Review
Prevalence and natural history of tree nut allergy

https://doi.org/10.1016/j.anai.2020.01.024Get rights and content

Abstract

Objective

Tree nuts are common causes of food-related allergic reactions and anaphylaxis. Resolution of tree nut allergy is thought to be low, yet studies of the natural history of tree nut allergy are limited. This review summarizes the available literature regarding tree nut allergy prevalence and natural history and discusses emerging diagnostic and prognostic developments that will inform clinical management of tree nut allergy.

Data Sources

A comprehensive literature search using PubMed was performed.

Study Selections

Peer-reviewed publications relating to tree nut allergy prevalence, resolution, and diagnosis were selected, and findings were summarized using a narrative approach.

Results

Tree nut allergy prevalence varies by age, region, and food allergy definition, and ranges from less than 1% to approximately 3% worldwide. Reports on the natural history of tree nut allergy data are limited to retrospective clinical data or cross-sectional survey data of self-reported food allergy, with reported resolution ranging from 9% to 14%. Component-resolved diagnostics and basophil activation testing offer the potential to improve the diagnostic accuracy and predicted prognosis of specific tree nut allergy, but studies are limited.

Conclusion

Tree nut allergy remains an understudied area of food allergy research with limited region-specific studies based on robust food allergy measures in population cohorts with longitudinal follow-up. This currently limits our understanding of tree nut allergy prognosis.

Introduction

Nut is a culinary term used to describe any large, oily kernels found within a shell and used in food.1 The culinary nuts most likely to result in immunoglobulin E (IgE)-mediated allergic reactions are peanut and what is collectively referred to as tree nuts. Tree nut definitions vary worldwide, but the common tree nuts include almond, Brazil nut, cashew, hazelnut, pecan, pistachio, and walnut. Tree nut allergies have emerged as 1 of the biggest clinical challenges and research priorities in food allergy. Together with peanut, tree nuts are the most common trigger of adverse food reactions and fatalities, with prevalence reported to be increasing and considered to be lifelong.2, 3, 4 Unlike peanut allergy, however, tree nut allergy remains understudied, and primary and secondary prevention strategies are unknown. This review outlines the current evidence to date surrounding the prevalence and natural history of tree nut allergy, and outlines the emerging diagnostic and prognostic developments that will further inform clinical management of tree nut allergy.

Section snippets

Prevalence

Tree nut allergy prevalence varies by region, age, and the definition used for diagnosis. A systematic review of global tree nut allergy prevalence found estimates mostly based on self-reported data ranging from 0.05% to 4.9%.1, 3 Significant limitations were present in most studies, risking overestimation of prevalence, because of diagnosis based on self-reported food allergy or the inclusion of oral allergy syndrome/pollen food allergy syndrome (OAS/PFS) in tree nut allergy definitions.

Co-allergies Patterns among Nuts

High sequence identity is found between tree nuts and even between tree nut and some legumes (peanut) and seeds, resulting in high rates of reported co-sensitization. However, distinguishing sensitization from clinical allergy relies on labor-intensive oral food challenges (OFC), often to several tree nuts. For this reason, much of the tree nut co-allergy data available to date are limited to sensitization data and retrospective allergy clinic data where significant biases can occur.

Peanut and Tree Nut Co-allergy

In vitro cross-reactivity between peanuts and tree nuts has been reported as high as 86%,18 and tree nut sensitization among those with peanut allergy as high as 87%.18, 20, 21, 22 However, the coexistence of clinical peanut and tree nut allergy is lower, with estimates based on self-report between 20% and 60%.23, 24, 25, 26 Studies based on OFC-confirmed outcomes report much lower rates of tree nut allergy among those with peanut allergy. A retrospective review from the United Kingdom showed

Tree Nut Co-allergy

Studies of co-allergy among the individual tree nuts are limited, but the same observation of higher levels of co-sensitization and lower rates of clinical allergy reported for peanut and tree nut are reported, highlighting the limitation of relying on sensitization data alone.30

A single-center retrospective US study of 159 tree nut challenges performed in tree nut–sensitized individuals found a co-allergy rate of 24% to 1 or more tree nuts.28 To date, population-based studies with

Development of Tree Nut Allergy

Development of tree nut allergy in childhood is also understudied. Based on US registry data published in 2001, the median age of initial peanut reaction has been reported as 14 months of age and 36 months for tree nuts.19 However, with the change in infant feeding recommendations to introduce peanut and other common allergens before 12 months of age, initial reactions to tree nut may now be occurring at an earlier age. Early tree nut sensitization has been reported among those with peanut

