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

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Patients with hereditary angioedema (HAE) are more likely to develop comorbidities, or co-existing conditions, such as cardiovascular and autoimmune diseases than the general population, a Swedish database study reports.

The findings highlight the need for awareness and prevention of these conditions in patients with HAE, according to researchers.

The study, “Comorbidities in hereditary angioedema — A population-based cohort study,” was published in the journal Clinical and Translational Allergy.

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HAE is a type of angioedema caused by mutations in the SERPING1 gene, which carries instructions for making a protein called C1-INH. In HAE type 1, C1-INH production is impaired, while in HAE type 2, the protein is dysfunctional.

C1-INH inhibits the activation of the complement system — part of the immune system involved in the body’s inflammatory response — and regulates other signaling pathways that control blood clotting and inflammation.

In patients with HAE type 1 and type 2, deficient C1-INH activity also leads to the activation of the contact system, a signaling cascade that promotes blood clotting and inflammation.

The activation of the complement system, as well as the contact system, is thought to result in the development of comorbidities in people with HAE. In fact, an association between autoimmune disorders, such as systemic lupus erythematosus (SLE), and HAE has been previously reported.

However, “the prevalence of other dysregulated immune responses, for example, the prevalence of allergic disease and asthma, has not been investigated in HAE,” the researchers wrote.

To address this gap, a research team in Sweden set out to determine the risk of several comorbidities in HAE.

They identified patients with HAE by contacting most of the doctors who treat HAE and by using databases at clinical immunology laboratories in Sweden. Data from the general population was retrieved from the Swedish National Population Register. Information on the prescription of medications from 2006 to 2019 was obtained from the National Prescription Register.

A total of 239 HAE patients were identified and compared to a group of 2,383 people from the general population. Most patients had type 1 HAE (90.4%) and the remaining (9.6%) had type 2. Among patients with HAE included in the study, 28% were 20 to 39 years old, and 27.6% were 40 to 59 at study enrollment.

Statistical analyses showed that the likelihood of HAE patients developing cardiovascular disease was 1.83 times greater than that of the general population. Additionally, the risk of arterial thrombosis — a condition characterized by the formation of a blood clot in an artery — was found to be 6.74 greater in HAE patients. Similarly, the risk of venous thromboembolic disease (blood clots in a vein) was 4.20 greater in people with HAE compared with controls.

The researchers also estimated the odds of developing an autoimmune disease were 1.65 times higher in people with HAE. Particularly, lupus was nearly 72 times more likely to occur in HAE patients than in the general population.

Study findings also showed the risk of having two or more autoimmune diseases was higher in HAE patients, and similar to previous reports, autoimmune hypothyroidism and SLE were found to be more frequent in women than in men. Hypothyroidism is a condition in which the thyroid, a gland found in the neck, fails to produce and release adequate amounts of hormones into the bloodstream.

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Hyperlipidemia — a condition in which excessive levels of fatty molecules are found in the blood — as well as allergies, asthma, and atopic dermatitis (red and itchy skin) were also more common in HAE patients. The researchers found no increased risk of cancer or death among HAE patients.

Prescription rates of medications for high blood pressure, hypothyroidism, and hyperlipidemia were also higher for HAE patients than for the general population.

“Taken together, the results of this study points to the importance of awareness regarding thromboembolic [blood clotting] and autoimmune disease among HAE patients,” the researchers wrote. “Future [preventive] interventions may modify these risks.”