Acquired angioedema due to C1 inhibitor deficiency: real-world clinical characteristics and treatment outcomes.

Introduction: Acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) is a rare bradykinin-mediated condition that may mimic hereditary angioedema (HAE). Management is largely extrapolated from HAE data. Therefore, retrospective observations in AAE-C1INH are particularly valuable for informing future approaches. This study aimed to evaluate the clinical characteristics, underlying conditions, and treatment outcomes of patients with AAE-C1INH. Methods: We conducted a retrospective cohort study of adult patients diagnosed with AAE-C1INH, with a comprehensive review of demographic and clinical features. Results: Among 587 patients with recurrent angioedema, 1.7% had AAE-C1INH. Median onset age was 56.5 years (45.5-66.75), median follow-up was 60.5 months (23.25-66.5), and 20% were female. Clonal hematologic neoplasms were present in 60% of patients and monoclonal gammopathy of undetermined significance in 30%, with angioedema preceding the diagnosis of the underlying condition in 60% of cases. Long-term prophylaxis was required in 50% of patients. Antifibrinolytic agents showed limited efficacy, whereas attenuated androgens were associated with a marked reduction in attack frequency. Rituximab-based therapy effectively controlled angioedema, although relapse occurred during extended follow-up. Complete remission under Bruton's tyrosine kinase (BTK) inhibition was observed despite persistently low complement levels; however, concurrent withdrawal of renin-angiotensin system blockers represents a potential confounder. Complement levels were observed to parallel treatment response in most patients, whereas this association was not observed in the patient receiving a BTK inhibitor. Conclusion: In this rare, well-characterized cohort with extended follow-up, angioedema frequently represented the earliest clinical manifestation of AAE-C1INH, preceding recognition of the underlying disorder. Antifibrinolytic prophylaxis showed limited benefit, whereas attenuated androgens were associated with reduced attack frequency. Furthermore, therapies targeting the underlying lymphoproliferative condition, including rituximab-based regimens and BTK inhibition, were associated with meaningful clinical benefit. These findings support an individualized, etiology-driven management approach and provide practical insights for clinicians managing this rare condition.