High-grade reactions requiring epinephrine rare during at-home oral immunotherapy
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Key takeaways:
- The researchers identified 390 reactions requiring epinephrine during 1,637 cases of home administration of oral immunotherapy.
- These incidents included 30 high-grade reactions occurring during 27 treatments.
Severe reactions during home oral immunotherapy were rare, and milk OIT, asthma and sensitization to house dust mite were the main risk factors, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Providers should discuss these possible outcomes with patients who meet these risk profiles, Liat Nachshon, MD, fellow at the Institute of Allergy, Immunology, and Pediatric Pulmonology, Yitzhak Shamir Medical Center, and colleagues wrote.
The single-center study examined 1,637 courses of OIT for food allergy among children aged 3.5 years and older completed between April 2010 and January 2020, including 880 for milk, 346 for peanut, 221 for tree nuts, 115 for sesame and 75 for egg.
These courses involved 1,327 patients who had a single treatment, 123 who had two consecutive treatments, 16 with three consecutive treatments and four with four consecutive treatments.
The researchers counted 252 treatments where there were reactions addressed with epinephrine at home during the 1,637 courses (15.4%). The 390 reactions that the researchers analyzed included 268 from milk, 10 from egg, 57 from peanut, nine from sesame and 46 from tree nuts.
Also, 166 of these treatments involved a single reaction, 53 involved two reactions, 25 involved three reactions, seven involved four reactions and three involved five reactions.
The researchers noted that the reports on about 50 of the 390 reactions they analyzed only indicated that epinephrine was administered with prompt resolution with no further details. The respiratory system was involved in 90.9% of the remaining 340 reactions, and multisystem reactions classified as anaphylaxis occurred in 266 reactions.
Patients received a single dose of epinephrine in 349 (98.5%) of these cases and more than one dose in 41 (2.5% of all treatments) of these cases. Also, 239 were admitted to a local ED, whereas the remaining patients experienced prompt resolution of their symptoms.
There were 27 patients who were hospitalized, including 11 classified as high-grade anaphylaxis, with reactions associated with vital sign impairment and meeting the criteria for Delphi grade V or Consortium for Food Allergy Research grade IV/severe grade III.
Among the 381 patients who reported where they received their first epinephrine dose, 332 (87.1%) received them at home, including three patients who received their dose from EMS personnel. Nine patients received their first dose in a community clinic, and 37 received it in the ED.
The researchers further tallied 30 high-grade reactions during 27 treatments, or 1.65% of all OIT treatments, including 26 during OIT for milk (2.95% of all milk treatments), two during peanut treatment (0.58%), one during sesame treatment (0.87%) and one during tree nut treatment (0.45%).
Also, 26 of these high-grade reactions were among patients who were sensitized to house dust mite, and 26 of them were among patients who had asthma. However, the researchers determined that only one of these reactions was triggered by asthma exacerbations.
The researchers additionally noted that 21 of these high-grade reactions were not preceded by a previous non-high-grade reaction during treatment and could not have been anticipated.
The median duration between the beginning of treatment and when the high-grade reaction occurred was 150 days (interquartile range [IQR], 60-343 days; range, 4-1,164 days). The interval from recent updosing was 16 days (IQR, 9-28 days; range, 1-136 days).
High-grade reactions occurred throughout the span of doses, which ranged from 2.5 mg to 7,200 mg of protein, but mostly occurred following doses of less than 500 mg for all the allergens treated.
In addition to the case caused by an asthma exacerbation, triggers behind these high-grade reactions included exercise (n = 4), fatigue (n = 5), concurrent illness (n = 3), hot showers shortly after doses (n = 2) and menstruation (n = 1). However, the researchers could not identify a trigger for 14 of these reactions.
Milk treatment accounted for 85.2% of the high-grade reactions and 64.4% of the reactions that were not high grade. Patients with high-grade reactions also were more likely to have asthma and house dust mite sensitization (P = .02 for both).
After multivariable stepwise logic regression, milk OIT (adjusted OR = 3.3; 95% CI, 1.09-10.03) and sensitization to house dust mite (aOR = 5.5; 95% CI, 1.26-24.3) remained significant predictors for high-grade reactions.
The researchers did not find any significant differences in prevalence of exercise, disease, fatigue or other augmenting factors between the high-grade reactions and the reactions that were not high grade, with 40% of reactions in both groups attributed to unidentified triggers.
Rates of treatment failure included 52% for the patients with high-grade reactions and 26% for those who did not have high-grade reactions (P = .022), although the high-grade group included 26% who eventually were fully desensitized and 22% who were partially desensitized. The four patients who had high-grade reactions to foods other than milk were fully desensitized as well.
The nine cases of refractory anaphylaxis (0.55% of all OIT treatments), where the reaction did not respond to a second dose of epinephrine, all involved patients on milk OIT with asthma and sensitization to house dust mite.
The researchers called OIT for milk the most prominent risk factor for high-grade reactions, with associations with the most severe reactions. Also, they called sensitization to house dust mite a significant predictor for high-grade reactions, but they added that the role of asthma remains controversial.
Considering these risks, the researchers encouraged providers to discuss these reactions with patients who are considering OIT for food allergies, especially with those with asthma, house dust mite sensitization and milk allergy.
Perspective
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Aikaterini (Katherine) Anagnostou, MD (Hons), MSc, PhD
This is really interesting work, providing insight into OIT-related, severe, at-home reactions during the updosing phase. As expected, severe allergic reactions during therapy are uncommon, with refractory anaphylaxis even less so. This finding highlights the importance of educating patients on both consistent carriage of epinephrine and prompt use in case of severe allergic reactions. A key takeaway from the study is that, for reasons we do not yet understand, milk OIT appears to place patients more at risk for severe reactions compared with other OIT foods. More research is needed in this area, ideally from multiple centers around the world to further examine these findings.
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