Oral immunotherapy for hazelnut allergy does not yield other tree nut desensitization
Key takeaways:
- 96.7% of the treatment group and 14.3% of the control group achieved desensitization to hazelnut.
- Most patients who also had walnut and cashew allergy did not see any changes in those reaction thresholds.
Hazelnut oral immunotherapy was safe and effective, but cross-desensitization for patients who also had walnut and cashew allergy was unlikely, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Patients with these other allergies should treat them before treating their hazelnut allergy, Arnon Elizur, MD, director, Institute of Allergy, Immunology and Pediatric Pulmonology, Yitzhak Shamir Medical Center, and colleagues wrote.
“First, we wished to examine whether hazelnut OIT is as effective and safe as OIT to other nuts,” Elizur told Healio. “Second, our goal is to minimize the number of treatments patients with tree nut allergy need to undergo, and the number/amount of food allergens they are required to consume long-term, to improve compliance.”
Previously, the researchers showed that treating patients who were allergic to both hazelnut and walnut for walnut also would cross-desensitize approximately 65% of them to hazelnut.
“We wanted to learn whether it would work in the opposite direction as well,” Elizur said.
The prospective observational study included 30 patients aged 4 years and older (median age, 9.7 years; 63.3% male) with an IgE-mediated hazelnut allergy (eliciting dose, 120 mg of hazelnut protein) who received hazelnut OIT.
Also, 14 patients (median, 9.3 years; 50% male) with a hazelnut allergy who were evaluated for tree nut OIT but who were not treated served as controls. The treatment and control groups had comparable rates of hazelnut sensitization, the researchers said.
Twenty-nine patients in the treatment group (96.7%) and two patients in the control group (14.3%) achieved desensitization to 4,000 mg of hazelnut protein (OR = 25.7; 95% CI, 3.7-178.7).
One patient in the treatment group stopped treatment after experiencing abdominal and chest pain immediately after taking the first dose.
Ten patients in the treatment group were up-dosed monthly to the maximum dose of 4,000 mg and were then instructed to consume a monthly dose of 1,200 mg of hazelnut protein daily at home. They returned at least 6 months later and passed an oral food challenge for 4,000 mg.
The other 19 patients were up-dosed monthly to a dose of 1,200 mg of hazelnut, which they consumed daily at home for more than 6 months. At that point, they underwent a 4,000 mg OFC, which they all passed.
Hazelnut skin prick test results fell from 9 mm to 5 mm (P = .003) and specific IgE fell from 7 kUA/L to 3 kUA/L (P = .001) with clinical desensitization. Also, hazelnut specific IgG4 increased from 0.8 mgA/L to 2.6 mgA/L (P = .009).
Specific IgE levels for hazelnut components also fell, including decreases from 1.6 kUA/L to 0.7 kUA/L (P = .009) for Cor a 9, from 6.6 kUA/L to 1.6 kUA/L (P = .001) for Cor a 14, and from 2 kUA/L to 0.8 kUA/L (P = .017) for Cor a 16.
Specific IgG4 levels increased from 0.3 mgA/L to 0.7 mgA/L (P = .03) for Cor a 9 and from 0.1 mgA/L to 2 mgA/L (P = .03) for Cor a 14.
During the in-clinic up-dosing, 21 patients (70%) had reactions to 4.3% of the doses, which the researchers classified as mild (grade 1 or 2). Four patients (13.3%) received injectable epinephrine.
During the at-home dosing, 19 patients (63.3%) had reactions to 1% of the doses. Most of these reactions were mild, the researchers said, with five patients (16.7%) receiving injectable epinephrine.
Further, the treatment group included six patients who also had walnut allergy. Two with recent reactions to walnut were challenged to pecan, uncovering an eliciting dose of 125 mg of protein before the hazelnut OIT began.
After the hazelnut OIT, walnut thresholds included 1,200 mg and 4,200 mg for these two patients. The researchers hypothesized that their walnut reaction thresholds probably increased because the eliciting dose for walnut typically is lower than that for pecan.
