Brazil nut
Summary
Bertholletia excelsa, also known as Brazil nut, is an important tree belonging to the family of Lecythidaceae, that has high socio-economic value. It is considered as an indigenous tree to the Amazon tropical rainforest, and its nuts are found to be the only internationally traded seeds that are gathered by forest-based harvesters. The prevalence of Brazil nut allergy has commonly been reported in the United Kingdom (24% and 33%) and United States (12% and 22%). Brazil nut allergy occurs primarily through oral ingestion. Furthermore, allergy to this nut may usually be associated with systemic reactions involving the respiratory tract, cardiovascular, neurological, gastrointestinal system or skin (urticaria or angioedema, and sometimes even life-threatening reactions, like anaphylaxis. Ber e 1 and Ber e 2 are the major allergens identified in Brazil nut, with Ber e 1 being resistant to heat as well as pepsin digestion. It has been reported that Ber e 1-sIgE could serve as a good diagnostic marker in identifying true Brazil nut allergy. Cross-reactivity has been identified with botanically related tree nuts, such as pecan, walnut, hazelnut and cashew, and to some degree with 2S albumins of other plant species, such as cocoa seed, cottonseed, sunflower, sesame seed, rapeseed and castor seed.
Epidemiology
Worldwide distribution
Allergy to Brazil nut is frequently been reported in the United Kingdom (UK), as well as in the United States (US).
A systematic review involving 36 studies conducted among tree-nut-allergic individuals, reported the prevalence of Brazil nut allergy to be between 24% and 33% in the UK and between 12% and 22% in the US.
An increasing trend in the prevalence of Brazil nut allergy was reported in the US. A cross-sectional telephone survey conducted across the US reported the allergy to Brazil nut in 12.5% (8 out of 64) of tree-nut allergic individuals in 1999, which was found to increase to ~28% (25 out of 89) in 2003. However, this 11-year follow-up study in 2010 found the prevalence to reduce to 22.6% (19 out of 84) in tree-nut allergic individuals.
The Pronuts study was a multicenter, European study (London, Geneva, and Valencia) that reported the prevalence of Brazil nut allergy to be 8.2% (10 of 122) among nut-allergic individuals, with the maximum Brazil nut-allergic individuals found in London (10%, 5 out of 50). However, it was not considered to be an index nut, as it was consumed less often across all centers.
Moreover, a study was conducted to examine the cross-sensitization profiles of tree nuts in birch-endemic areas in Finland. The results reported that the prevalence of Brazil nut allergy in tree-nut-allergic subjects, with and without birch sensitization was found to be 18% and 8%, respectively.
Furthermore, in a retrospective study conducted in Taiwan, sensitization to Brazil nut was reported to be 8.3% (28 out of 333) among food-sensitized individuals. Furthermore, it was found to be among the least frequent nut-related sensitization.
Risk factors
Literature data have speculated that allergy to Brazil nut may elicit fatal allergic reactions in sensitized individuals, having a definite atopic family history.
Route Of Exposure
Main
Allergy to Brazil nuts can result in severe reactions, primarily through oral ingestion.
Secondary
Interestingly, a case of sexually-transmitted nut allergy has been reported in a woman who developed immediate allergic reactions (urticaria and angioedema) to Brazil nuts after vaginal intercourse with the partner.
Clinical Relevance
Allergy to Brazil nut may generally be associated with systemic reactions involving the respiratory tract, cardiovascular, neurological, gastrointestinal system or skin (urticaria or angioedema), and sometimes even life-threatening reactions, like anaphylaxis.
Systemic reactions and Anaphylaxis
In a retrospective study conducted among 24 allergic patients (age: 7 months to 56 years) with systemic reactions after skin prick tests to different allergens, three patients were suspected to have allergy to Brazil nut. The systemic reactions were classified into grades based on the clinical symptoms, where grades 1, 2 and 3 were mild reactions, grade 4 was moderate and grade 5 was severe reactions. It was reported that Grade 2 symptoms were observed in two of the patients suspected with Brazil nut allergy. Furthermore, skin reactions, even when exposed to trace amounts (food or minute quantity of inhaled allergen) was observed in one patient, while the other reported of only rhinitis.
