C1 esterase inhibitor (C1-INH) response as a supportive diagnostic criterion for patients with suspected hereditary angioedema with normal C1-INH.

Diagnosis of hereditary angioedema (HAE) with normal C1INH level (HAE-nl-C1INH) is based on several criteria, including either an associated genetic variant identified or family history of recurrent angioedema plus lack of high-dose antihistamine response. A rapid, durable response to bradykinin-targeted medication is considered supportive, and this study aimed to evaluate the use of recombinant human C1 esterase inhibitor (rhC1-INH) in this regard. A retrospective medical records review was conducted for angioedema/HAE codes. Thirty-one patients with HAE-nl-C1INH were identified (female, 87.1%; mean age, 46.2 years; range, 16-74 years). All patients had experienced recurrent angioedema, with documentation of antihistamine and/or mast cell-targeted therapy ineffectiveness and normal/near-normal laboratory data. Genetic testing (n = 9) found no known pathogenic variants of HAE. Diagnosis of HAE-nl-C1INH was confirmed in the 31 patients via a favorable response after intravenous rhC1-INH (weight-based; maximum, 4200 U) during an angioedema attack. Only 30.0% (9/30) of patients with documented information had been aware of a family history of recurrent angioedema/HAE. In conclusion, reliance on a family history of recurrent angioedema as a diagnostic criterion may delay accurate diagnosis and access to effective treatment. These results support that responsiveness to C1-INH replacement therapy may also be a useful supportive diagnostic criterion for HAE-nl-C1INH.