Credit: Adobe Stock/ Dragana Gordic
A new study identified asthma diagnoses and peanut triggers as risk factors for grade 4 anaphylaxis.1
“Our data highlight risk factors for fatal and near-fatal food anaphylaxis compared to severe anaphylaxis, notably a history of asthma and peanut as the anaphylaxis elicitor,” wrote investigators, led by Guillaume Pouessel, MD, from CH Roubaix, Department of Pediatrics at Children’s Hospital, Roubaix, France. “These high-risk individuals should benefit from personalized management strategies such as oral immunotherapy and biotherapy.”
Previous research has reported several risk factors linked to severe food anaphylaxis, including asthma, persistent cow’s milk allergy, lipid transfer protein monosensitization, prior anaphylaxis, adolescence and young adulthood, exercise, concomitant medication (non-steroidal anti-inflammatory drugs, beta-blockers, angiotensin-converting enzyme), and upright posture.2 Still, studies fail to show the impact of these factors on anaphylaxis severity. Investigators sought to assess potential risk factors for severe food anaphylaxis.2
The team retrospectively analyzed 2621 food anaphylaxis cases in the French-speaking Allergy-Vigilance Network (2002 – 2021). Using univariate and multivariate analyses, they compared characteristics of grade 4 (n = 44; 6%) vs grade 3 (n = 731; 27.9%) anaphylaxis.
Among the sample, either grade 3 or 4 cases, there were 19 deaths. Near-fatal and fatal anaphylaxis occurred in 1.7% of anaphylaxis cases in this study.
A little over half of the cases were adults (56.1%), with a mean age of 28.3 years. Despite more adult cases in the study, children had more grade 4 anaphylaxis cases (26 vs 18; P = .01).
Half of the sample was male (53.7%). Frequent triggers include peanut (13.9%), wheat (9.4%), cashew (5.8%), shrimp (5.3%), and cow’s milk (4.6%).
The most common symptoms included generalized hives (50.1%), dyspnea (33.4%), facial swelling (30.6%), bronchospasm (28.6%), and laryngeal angioedema (26.6%). Anaphylaxis mostly occurred at home (45.3%), followed by at the restaurant (12.1%), school (6.7%), and the hospital (2.3%).
The univariate analysis showed that individuals with grade 4 anaphylaxis were more likely to have a history of allergy to the food trigger (71.1% vs 42.1%; P <.001), asthma diagnosis (59.5% vs 30.4%; P <.001), and a peanut trigger (34.1% vs 12.6%; P <.001). Moreover, individuals with grade 4 were less likely to have a history of allergic rhinitis (6.8% vs 27.3%; P = .005), generalized hives (23.3% vs 51.7%; P <.001) and exercise as a cofactor (9.1% vs 23.0%; P = .049) than those with grade 3.
The multivariate analysis revealed grade 4 anaphylaxis risk factors were an asthma diagnosis (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.56 – 7.44; P = .002) and a peanut trigger (OR, 3.46; 95% CI, 1.21 – 9.34; P = .014).
Investigators also discovered differences in anaphylaxis manifestations between age groups. Not only was grade 4 anaphylaxis more common in children, but the pediatric population also had a greater prevalence of a history of food allergy to another food besides the trigger (44.4% vs 21.47%; P <.001), and atopic dermatitis (31.9% vs 5.4%; P <.001). Peanut, cashew, and cow’s milk triggers were more frequent in children (P <.001), whereas wheat (P <.001) and shrimp (P = .004) were more frequent in adults.
Furthermore, children experienced vomiting, abdominal pain, rhinitis, dyspnea, and bronchospasm more frequently than adults (P <.001). Conversely, adults had more frequent symptoms of laryngeal angioedema (P = .05) and co-factors of alcohol (P <.001) and exercise (P = .01).
“With the goal of improving clinical care and treatment, we need to go further in identifying biomarkers and analyzing endotypes, pathophysiologic pathways, and genetic factors that may be associated with an increased risk of near-fatal anaphylaxis,” investigators concluded. “This objective requires further clarification of the real impact of comorbidities, intrinsic and extrinsic cofactors in terms of severity, through larger cohort studies and international collaboration between clinicians and researchers.”
References
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Pouessel G, Egea C, Divaret-Chauveau A, et al. Risk Factors for Fatal and Near-Fatal Food Anaphylaxis: Analysis of the Allergy-Vigilance Network Database. Clin Exp Allergy. Published online May 29, 2025. doi:10.1111/cea.70089
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Turner PJ, Jerschow E, Umasunthar T, Lin R, Campbell DE, Boyle RJ. Fatal Anaphylaxis: Mortality Rate and Risk Factors. J Allergy Clin Immunol Pract. 2017;5(5):1169-1178. doi:10.1016/j.jaip.2017.06.031
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