Pistachio
Summary
Pistachio nut is the seed of the Pistacia trees belonging to the genus Pistacia. The P. vera is the highest, economically cultivated species owing to its edible nuts. It has been native to Central and West Asia and now diversified in Europe, Africa, America, and Australia. The green pistachio kernels are widely consumed as crude, roasted, salted, or as part of the large variety of food items because of their unique taste or aroma. The prevalence of its allergy is rapidly rising and has been across Asia, Europe, and the United States of America. Pistachio nuts have been found to produce allergic reactions like oral allergy syndrome or occasionally anaphylaxis on consumption. Five of its proteins, namely Pis v 1, Pis v 2, Pis v 3, Pis v 4, and Pis v 5, have been identified as having allergenic potential. Pistachio and cashew show a high level of co-sensitization or cross-reactivity since they are genetically closely related nuts. Individuals with cashew nut allergy have a higher risk of co-sensitization with pistachio. Besides cashew, it also shows cross-reactivity with mango seed and other tree nuts (walnut and pink peppercorn).
Epidemiology
Worldwide distribution
The prevalence of pistachio nut allergy is rapidly rising due to an increase in its consumption globally. Several studies have reported its prevalence across Asia, Europe, and the United States of America (USA).
A retrospective study conducted in South Korea reported that pistachio nut allergy prevalence was found to be 0.8% in pediatric patients with a severe allergic reaction to food-induced anaphylaxis. In a study conducted in Israel, clinical allergy to pistachio was observed in 40% of tree nut allergic patients (age range: 3 to 24 years). Furthermore, pistachio allergy was found among the top 10 food allergen in Turkish children. A large prevalence study conducted in the USA for peanut and tree nut allergies found the pistachio allergy in 9.8% of tree nut allergic individuals.
Pistachio nut allergy has become common in Europe. 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 pistachio allergy in tree nut allergic subjects with and without birch sensitization was found to be 55% and 14%, respectively. In a prospective study conducted in Leicester (UK), among South Asian and European children, pistachio nut allergy was reported to be 25.7% in the South Asian and 6.9% in the European population. The Pronuts study, a prospective multicenter European study, found pistachio allergy in 24%, 47.6%, and 13.3% of children in London, Geneva, and Valencia, respectively.
Risk factors
Individuals with cashew nut allergy have reported having a higher risk of co-sensitization with pistachio since they are genetically closely related, showing high homology between allergens of both. Furthermore, in an IDEAL study, co-sensitization between pistachio and cashew nut was reported in 98% of cashew-sensitized individuals. It has been reported that allergic reactions to cashews and almonds were found to be more in individuals living in areas with high cultivation of pistachios.
Route Of Exposure
Main
Oral ingestion of dry pistachio or food containing pistachios can trigger allergic reactions like type I hypersensitivity reactions or oral allergic syndrome with clinical manifestations, such as vomiting, stomach pain, urticaria, pruritus, erythema, eczema, nasal congestion, itchy throat, frequent coughing, wheezing, dyspnea, red/watery eyes, angioedema, swelling of lips, hypotension or even anaphylaxis.
Clinical Relevance
Oral allergy symptoms and Anaphylaxis
In a study conducted on 60 multi-allergic pediatric patients, a double-blind, placebo-controlled food challenge was found to be positive in 100% of pistachio allergic patients. The challenge reported skin reactions, gastrointestinal reactions, and respiratory reactions in 95%, 38%, and 2%, respectively. In a prospective study conducted in Spain on 18 pediatric patients allergic to pistachios and cashew, urticaria and oral symptoms were reported in 38.9% of children, gastrointestinal manifestations in 33.3%, and skin reactions in 16.6% of children. Furthermore, 50% of patients developed moderate anaphylactic reactions, while none developed severe anaphylaxis.
Ando, Watanabe reported a case of a 69-year-old Japanese woman who showed oral allergy syndrome with severe anaphylaxis after consuming pistachio nut. However, pistachio-specific Immunoglobulin E (IgE) antibody reaction was negative in this patient. While another case of pistachio-related anaphylaxis among the 15 proven food-allergic adolescents was observed in a study conducted in Turkey to evaluate the prevalence of IgE-mediated food allergy among adolescents.
