Body stress signals in HAE match those of autoimmune disorder ITP
Data suggest physical response to stress may be universal in chronic illness
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Adults with hereditary angioedema (HAE) experience physical stress responses similar to those with other chronic conditions, such as the autoimmune condition immune thrombocytopenia (ITP), in which stress is usually not involved in disease flare-ups.
A new study found that when faced with stressful tasks, HAE patients showed heart rate and skin conductance changes nearly identical to those of patients with ITP, a condition in which the immune system mistakenly attacks platelets, or the cell fragments that help blood clot. These findings suggest that the way the body physically processes emotion in chronic illness may be more universal than previously thought.
“These results shed new light on the role of emotional regulation in chronic diseases,” researchers wrote in the study “Physiological evaluation of the emotional regulation of patients with hereditary angioedema,” which was published in BioPsychoSocial Medicine.
The cycle of stress and swelling
HAE is an inherited disease characterized by recurrent episodes of swelling that typically self-resolve, separated by periods of remission. Swelling attacks may affect the face, respiratory tract, extremities, and abdomen.
Triggers of HAE attacks can include trauma, viral infections, medical and dental procedures, hormonal fluctuations, allergens, and physical activity.
Patients also report that emotions, particularly emotional stress, can trigger HAE attacks. Everyday stressors include anxiety, fear of future attacks, major life changes, and daily pressures, creating a cycle where stress induces swelling, which causes further distress.
While stress can be assessed using self-reported questionnaires, it can also be measured physiologically through changes in heart rate and electrodermal activity, as well as variations in the electrical properties of the skin in response to sweat gland activity. These responses are mediated by the autonomic nervous system, which regulates involuntary processes such as heart rate, blood pressure, breathing, and digestion.
In this study, a French research team used physiological measures to investigate stress regulation in 13 people with HAE.
As a comparison, they also assessed 13 age- and sex-matched adults with ITP. This autoimmune condition is also characterized by flare-ups, typically triggered by infections, certain medications, or other autoimmune diseases, rather than by emotional stress.
Among HAE patients, stress was the most common attack trigger (85%), followed by physical activity (62%) and physical trauma (54%). Most HAE patients were receiving Takhzyro (lanadelumab), while one was treated with Orladeyo (berotralstat). Over the previous six months, HAE patients experienced twice as many attacks on average as ITP patients (5.27 vs. 2.23).
To assess the physiological stress response, participants wore a specialized wireless wristband that continuously collected heart rate and electrodermal activity data in real time.
Responses were measured at rest and during three computer-based tasks to invoke stress: reactivity, breathing, and cognitive function. The reactivity task involved pressing a key as soon as a marker appeared on the screen, the breathing task involved short inhalations followed by long exhalations, and the cognitive task involved a mathematical problem.
Understanding the burden of chronic illness
The analysis found no significant differences between HAE and ITP patients in heart rate variability or in electrodermal activity with respect to emotional activation or the strength and duration of the stress response across all three tasks.
Among HAE patients, no differences in stress responses were observed between men and women, except for a correlation between physician-perceived patient stress and the number of measured emotional reactions in women alone. Even so, this difference was not statistically significant, meaning it could have arisen by chance.
Likewise, HAE treatment did not affect any stress responses triggered by the reactivity, breathing, and cognitive function tasks.
“Although ITP attacks are usually not emotionally-triggered, patients remain burdened with living with a chronic, attack-prone and potentially fatal rare condition, which may have biased our results and neutralized significant differences between the disease groups,” the team noted.
“As such, it would be interesting to account for this potential bias by including a ‘healthy control’ group or by comparing HAE and ITP with and without anxiety-depressive disorders,” they added.
