The US HAEA Scientific Registry: Triggers and Prodromes.

BACKGROUND

Triggers and prodromes have been reported as preludes to hereditary angioedema (HAE) attacks.

OBJECTIVE

Utilizing data from the US HAE Association Scientific Registry, we describe the clinical characteristics of triggers, prodromes, and their relationships to attack onset.

METHODS

Clinical data concerning trigger and prodrome types, frequency, and the likelihood of having a subsequent attack were extracted from the Scientific Registry. Data were compiled from both HAE-C1INH and angioedema non-mast cell-mediated with normal C1INH (ANM-nl-C1INH) cohorts.

RESULTS

HAE-C1INH cohort: 458 of 485 subjects recorded triggers with stress the most frequent (91.5%) followed by minor trauma (83.2%) and infection (67.3%). Hormonal triggers were the most likely to always be followed by an attack. Prodromal symptoms were reported by 399 (82.3%) with the most frequent being non-itchy rash (78.7%), sense/hunch (52.6%), tiredness/fatigue (47.2%) and tightness/prickling (45.8%). A prodromal sense/hunch of an impending attack was the most likely to always be followed by an attack (47.4%). ANM-NL-C1INH COHORT: 83 of 96 subjects documented 1 or more triggers with stress the most common (81.25%) and menses the most likely to always be followed by an attack (38.5%). Prodromal symptoms were reported in 83 with the most common being tightness/prickling (58.3%), tiredness/fatigue (56.3%), non-itchy rash (51.0%), and a sense/hunch (45.8%). The prodrome that had the highest percentage of always being followed by an attack was a tightness/prickling sensation (62.2%).

CONCLUSION

Our analysis highlighted the importance of stress and hormonal attack triggers. The sense/hunch of an impending attack was the most reliable prodrome for HAE-C1INH vs tightness/prickling in ANM-nl-C1INH. Erythema marginatum type eruptions were common in all subjects. We hypothesize that triggers and prodromes are fundamentally interconnected with attacks of HAE through activation of kinin generating pathways.