Patients With CRA May Have Asymptomatic Relatives Carrying HAE-Linked Mutations

A new study has found that solitary individuals with chronic recurrent angioedema (CRA) that does not respond to antihistamines can include patients with hereditary angioedema (HAE) with normal C1 inhibitor (HAEnCI).

The study, published in the Journal of Allergy and Clinical Immunology: In Practice, recommends searching for HAEnCI-linked mutations in these individuals to detect asymptomatic family members at risk of angioedema.

“Solitary HAEnCI patients without a family history of angioedema have been reported,” the authors explained. “We tested a large group of patients with CRA for the presence of one of the HAEnCI-linked gene mutations known to date. When an HAE-linked mutation was detected, we also investigated available relatives to identify asymptomatic mutation carriers bearing the risk for developing angioedema.”

The research team investigated 132 solitary patients with CRA without wheals and normal C1 inhibitor levels at a single center in Germany from January 1999 to April 2022. The cohort was nonresponsive to antihistamines. HAEnCI-linked mutations were analyzed by Sanger sequencing and biochemistry. When such mutations were identified, the patient’s relatives were examined and underwent genetic analyses.

Read more about HAE diagnosis

All of the solitary patients in the cohort initially reported that no family members had angioedema; however, a more detailed family history, confirmed by family members of those in whom HAE-specific mutations were found, revealed relatives with CRA.

While the majority (88%) of analyzed patients had no HAEnCI-linked mutation and therefore had idiopathic angioedema, 12% did have such a mutation, revealing a family history of HAEnCI. All relatives of these patients are at risk of also carrying the mutation and developing symptoms of HAE at some point in their lives.

The authors highlight the importance of taking a detailed family history and assessing HAEnCI-linked mutations in patients with solitary CRA to detect families with HAEnCI and individuals at risk of life-threatening angioedema. Without such study, asymptomatic carriers would go undetected, depriving them of genetic counseling and available treatments.

Reference

Bork K, Wulff K, Witzke G, Staubach P, Hardt J, Meinke P. Gene mutations linked to hereditary angioedema in solitary angioedema patients with normal C1 inhibitor. J Allergy Clin Immunol Pract. Published online February 12, 2023. doi:10.1016/j.jaip.2023.01.051