Background/Objectives: Current management of Hereditary Angioedema (HAE) predominantly focuses on acute attack control and prophylaxis. However, the cumulative “inter-attack” burden driven by chronic low-grade inflammation and its impact on physical frailty remain under-investigated. This preliminary, proof-of-concept study proposes a novel composite score, the “Hereditary Angioedema Frailty and Inflammation Score” (HAE-FIS), to quantify this inter-attack frailty-like inflammatory burden. Methods: In this single-center retrospective study, 46 patients with C1-inhibitor deficiency were evaluated. The HAE-FIS (range 0–5) was constructed using five routinely available biomarkers reflecting inflammation and nutritional status: C-reactive protein (CRP), albumin, hemoglobin, body mass index (BMI), and inter-attack symptom burden. Patients were categorized based on annual attack frequency (Infrequent ≤ 6 vs. Frequent > 6 attacks/year). Results: The median diagnostic delay was 12.0 years. Patients with frequent attacks had significantly higher median HAE-FIS scores compared to the infrequent group (p = 0.008). Component analysis revealed that ‘High CRP’ (46.4% vs. 16.7%; p = 0.039) and ‘Low BMI’ (25.0% vs. 0.0%; p = 0.032) were significantly more prevalent in patients with frequent attacks. Notably, low BMI was observed exclusively in the frequent attack group, suggesting a specific phenotype at risk for sarcopenia. While multivariable logistic regression was constrained by the sample size, the annual attack count emerged as the strongest predictor for a high HAE-FIS score (OR: 1.049; p = 0.070). Conclusions: High attack frequency in HAE is associated with a measurable cumulative systemic burden characterized by inflammation and nutritional risk. These findings support the development of an “HAE Rehabilitation” framework integrating functional preservation into long-term management.
Gerek et al. (Wed,) studied this question.