Cashew nut

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Code: f202
Latin name: Anacardium occidentale
Source material: Shelled nuts
Family: Anacardiaceae

Allergen Exposure

Geographical distribution

The Cashew nut comes from the Cashew nut tree, a member of the Anacardiaceae family, which includes a number of dermatitis-inducing plants such as poison ivy, poison oak, poison sumac and lacquer sumac. The tree is native to Brazil but is grown in other parts of the world, and the nut is now also exported from southern India, Mozambique, Tanzania and Kenya. This is a small perennial evergreen tree growing to 12 m tall, with a short, often irregularly-shaped trunk. The leaves are simple, alternate, spirally arranged, leathery, elliptic or obovate, up to 22 cm long and 15 cm broad, with a smooth margin.

The buds grow on terminal panicles which are up to 26 cm long. The flowers change from pale green to reddish as they develop and have 5 slender, pointed petals 7-15 mm long. The Cashew tree flowers once a year and pollination is mainly by insects. In the northeast region of Brazil, where the tree grows in great numbers, it flowers once a year between August and October.

The pear-shaped accessory fruit or false fruit is called the Cashew apple. This measures 4-8 cm by 10-20 cm and is yellow or red, soft and juicy, and rich in vitamin C. But the 3 cm, edible, smooth-kernelled, kidney-shaped nut (botanically defined, a seed) that grows at the end of the Cashew apple is the real fruit.

The Cashew nutshell has 3 layers. The outer leathery exocarp and the thin, hard, inner endocarp enclose a honeycombed mesocarp which is filled with an oily fluid containing substances that are themselves allergens: cardol, cardanol, 2-methylcardol and anacardic acid. This oily brown Cashew nut shell oil causes an immediate vesicant reaction because of its high concentration of phenols. Cashew wood exudes a yellow gum that also can cause vesicant reactions. It is used in the production of varnish, insect repellents, and adhesives. The tree bark produces thick resinous latex that turns black on contact with air and may result in blistering reactions on contact (1-3).

The oily substance in the shells must be removed before the nut is processed for consumption. Unaided shelling of the nuts can easily produce painful dermatitis (similar to poison-ivy rashes). The nuts are therefore usually first put through a hot bath for easy removal of the shells. The heating process causes the pericarp to burst, releasing the Cashew nutshell liquid (CNSL) and at the same time decarboxylating the anacardic acids into less allergenic cardanols. The nuts are then centrifuged in sawdust to remove the endocarp and residual phenols. Heating, water washing and agitation constitute an alternative process (4). Next, the endocarp is removed to yield an edible nut. Raw Cashews are not processed to the same extent and may be contaminated with the shell oil (1).

The resorcinol cardol is both an irritant and an allergen, with side chains similar to the side chains of poison ivy and poison oak. Early oral exposure to resorcinols such as cardol appears to protect against contact dermatitis to catechols (present in poison ivy), whereas early cutaneous exposure to catechols predisposes to an allergic reaction to resorcinols. The concentration of phenols in the Cashew nutshell and bark is so high that contact with them causes immediate vesicant reactions. Africans have used CNSL and Cashew bark in ritual scarification and keloid formation, and it has been used for wart removal (1).

Therefore, Cashew nuts generate both allergy to Cashew nut shell oil and allergy to the nut itself. As far as the shell is concerned, roasting diffuses irritating vapours, but unless roasting is complete, not all the allergens are inactivated. Problems also arise when children play with the raw shells or when improperly shelled Cashew nuts are sold (5).

Environment

Cashew nuts are edible and popular snacks. They are also used as an ingredient in many processed foods such as nut "butters", bakery and confectionery products, and pesto. They are a common component of oriental foods.

The Cashew apple is used for its juicy but acidic pulp, which can be eaten raw or used in the production of jam, chutney, or various beverages. Its juice can also be processed and distilled into liquor or consumed diluted and sugared as a drink.

Unexpected exposure

See under Environment.

Allergens

Cashew food allergy is associated with the presence of IgE antibodies directed against the major seed storage proteins in Cashew, including the 13S globulin proteins (legumin group) and 2S albumins, both of which represent major allergen classes in several plant seeds. The 13S globulin proteins are in the 31-35 kDa range, whereas the 2S albumins are low-molecular-weight polypeptides (6). In 3 individuals who experienced anaphylaxis to Cashew nut, a number of other allergens of 15, 30 and 60 kDa were shown to be involved, the 15 kDa one possibly being a 2S albumin (7).

The following allergens have been characterised to date:

  • Ana o 1, a 7S vicilin-like globulin, a major allergen. (6,8-11).
     
  • Ana o 2, an 11S globulin, a 33 kDa, legumin-like protein, and a major allergen (9,11-12).
     
  • Ana o 3, a 2S albumin, a 12.6 kDa protein and a major allergen (6, 9,11,13-14).
     
  • Ana o Profilin (15).

Two isoforms of Ana o 1, Ana o 1.0101 and Ana o 1.0102, have been characterised. Ana o 1 and Ana o 3 have been expressed as recombinant allergens.

