Warning Symptoms May Foretell HAE Attacks, Study Finds

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
acquired angioedema | Angioedema News | illustration of doctors with tablet consulting

Warning symptoms, also called prodromes, may foretell where in the body and how intense an attack of hereditary angioedema (HAE) will be, a small study found.

Using input from patients, researchers observed that the majority experienced a prodrome before an attack and that almost two-thirds were able to tell when an attack was about to occur based on the prodrome.

“Patients can better cope with the challenges of the disease by using prodromes as an early warning sign and take preventative actions to mitigate attacks,” the researchers wrote. “Training patients to recognize early prodromes may be adopted as an efficient strategy for timing self-administration of rescue medication.”

Recommended Reading
A doctor holds a clipboard while consulting with a patient.

US Patients Underreport Burden of HAE to Their Doctors, Study Says

The study, “Prodromes as predictors of hereditary angioedema attacks,” was published as a letter in the journal Allergy.

In patients with HAE, a prodrome is any symptom — or series of symptoms — that precedes a swelling attack by several hours. A patient may perceive it in different ways: for example, as pain, an itch, or a feeling of anxiety, or as a skin rash or flushing. As it usually occurs more than once, it can serve as an early warning sign that preventive measures should be taken.

“Although prodromes and attacks are unpredictable and vary in their manifestations, experienced patients are more attentive to their body cues and capable of finding consistency and repetitiveness in prodromes,” the researchers wrote.

However, until recently, there was no tool to study the potential predictive value of a prodrome. To overcome this limitation, a team of researchers in Israel recently constructed and validated a new HAE-specific patient-filled questionnaire that could serve to predict the likelihood of an attack based on early warning symptoms.

“This study adds to our knowledge on prodromes and their importance as attack-predicting harbingers,” the researchers wrote.

The study included 66 patients (27 men and 39 women, with a mean age of 32.4 years). From these, 60 (90.9%) had type 1 and six (9.1%) had type 2 HAE. Most (83%) were born in Israel; the remaining were born in countries of Europe or America. Nearly all (92.4%) had a family history of the disease.

In the questionnaire, patients were asked to give an account of the prodromes and attacks experienced in the previous six months, including where they occurred in the body (in the face, the abdomen, the skin, the urinary and genital region, or the throat). The intensity of pain, severity, impairment, and functionality were rated on a visual analog scale, where a patient marks a point on a line that matches how intense a certain sensation or feeling is.

There were 223 reports of attacks, with the most common triggers being injury (69.7%) and stress (46.9%). While some patients (16.6%) did not experience a prodrome, most (83.3%) experienced a prodrome before an attack at least once, and 63.6% said they were able to predict an attack based on a prodrome.

The sensitivity of a prodrome as a predictor of an attack was 89.5%, and its specificity was 63.1%. Sensitivity is a parameter that indicates how well a test can correctly identify a certain condition — swelling attacks, in this case — whereas specificity refers to its ability to correctly identify people without the condition.

The mean intensity of a prodrome was about half — or even less — that of attacks in each of the body areas, and both were correlated. This means that more intense prodromes were associated with more intense attacks.

“Prodromes could be discriminated from attacks across all clusters [body areas], supporting our hypothesis that patients can distinguish between these two events,” the researchers wrote.

“In conclusion, we found that by using a disease-specific tool, HAE patients can distinguish prodromes from attacks and predict oncoming attacks,” they wrote, adding that “personal experience is a crucial factor in the patients’ perception of a prodrome and ability to respond.”