Sandra C Christiansen, Joyce Wilmot, Christine Selva, Sherry Swanson, Anthony J Castaldo, Bruce L Zuraw, US HAEA Medical Advisory Board members
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.
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.