Tree Nut Allergy Diagnosis

Tree nut allergy is diagnosed in the same manner as other food allergies, with a combination of a thorough clinical history, serum-specific IgE, skin prick testing (SPT), and OFC. Without a clear history of a clinical suspicion for allergy, tree nut serum-specific IgE and SPT alone only serve as indicators of sensitization. Increasing magnitude of SPT and sIgE is associated with an increased risk of food allergy, and thresholds for these tests, which have 95% positive predictive value (PPV) to

Resolution of Tree Nut Allergy and Predictors of Persistence

As with other aspects of tree nut allergy, the natural history of tree nut allergy is another understudied area. This is largely because of the absence of prospective studies that have captured cases of tree nut allergy at the population level. Initially peanut and tree nut allergy were thought to be lifelong conditions. The first study to find evidence that some children may outgrow tree nut allergy was reported in 2005 (Table 2). Fleischer et al4 reviewed clinic records to identify 278

Conclusion

Determining the most clinically relevant tree nuts is complex, with multiple culinary nuts defined as a tree nuts and individual allergy prevalence varying regionally. Current diagnostic methods poorly differentiate between sensitized and clinically allergic individuals, with diagnosis heavily reliant on costly and time-consuming oral food challenges. This is further complicated for tree nut allergy because of high prevalence of co-sensitizations, necessitating the need for several individual

References (62)

  • S.L. Taylor et al.

    Establishment of reference doses for residues of allergenic foods: report of the VITAL Expert Panel

    Food Chem Toxicol

    (2014)
  • T.D. Dang et al.

    Increasing the accuracy of peanut allergy diagnosis by using Ara h 2

    J Allergy Clin Immunol

    (2012)
  • R.J.B. Klemans et al.

    The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model

    J Allergy Clin Immunol

    (2013)
  • L.J.N.M.D. Masthoff et al.

    Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults

    J Allergy Clin Immunol

    (2013)
  • S.M.D. Savvatianos et al.

    Sensitization to cashew nut 2S albumin, Ana o 3, is highly predictive of cashew and pistachio allergy in Greek children

    J Allergy Clin Immunol

    (2015)
  • K.M. Saarinen et al.

    Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status

    J Allergy Clin Immunol

    (2005)
  • L.P. Shek et al.

    Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy

    J Allergy Clin Immunol

    (2004)
  • T. Boyano-Martinez et al.

    Prediction of tolerance on the basis of quantification of egg white-specific IgE antibodies in children with egg allergy

    J Allergy Clin Immunol

    (2002)
  • T. Weinberger et al.

    Current perspectives on tree nut allergy: a review

    J Asthma Allergy

    (2018)
  • R.S. Gupta et al.

    The prevalence, severity, and distribution of childhood food allergy in the United States

    Pediatrics

    (2011)
  • V. McWilliam et al.

    The prevalence of tree nut allergy: a systematic review

    Curr Allergy Asthma Rep

    (2015)
  • V. McWilliam et al.

    Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort

    J Allergy Clin Immunol

    (2018)
  • M. Sasaki et al.

    Prevalence of clinic-defined food allergy in early adolescence: the SchoolNuts study

    J Allergy Clin Immunol

    (2017)
  • L.P. Shek et al.

    A population-based questionnaire survey on the prevalence of peanut, tree nut, and shellfish allergy in 2 Asian populations

    J Allergy Clin Immunol

    (2010)
  • T.F. Leung et al.

    Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors

    Pediatr Allergy Immunol

    (2009)
  • K. Ahn et al.

    Prevalence of immediate-type food allergy in Korean schoolchildren: a population-based study

    Allergy Asthma Proc

    (2012)
  • Y. Wang et al.

    Increasing hospital presentations for anaphylaxis in the pediatric population in Hong Kong

    J Allergy Clin Immunol Pract

    (2018)
  • M. Panjari et al.

    Nut allergy prevalence and differences between Asian-born children and Australian-born children of Asian descent: a state-wide survey of children at primary school entry in Victoria, Australia

    Clin Exp Allergy

    (2016)
  • J.J. Koplin et al.

    Increased risk of peanut allergy in infants of Asian-born parents compared to those of Australian-born parents

    Allergy

    (2014)
  • C. Venter et al.

    Prevalence of sensitization reported and objectively assessed food hypersensitivity amongst six-year-old children: a population-based study

    Pediatr Allergy Immunol

    (2006)
  • C. Venter et al.

    Prevalence and cumulative incidence of food hypersensitivity in the first 3 years of life

    Allergy

    (2008)

    • Cited by (0)

    Disclosures: VMC reports personal fees from speaker honorariums for Aspen Global, Abbott Australasia, and Nestle Health Sciences and personal fees from Advisory Panel Consultancy for Nestle and Nutricia outside the submitted work. The rest of the authors declare no conflicts of interest.

    Funding Sources: None.

    View full text
    © 2020 Published by Elsevier Inc. on behalf of American College of Allergy, Asthma & Immunology.