Per-attack reporting of prodromal symptoms concurrent with C1-inhibitor treatment of hereditary angioedema attacks

Prodromal symptoms commonly precede hereditary angioedema (HAE) attacks. There is continuing interest in evaluating prodromes as treatment indicators, but a paucity of relevant data. This study was designed to prospectively identify prodomal characteristics in patients voluntarily reporting such information around the time of seeking treatment for an acute HAE attack.

Twenty-eight patients with HAE were enrolled in this survey, which was conducted in the context of an open-label study of treatment of HAE attacks with plasma-derived C1-inhibitor concentrate. At the time of treatment, patients were encouraged to answer survey questions about prodromal symptoms preceding that particular HAE attack.

Twenty-one patients provided prodromal information for 253 treated HAE attacks. Seventy-one percent of patients (15/21) reported prodromes. Three patients accounted for approximately 80% of the attacks and 89% of the reported prodromal symptoms. Prodromes were experienced before 67.6% (171/253) of attacks, with a mean of 1.4 prodromes per attack. Fatigue was the most frequent prodrome (42% of attacks), followed by nausea (26%), and flu-like symptoms (22%). The median duration of a prodrome before an attack was 12 h (range, 0.33-24 h).

Despite many limitations in the study design, these findings confirm that prodromes are frequently associated with HAE attacks in many patients and occur sufficiently early to allow time for treatment initiation. The frequency of "false positive" prodromal symptoms remains undetermined, and the authors captured data only on attacks severe enough to warrant treatment. Additional well-designed prospective studies are clearly needed to continue investigating the potential clinical relevance of prodromes.