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Updated: May 28, 2026

Intralymphatic Immunotherapy and Vaccination in Mice
Published on: February 2, 2014
Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections: ACAAI/AAAAI surveillance
Tolly G Epstein1, Gary M Liss, Karen Murphy-Berendts
1Department of Medicine, Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Ohio, USA. epsteite@uc.edu
Background:
Incidences of subcutaneous immunotherapy (SCIT) related systemic reactions (SRs) and fatal reactions (FRs) are not well defined, nor are delayed-onset SRs and their treatment.
Objectives:
To estimate SCIT-related SRs/FRs, and the incidence and treatment of delayed-onset SRs.
Methods:
In 2008 and 2009, American Academy of Allergy, Asthma & Immunology (AAAAI) and American College of Allergy Asthma & Immunology (ACAAI) members completed a survey about SCIT-related SR severity (grade 1 = mild; grade 2 = moderate; grade 3 = severe anaphylaxis). In 2009, members reported the time of onset and use of epinephrine (EPI), with early onset defined as beginning ≤30 minutes, and delayed onset beginning more than 30 minutes after injections.
Results:
As in year 1, no FRs were reported during year 2 (630 total practices responded). Among 267 practices providing data on the timing of SRs, 1,816 early-onset SRs (86%) and 289 (14%) delayed-onset SRs were reported. Fifteen percent (226/1,519) of grade 1, 10% (54/538) of grade 2, and 12.5% (9/72) of grade 3 SRs were delayed-onset. Among early-onset SRs, EPI was given for 71% of grade 1, 93% of grade 2, and 94% of grade 3s. Among delayed-onset SRs, EPI was given for 56% of grade 1, 67% of grade 2, and 100% of grade 3s (P = .0008 for difference in EPI administration based on severity; P = .07 based on time of onset).
Conclusions:
Delayed-onset SRs are less frequent than previously reported. Epinephrine was given less frequently for grades 1 and 2 (but not grade 3) delayed-onset SRs compared with early-onset SRs. Further study of prescribing self-injectable EPI for SCIT patients in the event of delayed-onset SRs may be warranted.
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