Researchers in Israel have discovered that prodromes can predict edema attacks in patients with hereditary angioedema, according to a study published on Authorea Preprints.

Prodromes are premonitory signs and symptoms that precede an attack. This term is most commonly used to describe the warning signs and symptoms preceding a migraine headache. However, for more than a century, scientists have known that patients with hereditary angioedema can have prodromal symptoms.

“Recent data suggests that a large majority of [hereditary angioedema] patients experience portending perceptions prior to full-blown attacks, and many claim that they are able to predict oncoming attacks by having a prodrome,” the authors of the study wrote. 

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The researchers hence conducted a prospective study on the link between prodromes and attacks in patients with hereditary angioedema. They recruited 48 patients from 4 academic centers in Israel. Patients with low functional C1-esterase inhibitor (C1-INH) levels and normal C4 levels were excluded. 

Read more about hereditary angioedema etiology 

Participants were asked to report on prodromal symptoms that led to an attack, using questionnaires in real time. They were also asked to report on attacks without prodromal symptoms, as well as prodromal symptoms that did not lead to an attack. Researchers then analyzed the body locations of these prodromes and attacks, as well as their severity. 

The researchers discovered that prodromes in the abdomen and extremities were more severe than those that occurred in other locations, such as the face, oropharynx, or urogenital areas. Likewise, attacks in the abdomen and extremities were more severe and intense than those in other anatomical locations. It is important to note that perceptions of prodromal symptoms are personal and hence subjective. 

“We found in all indicated body domains (clusters) that experiencing a prodrome increases the risk of having an attack in the same location,” the authors wrote. “These findings support our basic theory regarding the utility of prodromes as predictors of oncoming attacks.” 


Reshef A, Leibovich-Nassi I, Golander H. Prodromes predict attacks of hereditary angioedema: results of a prospective study. Authorea Preprints. Published online August 12, 2022. doi:10.22541/au.166028589.91246003/v1