Identifying High‑Risk Patients and Recognizing Anaphylaxis in Infants

Not all patients with anaphylaxis share the same risk of severe or refractory reactions, and primary care clinicians should be familiar with key clinical and comorbid features that heighten concern. Prior severe anaphylaxis, previous need for multiple doses of epinephrine, and a history of hospitalization for anaphylaxis are strong predictors of future severe events. Uncontrolled asthma is a particularly important modifiable risk factor repeatedly associated with worse respiratory outcomes across different triggers, including foods and venoms. Additional “augmentation” or co‑factors—such as physical exertion, emotional stress, alcohol intake, use of β‑blockers or angiotensin‑converting enzyme inhibitors, and nonsteroidal anti‑inflammatory drugs—may lower the threshold for anaphylaxis or intensify its severity.

In adult venom allergy, underlying clonal mast cell disorders clearly increase the risk for severe reactions, whereas the role of hereditary α‑tryptasemia remains under study. For food allergy, certain allergens such as peanut and tree nuts (for example, cashew) are frequently implicated in severe reactions, although cohort findings vary. Regardless of trigger, comprehensive risk assessment should consider comorbid lung disease, cardiovascular medications, prior reaction history, and environmental or behavioral co‑factors. This risk stratification informs both the strength of recommendations for epinephrine carriage and the intensity of counseling around early use and emergency evaluation.

Infants and toddlers present an additional challenge because they cannot verbalize key symptoms such as throat tightness or impending airway compromise. In this video discussion, Golden and Lieberman describe how behavioral cues—unusual or inconsolable fussiness, lethargy, changes in appearance, tongue thrusting, ear pulling, repetitive rubbing of the face or mouth, and vomiting—may serve as proxies for pruritus or discomfort after allergen exposure. The faculty note that early food introduction guidelines are increasing the number of observed reactions in infancy, most of which are mild, but some meet criteria for anaphylaxis. They recommend applying existing diagnostic criteria while reasonably incorporating infant‑specific signs, and they stress that treatment principles are the same across age groups: intramuscular epinephrine should be given promptly using available pediatric doses, even in very young or low‑weight infants, rather than withheld out of concern for “overdosing.”

Disclosures include Novartis Pharmaceuticals, Regeneron Pharmaceuticals, BioCryst, GlaxoSmithKline, Amgen, GENZYME Corporation, AstraZeneca Pharmaceuticals, and LEO Pharma for Schroer; Novartis Pharmaceuticals, ABBVIE, Genentech, Aquestive Therapeutics for Lieberman; and Phadia US and Genentech USA for Golden.

References:

1. Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124-176. doi:10.1016/j.anai.2023.09.015

2. ARS Pharma. ARS Pharmaceuticals Announces FDA Approval of neffy® 1 mg (epinephrine nasal spray) for Type I Allergic Reactions, Including Anaphylaxis, in Pediatric Patients Weighing 15 to < 30 Kilograms - ARS Pharmaceuticals. ARS Pharmaceuticals. Published March 5, 2025. Accessed February 20, 2026. https://ir.ars-pharma.com/news-releases/news-release-details/ars-pharmaceuticals-announces-fda-approval-neffyr-1-mg

3. Aquestive Therapeutics. Aquestive Therapeutics Announces FDA Issuance of Complete Response Letter for Anaphylm^TM - Aquestive Therapeutics. Aquestive Therapeutics. Published February 6, 2026. Accessed February 20, 2026. https://investors.aquestive.com/news-releases/news-release-details/aquestive-therapeutics-announces-fda-issuance-complete-response