Hereditary Angioedema With Normal C1 Inhibitor Shows Greater Burden
Key Clinical Summary
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Hereditary angioedema with normal C1 esterase inhibitor (HAE-nl-C1INH) was associated with more frequent attacks and worse health-related quality of life than HAE Type 1/2 in an 89-adult survey.
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Diagnosis before age 18 was less common with HAE-nl-C1INH, while orofacial-laryngeal swelling and frequent physician visits were more common.
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The findings support improved diagnosis, targeted treatment strategies, and further research into HAE-nl-C1INH.
Adults with hereditary angioedema with normal C1 esterase inhibitor reported greater disease burden than those with HAE Type 1/2, according to a cross-sectional online survey conducted from June 2020 through September 2021. Participants with HAE-nl-C1INH reported more frequent attacks, greater health care utilization, and significantly worse health-related quality of life.
Study Findings
The study compared 44 adults with HAE Type 1/2 and 45 with HAE-nl-C1INH. HAE Type 1 involves low C1 esterase inhibitor levels, whereas Type 2 involves dysfunctional C1 esterase inhibitor; HAE-nl-C1INH involves normal levels.
Researchers collected patient-specific information and health care utilization data. Analyses used Fisher exact tests, t tests, and odds ratios with 95% confidence intervals. No significant differences were observed between groups in demographics, treatment characteristics, or HAE triggers.
Only 4% of participants with HAE-nl-C1INH were diagnosed before age 18, compared with 32% with HAE Type 1/2 (OR, 0.10; 95% CI, 0.02–0.50). Frequent attacks were reported by 47% versus 14%, respectively (OR, 5.5; 95% CI, 2.0–15.7).
Orofacial-laryngeal swelling was also more common in the normal-C1-inhibitor group: 31% versus 16% (OR, 2.3; 95% CI, 1.1–4.7). More than one physician visit per month was reported by 31% versus 11% (OR, 3.5; 95% CI, 1.1–10.8).
Concomitant conditions were reported by 93% of participants with HAE-nl-C1INH and 77% with HAE Type 1/2 (OR, 3.8; 95% CI, 1.6–9.2). Total health-related quality-of-life scores were significantly worse with HAE-nl-C1INH: 53.6 versus 38.2 (P = .0001).
Clinical Implications
The differences encompassed attack frequency, swelling location, physician visits, concomitant conditions, and quality of life. These findings describe a broader burden among surveyed adults with HAE-nl-C1INH, despite the absence of significant differences in reported treatment characteristics or triggers.
For clinicians, the comparison highlights the authors’ call for improved diagnosis and targeted treatment strategies. The lower proportion diagnosed before age 18 documents a difference in diagnosis timing between groups, although the supplied study text does not explain its cause.
The cross-sectional survey provides comparative patient-reported data. It does not establish why the groups differed or identify a specific treatment strategy that improves outcomes in HAE-nl-C1INH.
The study authors concluded that participants with HAE-nl-C1INH experienced significantly greater disease burden than those with HAE Type 1/2. They emphasized improved diagnosis, targeted treatment strategies, and a deeper understanding of the condition’s prevalence and pathophysiology. The supplied text includes no named expert, institutional affiliation, location, or direct quotation.
Across this 89-adult survey, HAE-nl-C1INH was associated with greater reported burden across several clinical and quality-of-life measures. The authors identified diagnosis, treatment strategies, and research into prevalence and disease mechanisms as priorities for further work.
Reference:
Jones D, Narsipur N, Wade SW, et al. Patient-reported disease burden and health care utilization of HAE-nl-C1INH: insights from a real-world survey. Clin Exp Med. 2026; 26(1):108. doi: 10.1007/s10238-025-02010-5.
