RESUMO
INTRODUCTION: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. METHODS: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. RESULTS: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. CONCLUSIONS: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.
Assuntos
Angioedemas Hereditários/epidemiologia , Adolescente , Anafilaxia/etiologia , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/terapia , Brasil/epidemiologia , Criança , Pré-Escolar , Diagnóstico Tardio , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Vigilância em Saúde Pública , Qualidade de VidaRESUMO
BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare condition with clinical features similar to those of HAE with C1-INH deficiency. Mutations in the F12 gene have been identified in subsets of patients with HAE with normal C1-INH, mostly within families of European descent. OBJECTIVES: Our aim was to describe clinical characteristics observed in Brazilians from 42 families with HAE and F12 gene mutations (FXII-HAE), and to compare these findings with those from other populations. METHODS: We evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives. RESULTS: Genetic analysis revealed that of the 195 subjects, 134 individuals (77.6% females) carried a pathogenic mutation in F12. The T328K substitution was found in 132 individuals, and the c.971_1018+24del72 deletion was found in 2 patients. The mean age at onset of symptoms in patients with FXII-HAE was 21.1 years. The most common symptoms were subcutaneous edema (85.8% of patients), abdominal pain attacks (69.7%), and upper airway edema (32.3%). Of male individuals carrying F12 mutations, 53.3% (16 of 30) were symptomatic. Compared with reports from Europe, fewer female patients (68.6%) reported an influence of estrogen on symptoms. CONCLUSIONS: Our study included a large number of patients with FXII-HAE, and, as the first such study conducted in a South American population, it highlighted significant differences between this and other study populations. The high number of symptomatic males and patients with estrogen-independent FXII-HAE found here suggests that male sex and the absence of a hormonal influence should not discourage clinicians from searching for F12 mutations in cases of HAE with normal C1-INH.