IntroductionHereditary Angioedema due to C1-INH deficiency (HAE-C1INH) is a rare genetic condition associated with poor quality of life (QoL). Affect, defined by Activation (energy) and Valence (pleasantness), is linked to QoL and fluctuates daily, reflecting emotion regulation processes. This study explored affective dynamics in HAE-C1INH patients, with (HAE A+) and without attacks (HAE A−), comparing them to healthy controls (CTR), using Ecological Momentary Assessment (EMA). Secondarily, correlation between affective dynamics and Angioedema Quality of Life (AE-QoL) was assessed.MethodsIn this observational study, 12 HAE-C1INH patients and 14 CTR completed weekly EMA surveys over 16 weeks, assessing Positive Activation (PA), Negative Activation (NA), and Valence (VA). Affective intensity, variability, and instability were computed. HAE-C1INH participants also completed two self-administered questionnaires: AE-QoL and Angioedema Control Test (AECT) assessing QoL and disease control, respectively.ResultsPatients showed higher mean VA (p = 0.016) and lower NA for worry (p = 0.021) than CTR. HAE A− had higher PA and VA, and lower NA for anger and worry than both HAE A+ and CTR. AE-QoL correlated negatively with PA (r = −0.78, p = 0.003) and VA (r = −0.68, p = 0.014).ConclusionPatients, especially those without attacks, displayed more positive emotional profiles than controls. EMA captured emotional patterns not evident in traditional questionnaires, supporting its value as a complementary tool for QoL evaluation in rare chronic diseases.