Guidelines for diagnosing hereditary angioedema (HAE) with normal C1 esterase inhibitor (NC1-INH), an extremely rare HAE subtype, require further implementation in clinical practice, suggests a multicenter chart review study published in the Annals of Allergy, Asthma & Immunology.

Although the study has demonstrated that real-world NC1-INH-HAE diagnosis is generally aligned with US guidelines, some diagnostic criteria, including genetic testing and family history, were less represented in patient charts.

Expert HAE clinicians endorsed 4 of 6 diagnostic criteria. Of those, 3 were well represented in patient charts (92%-100%). Family history was only represented in 25% of patient charts. The 2 diagnostic criteria with lower expert endorsement (50% and 75%) were found in 8% and 100% of patients charts, respectively.


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According to the study, the top 3 previous misdiagnoses were irritable bowel syndrome (67%), other gastrointestinal disorders (71%), and anaphylaxis (54%).

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Moreover, patients on prophylaxis prior to the index date had a monthly attack rate of 5.60 at baseline, which decreased to 2.41 at 7 to 12 months after the initiation of lanadelumab treatment.

The authors interviewed 4 expert HAE clinicians regarding their clinical experience in diagnosing NC1-INH-HAE. Three of them completed a case report form using data from patient records. Twenty-four lanadelumab-treated patients (mean age, 44 years; 92% female; median years between symptom onset and diagnosis, 5) from 3 centers in the United States were included in the study.

NC1-INH-HAE, also known as type 3 HAE, is more frequently observed in women. Recent studies suggest that increased estrogen levels and a gain-of-function mutation in the gene coding for factor XII could be associated with type 3 HAE. Currently, there are no diagnostic assessments or phase 3 trial data for NC1-INH-HAE.

Reference

Bernstein J, Kanarek H, Soteres D, et al. Diagnostic pathways in lanadelumab-treated patients with normal C1-inhibitor hereditary angioedema (NC1-INH-HAE): a multicenter chart review. Ann Allergy Asthma Immunol. 2022;129(5):S29. doi:10.1016/j.anai.2022.08.587