Ana o 1, a vicilin-like protein, has been shown not to share linear epitopes with Peanut vicilin. Recombinant Ana o 1 bound with 50% of sera from 20 patients with Cashew nut allergy, and with sera of 25% of 8 Cashew-tolerant patients with allergies to other tree nuts (8).

Ana o 2, a legumin-like protein, shows on immunoblots as a major band at approximately 33 kDa and a minor band at approximately 53 kDa. Legumins represent the main storage proteins in Cashew, accounting for approximately 50% of the total seed protein. Thirteen of 21 sera (62%) from Cashew-allergic patients were reactive to Ana o 2 (12).

Ana o 3 was shown to bind with sera of 21 (81%) of 26 Cashew-allergic patients (13).

A profilin has been detected in Cashew nut, at levels which may result in no clinical adverse effects (15). Its clinical relevance was not evaluated.

Potential cross-reactivity

Significant cross-reactivity has been reported between Pistachio nut and Cashew nut (13,16-17).

Cross-reactivity between Cashew nut and Walnut is possible, as a result of Ana o 2, the legumin protein which is a major allergen in Cashew nut and present in Walnut (13); and the cross-reactivity is also suggested by in vitro studies. A recent study described significant sequence homology between the recombinant Jug r 4 from Walnut, and Hazel nut and Cashew legumin allergens (18).

An early study reported little cross-reactivity between Cashew and Peanut or Brazil nut. (19) Although Cashew nut and Peanut vicilins share 27% identity, they were reported to not share linear epitopes, and hence did not appear to be cross-reactive (8,12,20). However, a recent study argued that the vicilin allergens of Peanut (Ara h 1), Walnut (Jug r 2), Hazel nut (Cor a 11) and Cashew nut (Ana o 1) share structurally related IgE-binding epitopes; that this epitopic community creates a risk of cross-sensitisation; and that a restriction or avoidance of tree nuts should be recommended to Peanut-sensitised individuals (10).

A 19 kDa protein from Buckwheat was reported to have weak homology to the vicilin-like allergens of Cashew, Walnut (Jug r 2), and 7S globulin from Sesamum indicum (21).

Conformational analysis of the legumin allergens of Peanut (Ara h 3), Walnut (Jug r 4), and Hazel nut (Cor a 9), along with Ana o 2 of Cashew nut, showed that consensual surface-exposed IgE-binding epitopes exhibited some structural homology. The authors suggested that individuals allergic to Peanut should avoid the other 3 nuts to prevent possible allergic reactions (14).

Pectin has been shown to contain all of the allergen epitopes of Cashew nut, whereas Cashew nut does not exhibit all of the epitopes of pectin. The clinical significance of this fact has not yet been established, and further studies are required to characterise these cross-reacting allergens (22). However, a recent study reported that Cashew nut allergy, and possibly Pistachio nut allergy, may be associated with pectin allergy, and the possibility of pectin allergy should be considered in Cashew- or Pistachio-allergic patients who have unexplained allergic reactions. The study described a 3 1/2-year-old boy who developed anaphylaxis after eating Cashew nut and later after eating a pectin-containing fruit "smoothie". The child had skin reactivity to pectin and a high level of IgE antibodies to Cashew nut and Pistachio nut, as well as a low level of IgE to Grapefruit, to which he had previously also reacted. The pectin in the smoothie was confirmed to be of citrus origin (23).

Cardol, found in the Cashew nut shell, is not usually present in the nut unless contamination occurs. An early study reported cross-reactivity of poison ivy and Cashew nut as a result of the nut being contaminated with cardol (24).

Clinical Experience

IgE-mediated reactions

Cashew nut may commonly induce symptoms of food allergy, atopic dermatitis and other hypersensitivity reactions in sensitised individuals (7,25-29). Tree nuts and Peanuts are among the most common foods responsible for causing IgE-mediated food hypersensitivity. Tree nut and Peanut allergy is usually lifelong. Cashew nut allergy may present as a singular event or in conjunction with allergy to other tree nuts.

Although typically very severe, Cashew nut allergy was initially thought to be very rare; 1 out of 1,218 in a paediatric population on the Isle of Wight, UK, was found to be Cashew nut-allergic. (26) However, Cashew nut, initially regarded as a novel food but now increasing in popularity as a snack, is regarded as an “emerging” allergen, (30) and hypersensitivity reactions are expected to increase (27). In particular, with the increasing consumption of Asian cuisine, containing foodstuffs such as Sesame, Brazil nuts and Cashew nuts, the associated allergies are more frequent than they were formerly (31).

Cashew nut allergy is now the second most commonly reported tree nut allergy in the United States (13). Besides the protein allergens, Cashew nuts contain oleoresins which can cause contact dermatitis and are thought to cause gastrointestinal, systemic and allergic manifestations. In a French study that evaluated, using DBPCFC, 163 asthmatic and food-allergic children for food-induced asthma, Cashew nut was the ninth most frequent offending food and affected 2.1% of the group (32). The prevalence of Cashew nut hypersensitivity has also been reported to be increasing in China, as attested in a study of 30 patients with Cashew nut allergy (33). A retrospective review of 213 Australian children with Peanut or tree nut allergy reported that anaphylaxis to Cashew nut was more common than to Peanut (74.1% vs. 30.5%) (34).

