HAE Patients in Brazil Wait Nearly Two Decades for Diagnosis, Study Finds

There is a significant delay between symptom onset and an accurate diagnosis of hereditary angioedema (HAE) in Brazil, even in patients with a family history of the disease, according to a single-center study.

Patients waited an average of 17.7 years from symptom onset to diagnosis, with one experiencing a delay of 36 years.

Screening family members of patients with HAE — including those who don’t show any symptoms — is critical for earlier diagnosis and management, the researchers said.

The study, “Hereditary angioedema: a prospective study of a Brazilian single-center cohort,” was published in the International Journal of Dermatology.

While the prevalence of HAE in Brazil has been estimated at between 3,600 and 18,000 cases, only 210 HAE patients were included in the Brazilian registry from 2006 to 2010.

HAE-related swelling attacks may be triggered by stressful life events, local trauma, infections, medical procedures, or pregnancy, but may also occur in spontaneously, without any identifiable cause. Their frequency and location are also variable.

Researchers in Brazil set out to describe the sociodemographic and clinical features of HAE patients whose disease was caused by defects in the C1 inhibitor (C1-INH) protein, and who were followed at the Clementino Fraga Filho Hospital in Rio de Janeiro from 1989 to 2016.

“Only a few studies have evaluated HAE Latin American patients’ profiles, and as far as we know, this is the first one performed by a single Brazilian center in a prospective way,” the researchers said.

The analysis included 107 patients with HAE with C1-INH deficiency, including 105 with HAE type 1 – who have lower levels of the C1-INH protein – and two with HAE type 2, who produce a CI-INH protein with low activity, despite being found at normal or high levels.

The incidence of type 2 HAE was much lower than the 15%-20% expected, probably because of the limited availability diagnostic assays that measure CI-INH’s activity, the researchers said.

They collected prospective data from the 107 patients using a questionnaire, which asked for gender, age, family history of HAE, age at symptom onset, age at diagnosis, factors that triggered angioedema attacks, frequency and location of attacks, as well as education and socioeconomic status.

The group consisted mostly of women (67.3%), people with a medium level of education (47.7%), and medium to low socioeconomic status. They ranged in age from 12 to 73, with an average age of 38.

Researchers found that patients experienced their first symptoms around the age of 11.8, but were only diagnosed at a median age of 29, representing a 17.7-year delay from early disease manifestations to diagnosis.

Most patients (86.9%) reported a family history of the disease, and still experienced a considerable delay in diagnosis.

The researchers said “screening of familial members, including asymptomatic individuals, is critical for earlier diagnosis.”

Most patients (95.8%) had some sort of triggering factor before a swelling attack, and episodes were preceded by at least one precursor symptom — such as numbness or itching — in nearly half of patients (47.9%).

Attacks were mostly moderate (24.3%) or severe (55.1%), lasted between three and five days, and occurred mainly in the skin (95.8%), gastrointestinal tract (88.5%), or in the airways (65.6%). A quarter of these patients were admitted to intensive care units, and 8.3% required intubation or tracheostomy – a surgical procedure that creates an airway in the neck.

Attacks were more severe in women than in men, pointing to the “need for an awareness of the disease by gynecologists and obstetricians, since it can complicate pregnancy, labor, and delivery,” the researchers wrote.