HAE-associated Mortality in Brazil Tied to Income Levels

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Death due to breathing difficulties associated with hereditary angioedema (HAE) remains a concern in Brazil, highlighting that misdiagnosis and a lack of treatment access in lower-income countries may contribute to increased mortality rates, a recent study highlights.

While HAE-associated deaths have declined significantly in recent years within high-income countries, HAE, “remains a threat to life” in Brazil, the researchers wrote, adding that the findings, “advocate for minimizing the gap in access to diagnostic and treatment resources.”

The study, “Investigation of Mortality of Hereditary Angioedema in a Reference Center in Brazil,” was published in The Journal of Allergy and Clinical Immunology: In Practice. 

HAE is an inherited form of angioedema characterized by sudden, temporary swelling that affects the deep layers of the skin. Such attacks in the mouth and throat can lead to potentially life-threatening breathing difficulties.

While advances in the diagnosis and treatment of HAE have led to improved prognoses for many people, high treatment costs may prevent adequate access to care in countries with fewer resources, leading to disparities in HAE-associated mortality rates.

A research team in Brazil aimed to evaluate the incidence of mortality among individuals who were evaluated at a large reference center in Brazil and in their close relatives.

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HAE Patients Found to Be at Higher Risk of Developing Other Diseases

Overall, researchers analyzed data from 433 people from 46 families with symptoms of HAE. Among them, 179 people were found to have a confirmed HAE diagnosis.

“The availability and quality of the confirmatory tests in middle-income countries may influence this noted disproportion of suspected and confirmed cases,” the researchers wrote.

Deaths were reported in 75 cases among 24 families. A total of 10 people were diagnosed with HAE before they died, while in the remaining 65 people the diagnosis was made postmortem.

About half of the reported deaths (52%) were determined to be the result of asphyxiation caused by a swelling of the airways, and the other half (48%) were attributed to other causes.

Of the asphyxiation-related deaths, 16 occurred from 2000 to 2020, while the remaining 23 occurred from 1950 to 2ooo. This finding is notable, the researchers said, because studies in other high-income countries generally have not seen HAE-related death in recent years.

While many individuals who experienced asphyxiation died in the hospital (23 patients), 16 died at home or en route to the hospital. The median time from symptom onset to seeking medical care was four hours, and the median time to death was eight hours. Throat pain or discomfort was the most common symptom, experienced by 71.8% of people who died from airway swelling.

No patients who died from asphyxiation received any medication specific to HAE, but 18 people received medications without proven effectiveness in HAE, such as antihistamines, adrenaline, or antibiotics.

Also, a tracheostomy or cricothyroidotomy — two emergency surgical procedures used to open the airways — were performed or attempted in 12 patients, and intubation was attempted or accomplished in two people.

“The poor accessibility to first-line therapies for long-term prophylaxis [disease prevention] and on-demand treatment in Brazil affects these patients’ quality of life and directly impacts HAE mortality,” the researchers wrote.

“Patients may seek less medical assistance when needed as they might feel powerless in their disease treatment,” the team wrote.

Death certificates from those who died from airway swelling correctly cited an HAE attack as the cause of death in five of 39 cases. About 23% of cases were misdiagnosed as allergy attacks on the death certificate, while the death was determined to be of undetermined caused in seven people. Original records could not be accessed for the remaining six patients.

Overall, the lifespan of those who died from airway swelling was reduced by 20 years compared with those who died from other causes, although this difference was not statistically significant. Specifically, those who died from airway swelling died at a mean age of 39.3 years, whereas those who died from other causes were a mean age of 59.8 years.

“High mortality continues to be a reality in middle-income countries” the researchers wrote, noting that in these countries, “rare diseases, such as HAE, are usually neglected and are disadvantaged when these assessments are made. Having knowledge of the situation experienced by these patients is the first step toward measures aimed at their improvement.”

Patient education, access to remote or virtual healthcare assistance, and improved public policy and research efforts are tools that could help lower mortality rates for HAE in countries with fewer resources, the researchers said.