Stress led all triggers, and a sense of an impending attack was the most reliable prodrome in patients with HAE-C1INH in the US HAEA Scientific Registry.
Stress was the most common trigger of
The analysis examined trigger and prodrome types, frequency, and their relationship to attack onset.¹ Data came from 2 cohorts: patients with HAE due to C1 inhibitor deficiency (HAE-C1INH) and patients with angioedema non-mast cell-mediated with normal C1 inhibitor (ANM-nl-C1INH).¹ Prospective prodrome data have been limited; in 1 prior survey of 21 patients reporting on 253 treated attacks, prodromes preceded 67.6% (171/253) of attacks, with a median lead time of 12 hours.²
"Our analysis highlighted the importance of stress and hormonal attack triggers," wrote Sandra C. Christiansen, MD, of the Department of Medicine at the University of California San Diego, and colleagues.
Of 485 participants in the HAE-C1INH cohort, 458 recorded ≥ 1 trigger.¹ Stress was the most frequently reported trigger (91.5%), followed by minor trauma (83.2%) and infection (67.3%).¹ Hormonal triggers were the most likely to always be followed by an attack.¹
Prodromal symptoms were reported by 399 of 485 participants (82.3%).¹ The most frequent prodrome was a non-itchy rash (78.7%), followed by a sense or hunch of an impending attack (52.6%), tiredness or fatigue (47.2%), and a tightness or prickling sensation (45.8%).¹
Although less common than rash, the sense or hunch carried the strongest link to a subsequent attack. It was the prodrome most likely to always be followed by an attack (47.4%).¹ Erythema marginatum-type eruptions were common across all participants, according to the investigators.¹
In the ANM-nl-C1INH cohort, 83 of 96 participants documented ≥ 1 trigger.¹ Stress was again the most common trigger (81.25%), and menses was the trigger most likely to always be followed by an attack (38.5%).¹
Prodromal symptoms were reported by 83 of 96 participants.¹ Tightness or prickling was the most common prodrome (58.3%), followed by tiredness or fatigue (56.3%), non-itchy rash (51.0%), and a sense or hunch of an impending attack (45.8%).¹
In contrast with the HAE-C1INH cohort, the most reliable prodrome in this group was a tightness or prickling sensation, which had the greatest likelihood of always being followed by an attack (62.2%).¹ Across both cohorts, stress led all reported triggers, and hormonal factors showed the strongest association with subsequent attacks.¹
The findings extend prior work suggesting prodromes often occur early enough to allow on-demand treatment to begin before swelling develops.² The registry data point to a patient-reported sense of an impending attack in HAE-C1INH, and tightness or prickling in ANM-nl-C1INH as the prodromes most consistently tied to attack onset.¹
“We hypothesize that triggers and prodromes are fundamentally interconnected with attacks of HAE through activation of kinin generating pathways,” investigators concluded.
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