del diagnóstico, con un retraso diagnóstico de 15.3 ± 14.3 años. El promedio de ataques en los 6 meses previos a la consulta fue de 7.4 ± 7.6 (0 a 40). Cincuenta y cuatro (93%) presentaron ataques cutáneos, 50 (86%) abdominales, 24 (41%) laríngeos y 24 (41%) cutáneos y abdominales combinados. Veintisiete (46.5%) nunca utilizaron medicación preventiva para la enfermedad y 17 (29%) recibieron danazol en diferentes dosis por diferentes periodos de tiempo. Durante los ataques, 15 (26%) pacientes recibieron C1 inhibidor endovenoso alguna vez, 7 (12%) recibieron plasma fresco y 40 (69%) tratamiento sintomático. Ansiedad o situaciones de estrés y traumatismos fueron los desencadenantes más frecuentes. Identificamos a 6 (10%) pacientes como primera mutación y a 52 (90%) con historia familiar previa. Analizamos 20 troncos familiares identificando 205 individuos en riesgo de heredar la enfermedad, 109 (53%) de ellos con síntomas o diagnóstico AEH. El total de individuos con síntomas de AEH fue de 145, de los cuales 19 (13%) murieron por asfixia. Disminuir el retraso diagnóstico y ofrecer una terapéutica adecuada son desafíos a afrontar en el AEH.

Hereditary angioedema (HAE) is a rare autosomal dominant disease, characterized by episodes of edema typically involving the skin, gastrointestinal tract and larynx. We here describe the epidemiologic and clinical characteristic of a series of 58 patients with diagnosis of HAE, 53 (91%) type I and 5 (9%) type II. The mean age at first symptom was 10.8 ± 9.5 years and the mean age at diagnosis was 25.8 ± 16.2 years old, with a diagnosis delay of 15.3 ± 14.3 years. The mean number of attacks in the previous 6 months was 7.4 ± 7.6 range 0 to 40. Fifty four (93%) had cutaneous attacks, 50 (86%) abdominal attacks, 24 (41%) laryngeal attacks and 24 (41%) combined cutaneous and abdominal attacks. Twenty seven (46.5%) patients never received preventive treatments and 17 (29%) received danazol in different doses for different periods of time. During the attacks, 15 (26%) patients were treated with C1 inhibitor at least once, 7 (12%) with fresh frozen plasma and 40 (69%) received only supportive treatment. Stress and trauma were identified as attacks triggers. Six (10%) patients were first mutation and 52 (90%) had HAE ancestors. We reconstructed 20 kindred, identifying 205 individuals at risk of inheriting the disease, 109 (53 %) of them had signs or laboratory diagnosis of HAE. The total number of identified HAE individuals was 145, 19 (13%) died with asphyxia. So, shortening of diagnosis delay and appropriate treatment of HAE are a challenge to be fulfilled.