The other four patients with walnut allergy did not have any change in their reaction thresholds.
Six patients in the treatment group who also had cashew allergy did not experience any increase in their threshold for cashew. One patient with a negative OFC for cashew before hazelnut OIT began continued to avoid cashew and reacted to a high dose of cashew after the OIT.
Studying the serum of an additional 25 patients with both hazelnut and walnut allergy in the laboratory, the researchers said they could robustly inhibit hazelnut-IgE binding during in vitro testing by pre-blocking with hazelnut, with median maximal inhibition that exceeded 98%.
The walnut IgE binding was minimally inhibited, defined as maximal inhibition of less than 50% per patient, for 11 of these patients (44%), with a maximal walnut inhibition of 14.4%.
Nine patients (36%) had moderate inhibition, defined as maximal inhibition between 50% and 75% per patient, in their walnut-IgE binding, and a median of 57.9% maximal walnut inhibition. Five patients (20%) had high inhibition, defined as more than 75% maximal inhibition per patient, of walnut-IgE binding, with a median maximal inhibition of 88.5%.
Based on these findings, the researchers called hazelnut OIT efficacious and safe, with daily maintenance doses of 1,200 mg of protein enough to achieve and maintain desensitization to 4,000 mg of protein after 6 months.
However, the researchers continued, hazelnut OIT does not achieve cross-desensitization for patients who also have other tree nut allergies except for a few patients with walnut allergy.
“Now we know that patients who are allergic to both hazelnut and walnut or cashew would benefit more from treating the walnut or cashew first. There is a good chance that hazelnut would be cross-desensitized in the process,” Elizur said. “In contrast, treating the hazelnut first would likely not affect the allergy to walnut or cashew.”
These findings can help patients with hazelnut and other tree nut allergies, their families and their physicians decide what kind of OIT they would like to pursue and help them minimize their treatment burden, the researchers said.
“Patients with dual walnut-hazelnut or cashew-hazelnut allergy, should receive walnut or cashew OIT,” Elizur said. “That could minimize the number of treatments they need and the number of allergens they will have to consume long-term.”
Next, the researchers will work “to identify factors that would predict which patients with dual walnut-hazelnut allergy will get cross-desensitized to hazelnut following walnut OIT and which will not,” Elizur said.
For more information:
Arnon Elizur, MD, can be reached at elizura@gmail.com.
Perspective
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I do not think these findings are surprising, but they are important. These findings are helpful because OIT is increasingly being offered for a variety of foods at allergy practices without well-studied commercial products to inform on risks, benefits and long-term outcomes.
Additionally, the approaches (such as dose regimen) and selection of treatment candidates (how allergic they are, age, etc) can be impactful variables for outcomes. Studies using non-pharmaceutically prepared retail purchased foods are emerging and filling this gap in knowledge. That is a reason studies such as this are important.
Also, families often think about “nuts” as a category and ask if “treating” one nut would help allergy to other ones. We know that some nuts are related, such as cashew with pistachio or walnut with pecan, but most nuts are not strongly related. It also appears that some nuts are a more potent version among related ones. For example, while cashew and pistachio are related, cashew appears more potent. The same goes for walnut over pecan. Some studies suggest walnut may have some relation to hazelnut as well. So, there are nuances when you pick a nut for treatment. This study essentially confirmed the expectation that treatment with hazelnut would not significantly impact allergy to cashew or walnut.
The study also adds to the limited literature about the ability to desensitize patients using OIT with hazelnut. It is important to note that this can be successful for most patients, but it also carries risks for allergic reactions, including those treated with epinephrine, as were noted in this study.
There remains a lot to do to acquire data that could inform best practices for OIT. Studies such as this give a snapshot of one protocol applied to a particular, small group of patients. It would be hard for an allergist to give very accurate projections about outcomes or to personalize care until more studies emerge, but the themes do align. This approach carries risks but can achieve desensitization for the majority.
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