Table of Contents

Whole Allergen

f203 Pistachio

f203 Pistachio Scientific Information

Type:

Whole Allergen

Display Name:

Pistachio

Route of Exposure:

Ingestion

Family:

Anacardiaceae

Species:

Pistacia vera

Latin Name:

Pistacia vera

Other Names:

Pistachio nut

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).

Allergen

Nature

Pistachio nut is the seed of Pistacia trees. These trees are considered as one of the oldest flowering nut trees that grow from small to medium and are generally wind-pollinated. They are dioecious (separate male and female trees) (1) and have well-developed resin canals. The leaves are alternate, deciduous or persistent, compound to pinnate, membranaceous or leathery, with elliptical-to-ovate leaflets. The flowers are usually small and unisexual (2). The fruits are flattened, asymmetrical, semidry drupes that consist of a combined exocarp, fleshy mesocarp, and a hard endocarp. The thin off-white endocarp forms the shell, which encloses the seed or nut. It splits open upon ripening, thus revealing the edible embryo. The seed consists of thin skin with light-green flesh with a distinct flavor (1, 3).

Habitat

Pistachio trees are temperate deciduous trees that adjust themselves in dry, hot summers, and moderate winters and can well-tolerate alkaline and saline environmental conditions (1). They grow well in low and high altitudes with a maximum average slope of 25-30% (4).

Taxonomy

Pistachio belongs to the genus Pistacia, and to date, the exact number of species included in this genus is unclear. Pistacia is believed to consist of at least 12 species, namely P. aethiopica, P. atlantica (4 subspecies), P. chinensis (also known as P. phillippinensis, 2 subspecies), P. coccinea (also known as P. weinmannifolia), P. khinjuk, P. lentiscus, P. mexicana, P. saportae (a hybrid of P. lentiscus and P. terebinthus), P. simaruba (also known as Bursera simaruba), P. terebinthus (2 subspecies), P. texana, and P. vera. The P. vera is considered to have the highest economic value because of its edible nuts (1).

Taxonomic tree of Pistachio (5)
Domain	Eukaryota
Kingdom	Plantae
Phylum	Spermatophyta
Subphylum	Angiospermae
Class	Dicotyledonae
Order	Sapindales
Family	Anacardiaceae
Genus	Pistacia
Species	Pistacia vera

Tissue

Pistachio nuts have been found to produce allergic reactions on consumption, and 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 (1).

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 (6). 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) (7). Furthermore, pistachio allergy was found among the top 10 food allergen in Turkish children (8). 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 (9).

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 (10). 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 (11). 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 (12).

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 (1, 10, 13). 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 (3).

Environmental Characteristics

Worldwide distribution

The green pistachio kernels are widely consumed as crude, roasted, salted, or as part of a large variety of food items, including chocolates, cakes, confectionaries, ice-creams, because of its unique taste or aroma. They are even used as folk medicines for some diseases (1, 3). Pistacia vera has been native to Central (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) and West (Afghanistan and Iran) Asia, and then diversified into the Mediterranean region of Europe, North Africa, and the Middle East. It is now cultivated in several countries, which include America (USA and Mexico), Eastern Africa (Madagascar and Mauritius), Northern Africa (Morocco, Tunisia), Western Africa (Cote d’Ivoire), Asia (China, Turkey, Jordan, Azerbaijan), Europe (Greece, Italy, Spain) and Australia (Oceania). As per reports in 2014, the primary global producers for Pistachio nuts were Iran (48.4%), followed by the USA (27.2%), Turkey (9.3%), and China (9.0%). Furthermore, the largest domestic consumption of these nuts was recorded in Turkey, followed by the European Union, China, and the USA (1).

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 (1, 3).

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 (14). 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 (15).

Ando, Watanabe (16) 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 (16). 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 (17).

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 (18).

Asthma

According to a study conducted by Ahn et al., 42.8% of pistachio-allergic patients reported asthma (19).

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 (18).

Asthma was observed in 47.5% of children who were allergic to pistachio and cashew in a study conducted in France (20).

Atopic Dermatitis

In a study conducted by Ahn et al., 57.14% of pistachio allergic individuals reported a history of atopic eczema (19).

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 (18).

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% (20).

Other diseases

Seasonal rhino-conjunctivitis and food-dependent exercise-induced anaphylaxis have been reported due to the ingestion of pistachio in some cases (1).

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 (20).

Diagnostics Sensitization

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 (7, 18, 21).

Molecular Aspects

Allergenic molecules

To date, five allergenic molecules have been identified and characterized and published officially by the World Health Organization and International Union of Immunological Studies (WHO/IUIS) Allergen Nomenclature Sub-Committee for pistachio nut (1, 22, 23).

Among the five pistachio nut allergenic proteins, Pis v 1 and Pis v 2, 3, 5 are the seed storage proteins that belong to the prolamin and cupin protein superfamily, whereas Pis v 4 is a plant defense protein belonging to the manganese superoxide dismutase protein family (1). The table below provides detailed information on each of the allergenic proteins.

Name of allergen	Isoallergen	Biochemical name	Molecular weight (kDa)	Allergenicity
Pis v 1	Pis v 1.01	2S albumin	7	Major allergen. 67.8% of pistachio allergic patients reacted immunologically, accounting for more than 50% IgE-reactivity. 66% homologous to Ana o 3 of cashew
Pis v 2	Pis v 2.01	11S legumin like globulin	32	Major allergen 50% of patients reactive in immunoblots 46-48% sequence homology to Ana o 2 of cashew
Pis v 2	Pis v 2.02	11S legumin like globulin	32
Pis v 3	Pis v 3.01	7S Vicilin	55	Minor allergen 36.8% of patients reactive in immunoblots 80% sequence identity with Ana o 1 of cashew
Pis v 4	Pis v 4.01	Manganese superoxide dismutase	25.7	Major/minor allergen 59% of patients and 40% of patients’ sera were found reactive in immunoblots
Pis v 5	Pis v 5.01	11S legumin like globulin	36	Minor allergen 35.7% of patients reactive in immunoblots

kDa: kilodaltons, IgE: Immunoglobulin E

Biomarkers of severity

There are no allergen components for pistachio available with a quantitative method. However, the cashew Ana o 3 has proven useful when investigating pistachio allergy due to high homology with Pis v 1 compared to whole extract testing with pistachio (24).

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 (25). 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 (7, 20, 26). However, clinically relevant allergy was found to be 34% for pistachio nuts in 29 cashew sensitized children (13). 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 (14). 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 (26). Further, a prospective study conducted in Spain demonstrated no cross-reactivity between mango and pistachio nut (15). 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 (25).

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 (27). Pistachios showed a probability (odds ratio) of 0.64 for a negative skin prick test in peanut-allergic individuals in a study (28), while in another study, weak cross-reactivity between allergens of both was demonstrated (29). 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 (30). Cross sensitization between pink peppercorn, cashew, and pistachio has been demonstrated in 76.2% individuals by skin prick tests (31), while cross-reactivity, partly mediated by 2S albumins, was confirmed in two cases by serum IgE analysis (32). A retrospective analysis study showed 52% co-sensitization between pistachios and coconut but was not significantly associated (33). 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 (34).

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.

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Magnus Borres

Last reviewed: December 2020

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