Tara Haelle

June 23, 2017

HELSINKI — For most children with a tree nut allergy, other nuts and seeds can be introduced into the diet, with challenges and supervision, particularly when they are younger, results from the prospective ProNut study (NCT01744990) shows.

Patients with nut allergies have previously been advised to avoid all nuts, but results from this study suggest that isn't always necessary, and might even lead to more nut allergies. The findings also challenge the belief that peanut and walnut allergies always co-occur, and that cashew and pistachio allergies co-occur.

"All 32 children with pistachio nut allergy had cashew nut allergy, but six cashew-allergic children could tolerate pistachio," said investigator Helen Brough, PhD, a consultant in pediatric allergy at Guy's and St. Thomas' NHS Foundation Hospital and senior lecturer at King's College London.

And "we saw clusters of other nut allergies, most notably between pecan, walnut, and hazelnut," she explained here at the European Academy of Allergy and Clinical Immunology Congress 2017.

The optimal way to prevent and manage nut allergies has been in flux for several years, especially after publication of the LEAP (Learning Early About Peanut) study (N Engl J Med. 2015;372:803-813) and the follow-up LEAP-On study (N Engl J Med. 2016;374:1435-1443). Both showed that the early introduction of peanuts can prevent the development of peanut allergy.

Dr Brough and her colleagues designed their study to determine the actual rate of coexisting peanut, tree nut, and sesame seed allergies. They also wanted to assess the feasibility of multiple nut challenges, precautions related to the introduction of safe nuts, the use of component resolved diagnostics to diagnose tree nut and sesame seed allergy, and quality of life after safe nuts have been introduced into a child's diet.

Although the team has not completed the data analysis, the preliminary findings on improvement in children's quality of life "look promising," Dr Brough told Medscape Medical News.

Multicenter ProNut Study

The multicenter ProNut study involved children 6 months to 16 years of age who had experienced a systematic immunoglobulin E–mediated allergic reaction to a nut in the previous year. All participants had a positive predictive value for allergy to the index seed or nut — almond, Brazil nut, cashew, hazelnut, macadamia, peanut, pecan, pine nut, pistachio, walnut, or sesame seed — above 95%.

Of the 133 study participants, 50 were from London, 42 were from Geneva, and 41 were from Valencia, Spain.

It puts some solid data behind what people are starting to think is the more favorable approach.

The sex distribution was similar in the three groups, but median age was lower in London than in Geneva and Valencia (4.0 vs 5.5 vs 7.0 years). In addition, there were more children younger than 6 years in London than in Geneva and Valencia (60% vs 50% vs 44%).

More children in London than in Valencia had a history of atopic disease (78.0% vs 14.6%) and had atopic disease at baseline (62.0% vs 7.3%).

Over 3 months, the children underwent sequential food challenges to the 11 nuts and seeds, with up to three nuts challenged in a visit. There were 98 positive food challenges among the 50 London children, 94 among the 42 Geneva children, and 64 among the 41 Valencia children.

In the London group, 52% of the children were monoallergic and 48% had coexisting allergies. In Geneva and Valencia, however, only 33% were monoallergic and 67% were allergic to at least two nuts or seeds.

The younger age in the London group likely contributed to the higher monoallergy rate, Dr Brough explained, because the rate of monoallergy was 69% in children 2 years and younger, and none of the other London children 2 years and younger had more than three nut allergies.

The epidemiology of nut allergies was significantly different between Geneva and Valencia, possibly because of differences in age, diet, and environmental exposure to nuts, Dr Brough pointed out.

Table 1. ProNut Study Prevalence of Allergy by Center (n = 133)

Nut or Seed London, % Geneva, % Valencia, %
Peanut 27 18 7
Cashew 12 21 7
Pistachio 10 17 7
Hazelnut 12 13 12
Walnut 13 10 30
Pecan 10 6 25
Sesame 6 4 0
Macadamia 4 4 5
Brazil 4 3 2
Almond 1 2 3
Pine 1 2 2

Of the almost 300 nut allergies that affected the study participants, co-occurrence was significant for many combinations of nuts.

Table 2. Co-occurrence of Nut Allergies (n = 293)

Nut Combination P Value
Pecan and walnut <.0001
Pistachio and cashew <.0001
Macadamia and hazelnut <.0001
Hazelnut, walnut, macadamia, pecan <.0001
Sesame seed and pine nut <.001
Walnut and peanut <.01
Pecan and peanut <.01
Brazil nut and macadamia <.01
Hazelnut and peanut <.05
Brazil nut and peanut <.05
Brazil nut and walnut <.05
Pine nut and macadamia <.05
Almond and macadamia <.05
Sesame seed and hazelnut <.05
Sesame seed and macadamia <.05
Sesame seed and Brazil nut <.05
Almond and pine nut <.05

Although only 2.8% of children allergic to pistachio were not allergic to cashew, the reverse was not true; 16.7% of those allergic to cashew were not allergic to pistachio. Similarly, although 6.1% of those allergic to pecan were not allergic to walnut, 29.5% of those allergic to walnut could safely eat pecans.

Because of the risk for walnut and pecan coallergy in Valencia, challenges to all 11 nuts and seeds were only possible in London and Geneva.

"In Spain, because of the severity of reactions to walnuts in some participants, pecans were not challenged," Dr Brough told Medscape Medical News. The severity of walnut allergy surprised her, she added.

"The thing I took most from the ProNut study is that we need to think about walnut allergy and how severe walnut allergy can be," she explained. "It's not something that I was anticipating, because often you get lower allergy testing to walnut, but actually they can have very severe allergic reactions. That was one of my on-the-shop-floor experiences, and for pecan also."

Walnut is the most common nut allergy in the United States, said Hugh Sampson, MD, professor of pediatrics at Mount Sinai Hospital in New York City, who presented an abstract on peanut allergy during the same session.

"The one thing that's important is this differential between cashew and pistachio allergy, and also the walnut and pecan allergy," he told Medscape Medical News. "Up until today, if I had somebody who reacted to walnut, I probably wouldn't bother challenging pecan, but now, clearly, there is a subset that is okay doing that."

Overall, these new data are valuable to those in clinical practice trying to make sense of the changing evidence related to nut allergy, he explained.

"It puts some solid data behind what people are starting to think is the more favorable approach," Dr Sampson explained. "Hopefully, there will be more introduction of nuts, and I think one of the points Dr Brough made is that this is something we have to look at early."

As the LEAP trial did, these new data give "us more impetus to put some of these tree nuts into the diet early to try to prevent the development of nut allergy," Dr Sampson said.

Dr Brough reports receiving research support from ThermoFisher Scientific, Stallergenes, and Meridian Foods; consulting for Mead Johnson Nutrition; and serving on the speaker's bureau or receiving honoraria from Allergy Therapeutics, Nutricia Advanced Medical Nutrition, and Nutricia Early Life Nutrition. Dr Sampson reports consulting for Allertein Therapeutics in the development of a therapy for peanut allergy, and is employed by DBV Technologies.

European Academy of Allergy and Clinical Immunology (EAACI) Congress 2017: Abstract 0124. Presented July 20, 2017.

Follow Medscape Allergy & Clinical Immunology on Twitter @MedscapeAllergy and Tara Haelle @TaraHaelle

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