Rare angioedema types marked by time to diagnosis, attack differences
Findings: Treatment guidelines, therapies needed for HAE nC1-INH, AE-UNK
There are notable differences between hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and idiopathic angioedema of unknown etiology (AE-UNK), even though they share many features, a real-world Canadian study indicates.
Some of the differences include the time to reach a diagnosis, attack triggers and characteristics, and treatment responses. The findings underscore the need for more research into these rare angioedema types and for guidelines about how to diagnose and treat them.
“These results suggest an unmet need for treatment guidelines and therapies specifically for patients with HAE nC1-INH and AE-UNK, and better understanding of the pathophysiology [mechanisms] accounting for the reported differences between the two,” the researchers wrote.
The study, “Real-world outcomes of patients with hereditary angioedema with normal C1-inhibitor function and patients with idiopathic angioedema of unknown etiology in Canada,” was published in Allergy, Asthma and Clinical Immunology.
Angioedema refers to swelling in the deeper layers of the skin or mucus membranes. HAE is a form of the disease caused by a genetic mutation. In most patients, mutations in the gene that encodes the C1-INH protein cause HAE, but in HAE nC1-INH, mutations in other genes are the cause. Unlike the more common subtypes where C1-INH levels and/or activity are low, in HAE nC1-INH the protein’s levels and function are normal.
People who have symptoms of recurrent angioedema, but no family history of the condition and in whom no clear cause can be identified, may be considered to have AE-UNK.
Both HAE nC1-INH and AE-UNK are very rare types of angioedema, and little is known about their characteristics and clinical outcomes, leading scientists to assess and compare data from 37 people with HAE nC1-INH and 23 with AE-UNK who were treated at centers in Canada between 2012 and 2022.
“This is the first study to evaluate the demographics, treatment response, and healthcare resource utilization among patients with HAE nC1-INH and AE-UNK, across Canada,” the researchers wrote.
Differences between types of angioedema
The median age at the onset of symptoms was the early 20s in both angioedema types and the median age at diagnosis was the early to mid 30s. The median time between the onset of symptoms and diagnosis differed between the types, seven years with HAE nC1-INH and two years with AE-UNK.
The delay “underscores the current difficulties in making these diagnoses given the absence of confirmatory tests for most patients, rarity of the diseases, and requirement for highly specialized physician assessment,” the researchers wrote. “This could potentially be addressed by establishing consensus guidelines specifically for these conditions that describe diagnostic and therapeutic approaches based on the best available evidence and collective experience.”
Triggers that prompted swelling attacks also differed, as did attack locations. Those with HAE nC1-INH were much more likely to report that their swelling was triggered by stress or by medications containing estrogen, such as birth control pills. In the absence of specific angioedema treatments, swelling in the extremities or the digestive tract also were more common with HAE nC1-INH.
Patterns of treatment and usage of healthcare resources were similar in HAE nC1-INH and AE-UNK. In both types, about 9 in 10 patients used on-demand medications to control swelling, The most common being icatibant, which is sold as Firazyr and generics, and C1-INH products.
In both angioedema types, the main medicines used for preventive treatment were C1-INH products and tranexamic acid. Two or more preventive therapies were being used simultaneously by 22% of patients with HAE nC1-INH and 13% with AE-UNK.
Preventive treatment lowered the rates of swelling attacks in both disease types, though “the mean number of attacks after treatment initiation was still high,” with many patients having multiple swelling attacks per month despite treatment to prevent them.
“This suggests a significant unmet need for effective preventative treatments for these patients,” wrote the researchers, who noted the data highlight a need for more research into these rare angioedema types to help guide optimal care for patients.
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