Infectious Disease

Tree nut oral immunotherapy deemed safe, tolerable for preschoolers

April 04, 2023

3 min read


Erdle reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.


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Key takeaways:

  • 95.6% of the patients reached maintenance therapy.
  • During the buildup phase, 38% had grade 1 reactions and 32.6% had grade 2 reactions.
  • Two patients received epinephrine during therapy.

OIT for tree nut allergies was safe and tolerable among a preschool population with results comparable to OIT for peanut allergy, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

Considering these results, tree nut OIT should be offered as an alternative to strict avoidance, Stephanie C. Erdle, MD, FRCPC, investigator and allergist, division of allergy and immunology, department of pediatrics, University of British Columbia, BC Children’s Hospital, and colleagues wrote.

The safety profile of oral immunotherapy for tree nut allergies among preschoolers was comparable to peanut oral immunotherapy. Image: Adobe Stock

The study involved 92 children (median age, 35 months; interquartile range [IQR], 23-53 months; 65.2% boys) enrolled in tree nut OIT as part of the Food Allergy Immunotherapy registry at four community and academic allergy clinics in Canada between August 2018 and April 2021.

These patients included 79 (85.9%) with a single tree nut allergy, including cashew (n = 58), walnut (n = 19), hazelnut (n = 1) and macadamia (n = 1). Also, 13 (14.1%) had allergies to multiple tree nuts, including 10.8% with allergies to two tree nuts and 3.3% with allergies to three tree nuts, including combinations of cashew, walnut, hazelnut and almond.

Additionally, 88 (95.7%) had histories or reactions to at least one tree nut, including 35 (38%) grade 1 reactions, 49 (53.3%) grade 2 reactions, no grade 3 reactions and four (4.3%) grade 4 reactions .

Nineteen (20.7%) of the patients had a baseline oral food challenge. Also at baseline, median tree nut specific IgE level was 4.02 kU/L (IQR, 1.14-9.61) and skin prick test wheal diameter was 8 mm (IQR, 6 mm-10 mm). Doses were escalated every 2 weeks for 37 (40.2%) of the patients, every 2 to 4 weeks for 44 (47.8%) and every 4 weeks for 11 (12%).

Four patients (4.3%) dropped out of treatment, and 88 (95.6%) reached maintenance. Three of those who dropped out were on OIT for cashew allergy, and the fourth was on OIT for walnut and cashew allergy.

One of these patients dropped out due to moving. The other three dropped out for symptom-related reasons, including one due to abdominal pain and another who experienced delayed vomiting after dosing, which the researchers said could be consistent with eosinophilic esophagitis such as OIT-related syndrome.

During the buildup phase, 70.6% experienced symptoms, including 35 (38%) who experienced grade 1 reactions and 30 (32.6%) who experienced grade 2 reactions, with no grade 3 or 4 reactions.

Among patients treated for one tree nut allergy, 53 (67%) had grade 1 reactions and 25 (31.6%) had grade 2 reactions, and 53% of these grade 2 reactions were isolated gastrointestinal symptoms such as abdominal cramps, vomiting or diarrhea that did not require treatment.

Physicians considered 26.7% of the remaining grade 2 reactions to be mild reactions that did not require epinephrine. However, the physicians said they would have recommended epinephrine for 20% of these remaining reactions.

Two patients (2.53%) receiving OIT for single tree nut allergies received epinephrine for their grade 2 reactions. One of them (1.27%) went to the ED. Four patients who should have received epinephrine based on the physicians’ recommendations did not.

The researchers reported that these patients all received education about the importance of epinephrine after these reactions and before they continued with OIT.

The patients treated for multiple tree nut allergies included seven (53.8%) with grade 1 reactions and six (46.2%) with grade 2 reactions. None of the patients treated for multiple allergies received epinephrine or went to the ED.

The researchers did not report any significant differences in frequency or grade of reaction based on the timing of the dose escalations. Also, none of the patients were diagnosed with EoE during buildup.

According to the researchers, these findings were consistent with their previous research in peanut OIT, which found 67.8% of patients experiencing symptoms, 4.07% receiving epinephrine, 0.37% diagnosed with EoE and 10% dropping out during buildup.

The researchers expressed confidence that the safety profile for tree nut OIT for a preschool population was comparable to the safety profile for peanut OIT in this age group, which is now common, and that physicians should not hesitate to offer it.

Similarly, the researchers expect the effectiveness of OIT for tree nut allergy to be comparable to peanut OIT as well. Next, the researchers said they will continue to examine the safety and tolerance of tree nut OIT as well as its effectiveness based on follow-up OFCs and its impact on quality of life in this age group.



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Matthew Greenhawt, MD, MBA, MSc)

Matthew Greenhawt, MD, MSc, FACAAI

These are not surprising findings and compare similarly with the experience at my center. Real-world studies like this are highly important to show how concepts can be translated to the typical outpatient setting. Centers like ours have many preschool-aged tree-nut allergic individuals whose families are very interested in OIT, and this study demonstrates that this can be done safely and effectively, as is similar to our center’s experience.

Matthew Greenhawt, MD, MSc, FACAAI

Director of the Food Challenge and Research Unit, Children’s Hospital Colorado

Disclosures: Greenhawt reports having advisory board membership with Aquestive Therapeutics.


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