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Epidemiology of bradykinin-mediated angioedema: a systematic investigation of epidemiological studies

BACKGROUND: Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management.

METHODS: We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria.

RESULTS: We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark.

CONCLUSIONS: Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.

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