Allergic rhinitis
Allergic rhinitis was reported in 20.7% of children with a history of pistachio allergy and in 9.5% of children with a positive oral food challenge (OFC)/anaphylaxis to pistachio in the last 12 months in a prospective cohort study involving 112 children with a history of pistachio and/or cashew nut allergy.
Asthma
According to a study conducted by Ahn et al., 42.8% of pistachio-allergic patients reported asthma.
In a prospective study conducted on 112 children with a history of pistachio and/or cashew allergy, asthma was reported in 46.6% of children with a history of pistachio allergy. Furthermore, 38% of children showed a positive OFC/anaphylaxis to pistachio in the last 12 months.
Asthma was observed in 47.5% of children who were allergic to pistachio and cashew in a study conducted in France.
Atopic Dermatitis
In a study conducted by Ahn et al., 57.14% of pistachio allergic individuals reported a history of atopic eczema.
In a prospective study involving 112 children with a history of pistachio and/or cashew allergy, atopic dermatitis was reported in 22.5% of children with a history of pistachio allergy and 54.5% of children who had a positive OFC or anaphylaxis in the last 12 months due to pistachio.
In a study conducted in France on 51 cashew allergic children, pistachio allergy was reported in 40 patients. In these dual allergic children, atopic dermatitis was observed in 62.5%.
Other diseases
Seasonal rhino-conjunctivitis and food-dependent exercise-induced anaphylaxis have been reported due to the ingestion of pistachio in some cases.
In a study conducted in 51 cashew nut-allergic children in France, 40 children were co-allergic to pistachios and showed rhino-conjunctivitis in 37.5% of children.
Diagnostics
Challenge tests
Oral food challenges (especially double-blind placebo-controlled) are the gold standard for diagnosing clinical reactivity to tree nuts. However, they are time-consuming and associated with the risk of provoking serious reactions.
Cross-Reactivity
Pistachio, cashew, and mango belong to the same botanical family Anacardiaceae. Pistachio and cashew show a high level of co-sensitization or cross-reactivity since they are genetically closely related nuts. Two initial case reports of pistachio allergy have shown to possess specific IgE for cashew nut. The NUTCRACKER study, the IDEAL (Improvement of Diagnostic mEthods for ALlergy assessment) study and a retrospective study conducted in France reported a high prevalence (75-98%) of pistachio sensitization in cashew nut sensitized children. However, clinically relevant allergy was found to be 34% for pistachio nuts in 29 cashew sensitized children. The strong association between cashew and pistachio nut allergy was further confirmed by conducting a double-blind, placebo-controlled food challenge in 42 pistachio allergic patients. All of them were found positive against cashew in the food challenge. The amino acid sequence similarity between cashew and pistachio nut allergens: Ana o 1/Pis v 3 (7S vicilin), Ana o 2/Pis v 2 (11S legumin), and Ana o 3/Pis v 1 (2S albumin) was found to be 78%, 80% and 70% respectively. Further, a prospective study conducted in Spain demonstrated no cross-reactivity between mango and pistachio nut. However, earlier studies have shown that cross-reactivity may exist between pistachio and mango seed and not mango pulp. Hence, patients may still tolerate mango, as only pulp is to be consumed.
Usually, all tree nuts are avoided in peanut-allergic individuals. However, as per a study, pistachios were serologically cross-reactive with peanuts, but 51.6% of peanut-allergic individuals (n=258) were recommended to consume pistachios. Pistachios showed a probability (odds ratio) of 0.64 for a negative skin prick test in peanut-allergic individuals in a study, while in another study, weak cross-reactivity between allergens of both was demonstrated. Furthermore, in a study conducted by Dubiela et al., it was reported that Jug r 6, vicilin protein from walnut might serve as a marker for cross-reactivity between walnut and pistachio and corresponds to Pis v 3, a minor allergen of pistachio. Cross sensitization between pink peppercorn, cashew, and pistachio has been demonstrated in 76.2% individuals by skin prick tests, while cross-reactivity, partly mediated by 2S albumins, was confirmed in two cases by serum IgE analysis. A retrospective analysis study showed 52% co-sensitization between pistachios and coconut but was not significantly associated. Further, cross-reactivity between yellow mustard seeds and pistachio may be possible owing to the sharing of IgG and IgE epitopes with 11S globulins of pistachio.
In all, significant cross-sensitization and cross-reactivity of pistachios have been shown with cashews, pink peppercorn, and walnut; however, a weak association exists with mango, peanuts, or coconut.
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