Hereditary Angioedema Patients Face High Rates of Autoimmune Conditions, Allergies

In a recent study, participants with hereditary angioedema reported a greater prevalence of specific comorbidities—namely, autoimmune conditions, allergies, and asthma—compared to the general population.1

“Over two-thirds of respondents reported having at least one autoimmune condition (e.g., psoriasis, RA, inflammatory bowel disease, chronic urticaria, lupus, and psoriatic arthritis), allergy (e.g., medication, pollen, and pets/dander), or asthma, with many of the respondents reporting at least two of these conditions,” wrote investigators, led by Paul K. Keith, from the department of medicine at McMaster University in Hamilton, Canada.

Hereditary angioedema (HAE), a rare, potentially life-threatening genetic disorder, is characterized by swelling, most frequently involving the face, airways, extremities, genitals, gastrointestinal tract, and mesenteric structures. HAE often faces diagnostic challenges.

Earlier this month HCPLive spoke with Timothy Craig, DO, from Penn State, about HAE diagnosis challenges at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting in San Diego, who said that a main limitation of diagnosing this disorder is recognition—or rather, the lack thereof.2 A patient may go into the emergency room for abdominal pain and the ER doctors may think they are just seeking narcotics; or, if they have swelling in the face, they might receive unnecessary surgery.

Thus, due to the challenges of HAE diagnosis, it is important to understand the prevalent comorbidities in this rare disorder. Investigators recognized the need to identify HAE’s comorbidities and how they may affect HAE treatment.1

Keith and colleagues sought to identify comorbidities and assess their prevalence in patients with HAE compared to the general Canadian population. The team conducted the study via a quantitative self-administered anonymous online questionnaire from October 13, 2022, to January 11, 2023.

The sample included 123 participants (81% female; mean age 44.9 years) who had HAE and were enrolled in the CSL Behring patient support program. Participants received the following HAE treatments: C1-esterase inhibitor (subcutaneous or intravenous), lanadelumab, icatibant, danazol, and tranexamic acid.

By HAE type, there were 60% with HAE-1/HAE-2, 25% with HAE Normal C1-INH (nC1-INH), and 16% who were unsure of their HAE type. A large percentage of participants were on long-term prophylaxis (85%).

More than half (69%) of participants reported having either an autoimmune condition, asthma, or allergy. Participants with HAE reported a greater prevalence in autoimmune conditions, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, chronic urticaria, lupus, and psoriatic arthritis, compared to the general population (31% vs 5 – 8%).

“One of the explanations for this has been that the reduction of early complement components, specifically C4, in HAE patients, could affect the clearance of immune complexes, and immune regulation, which may in turn lead to autoimmunity,” investigators wrote. “The role of sex hormones in the pathogenesis of autoimmune diseases has been another possible explanation, particularly the influence of serum estrogen levels [33]. Notably, the pathophysiology of HAE nC1-INH is poorly understood but the role of sex hormones has been hypothesized, considering the higher prevalence of women living with HAE nC1-INH compared to men.”

Similarly, patient-reported allergies were 2 times greater than the general population (54% vs 27%) and asthma rates were nearly 2 times greater than the general population (17% vs 8 – 11%). For allergies, participants reported high rates of being allergic to medication, pollen, pets/dander, dust mites, and food. However, investigators noted that this finding could be overestimated since many patients with HAE are diagnosed with allergies first before being correctly diagnosed.

The study also found that patients with HAE also had increased mobility issues, which could be caused by the swelling of the extremitites.

“This study confirms that HAE patients suffer from more than just the symptoms of angioedema. HAE is a condition that appears to be associated with many comorbidities compared to the general population,” investigators concluded. “In particular, these include an increased risk of autoimmune conditions, allergies, and asthma, contributing to a less positive overall health status. It is important to increase awareness among physicians who care for HAE patients on the relationship between HAE and comorbidities, to optimize the care of these patients.”

References

1. Keith PK, Lacuesta G, Goodyear D, Betschel SD, Yap B, Dansereau MF, Tanios N, El-Sayegh R, Machnouk M, Mahfouz H, Martin A, Waserman S. Comorbidities in Canadian patients with hereditary angioedema: a quantitative survey study. Allergy Asthma Clin Immunol. 2025 Mar 19;21(1):13. doi: 10.1186/s13223-025-00953-8. PMID: 40108700; PMCID: PMC11924777.

2. Craig, T. Hereditary Angioedema Diagnosis Challenges, with Timothy Craig, DO. HCPLive. March 11, 2025. https://www.hcplive.com/view/hereditary-angioedema-diagnosis-challenges-timothy-craig-do. Accessed March 21, 2025.