Management of hereditary angioedema with normal C1Inh: a series of 163 French patients.

BACKGROUND: The diagnosis of hereditary angioedema with a normal C1Inh was genetic. The two most frequent pathogenic variants are found in the FXII and PLG genes. Their management is similar to that of HAE patients with C1Inh deficiency but without evidence-based medicine. OBJECTIVE: The French Reference Centre for Angioedema (CREAK) Our center identified all patients with HAE with a normal C1Inh to evaluate their therapeutic management. METHODS: This was a national retrospective study conducted in our center the CREAK network. RESULTS: A total of 287 patients were identified with an F12 pathogenic variant (133 families), 38 with PLG (12 families) and one patient with KNG1. Among these patients, 111 patients with HAE-FXII and 19 patients with HAE-PLG were symptomatic. More women than men were symptomatic (86.3% vs. 30.8%, respectively) (p < 0,0001). The mean age at first attack was 24 ± 12 years. 49% of patients with HAE-FXII were estrogen dependent (vs. 0% HAE-PLG, p < 0,01). 91% of patients with HAE-PLG needed to receive at least one attack of icatibant with 100% efficacy. 67% of patients with HAE-FXII were treated at least once: 56% with icatibant and 54% with C1Inh concentrate (during pregnancy). 12,6% of patients with HAE-FXII and 47,4% of patients with HAE-PLG required long-term prophylactic treatment: 66,7% of patients HAE-PLG who were taking tranexamic acid were attack-free (vs. 37,5 3% of HAE-FXII patients). 100% of patients with HAE-FXII treated with lanadelumab were completely asymptomatic (vs. 25% of patients with HAE-PLG). CONCLUSION: HAE patients with a normal C1inh have specific clinical features, including a later age at first attack than HAE patients with a normal C1inh, high sensitivity to estrogens of HAE-FXII and the location of the HAE-PLG on the tongue. The treatments used for HAE patients with C1Inh deficiency appear to be effective and safe. Low-dose progestin-only pills are good contraceptive options.