Furthermore, in the Pronuts study, an oral food challenge with Brazil nut (n=7) showed the highest symptom severity score (3.1 ± 0.9), when compared to the other nuts (almond, peanut, macadamia, pistachio, walnut, hazelnut, pecan, cashew, pine nut and sesame). The allergic reactions associated with Brazil nut were gastrointestinal (86%), skin, upper and lower respiratory (57% each), and cardiovascular/neurological (14%) reactions.
Interestingly, in a European Anaphylaxis Registry that collected the data on 1970 children, reported a case of a 13-year-old patient who presented with symptoms, such as angioedema, decreased responsiveness, vomiting and dyspnea, within 10 mins of exposure to Brazil nuts.
Allergic rhinitis
The prevalence of allergic rhinitis was reported to be 42.86% in Brazil nut-sensitized patients (n=28), in a retrospective study conducted among 333 food-sensitized individuals in Taiwan.
A study conducted among 56 suspected Brazil nut-allergic patients, allergic rhinitis was reported to be 87.5% (49 out of 56).
Asthma
In a retrospective study conducted among 333 food-sensitized patients (aged 2 to 93 years) in Taiwan, the prevalence of asthma was reported to be 21.43% in Brazil nut-sensitized patients (n=28).
In a study conducted on a cohort of 56 patients with suspected Brazil nut allergy, asthma was found to be prevalent in 71.4% (40 out of 56) of patients.
Atopic Dermatitis
A retrospective study conducted among 333 food-sensitized patients in Taiwan reported the prevalence of asthma to be 46.43% in Brazil nut-sensitized patients (n=28).
In a cohort of 56 patients with suspected allergy to Brazil nut, atopic dermatitis or eczema was reported to be 75% (42 out of 56).
Prevention And Therapy
Prevention strategies
Avoidance
Allergies to tree nuts are commonly being observed, that may become severe in certain individuals, hence it is generally advised to avoid consumption of tree nuts or the food products containing them in these individuals. Furthermore, it has been suggested that food manufacturers should mention allergenic substances on the food label, which include tree nuts as well (including Brazil nuts).
Cross-Reactivity
Several studies have demonstrated that individuals reactive to one tree nut may be sensitized to the other, and this may be due to the cross-reactivity among their pan-allergens or nut storage proteins.
A survey was conducted to determine the true cross-reactivity between different tree-nut antigens. The tree nuts were categorized into two groups of cross-reactive nuts – strong: walnut, pecan, and hazelnut and moderate: Brazil nut, hazelnut, cashew, pistachio, and almond. The immunological cross-reactivity has been reported between Brazil nut, hazelnut, cashew, pistachio, and almond (moderate cross-reactive group), which may be because they belong to the same subclass i.e. Rosidae. However, cross-reactivity has also been observed among the members of the two groups of cross-reactive nuts i.e. between pecan and Brazil nut and between walnut and Brazil nut.
Further, the Pronuts study in Europe found the percentage of co-existent nut allergies with Brazil nut to be 70% with walnut (7 out of 10), 40% each with hazelnut, cashew, macadamia, pecan (4 out of 10), 30% with sesame (3 out of 10), 20% each with pistachio and peanuts (2 out of 10) and 10% with pine nut (1 out of 10) among 10 Brazil-nut allergic patients.
Additionally, IgE-mediated cross-reactivity between Brazil nut and walnut and pecan has also been found. In a study, cross-reactivity patterns were identified by xMAP multiplex food allergen detection assay, that found Brazil nut exhibiting cross-reactivity with cashew, hazelnut, and walnut.
It has been speculated that peanut-allergic individuals may be allergic to Brazil nut too.
Furthermore, moderate degree of co-sensitization exists between Brazil nut and coconut. This was supported by a retrospective analysis study that showed 58% of co-sensitization between Brazil nut and coconut, which was found to be statistically significant (p<0.001).
Structural identity and similarity have been proposed between the 2S albumins of several foods. It has been reported that the 2S albumin of cocoa seed was found to share 44% of identity and 69% of similarity with the 2S albumin of Brazil nut. Furthermore, cross-reactivity as a result of structural homology may be present between the 2S albumin of Brazil nut (Ber e 1) and other plant species, such as cottonseed, sunflower, rapeseed, castor bean, and sesame.
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