Cashew nut allergy may span a wide age range, and age of onset may vary widely. In a study of 21 Cashew nut-allergic subjects ranging from 25 to 62 years of age, age of onset varied between 1 year and 15 years, with 15 subjects experiencing onset at less than 3 years of age (12).

In a study of 42 children with Cashew nut allergy, the mean age at the first reaction was 2 years, and the mean age at diagnosis was 2.7 years. One in 5 children (12%) had a prior history of exposure to Cashew nuts. Fifty-six per cent had skin symptoms, 25% had respiratory symptoms, and 17% had gastrointestinal symptoms. Eighteen children had proven associated food allergies (Pistachio [7], Hen's egg [5], Mustard [3], Shrimp [2], Cow's milk [1]). Eight children had positive food challenges. The study concluded that the increase in Cashew allergy is worrying because it affects young children who may have a reaction without ever having been exposed to Cashews. The authors also point out that a clinical history may be sufficiently suggestive to allow diagnosis of Cashew allergy without recourse to food challenges (35).

Significantly, minimal contact may be required to precipitate symptoms. In a study of Cashew-allergic individuals, 48% reacted to minimal contact with Cashew, i.e., smelling, touching, or tasting, but not eating Cashew. The authors point out that reactions could be as severe as those from Peanut allergy (36).

Oral allergy has been described in a 26-year-old woman, who experienced tingling on her tongue and itching both in the throat and on the face immediately after she put a Cashew nut onto her tongue. SPT and serum IgE antibody tests were positive for Cashew nuts and negative for Peanuts and other tree nuts. Skin reactivity for Cashew nuts normalised one year after she began avoiding Cashew nuts (37).

Life-threatening anaphylactic reactions to Cashew nut have been reported, and one study reported on 15 subjects (6). Anaphylaxis to Cashew nut was reported in a 20-month-old girl who developed facial angioedema and generalised urticaria immediately after eating a Cashew nut; in a 12-year-old girl who experienced oral itching, generalised urticaria, wheezing, dyspnoea, and dizziness 15 minutes after eating a single Cashew nut; and in a 36-year-old woman who developed generalised erythema, rhinorrhoea, dyspnoea, dysphagia, nausea, vomiting and diarrhoea immediately after eating ice cream containing Cashew nut. SPT and IgE antibodies to Cashew and Pistachio nuts were positive in all 3 patients (7). A 42-year-old patient allergic to Pistachio who had anaphylaxis to Cashew nuts was described. Symptoms included mouth and lip itching, slurred voice, dyspnoea and vomiting a few minutes after eating some Cashew nuts. History disclosed 3 previous episodes of adverse reactions to Pistachio. Allergen-specific IgE was negative for both (38).

A 2007 report from Holland points out that in recent years there has been an increasing number of patients with an anaphylactic reaction after eating small amounts of Cashew nut. The report describes a boy aged 7 and 2 girls aged 9 and 10 years, with heterogeneous case histories involving allergic upper airway and conjunctival symptoms and constitutional eczema, who presented with anaphylactic symptoms after ingestion of nuts. Allergy to Cashew nut was diagnosed in the first 2 and for Peanut in the third (29).

Cashew nut is reported to cause more severe reactions than Peanut. In a study to confirm this, children whose worst-ever reaction was to Cashew nut were matched with 2 children each whose worst-ever reaction was to Peanut, resulting in a total of 47 children in the Cashew group being matched to 94 in the Peanut group. There were no differences in overall clinical features between groups, except for asthma, which was more prevalent in the Peanut group. Wheezing and cardiovascular symptoms were reported more frequently during reactions in the Cashew group, compared with the Peanut group. Furthermore, the Cashew group had received intramuscular adrenaline more frequently. The authors concluded, by using case-matching, that severe clinical reactions occur more frequently in Cashew than in Peanut allergy (39).

Inhalation of pectin has been identified as a cause of occupational asthma. The following study describes the first known case of allergy to ingested pectin. A 3 1/2-year-old boy developed anaphylaxis once after eating Cashew nut and later after eating a pectin-containing fruit “smoothie”. Significant levels of IgE antibodies for Cashew and Pistachio were demonstrated, along with skin reactivity for pectin. The pectin in the smoothie was confirmed to be of citrus origin, and the authors report cross-reactivity between pectin and Cashew (23).

Anaphylactic reactions may not always be obviously attributable to Cashew nut, in particular when the nut is hidden in a compound food. For example, fatal anaphylactic reactions reported in 2 adolescents had very different but in both cases cryptic causes: a sandwich containing Cashew nut, and candy. (40) A report was made of an allergic reaction to Cashew that resulted in upper airway obstruction and was initially misdiagnosed as foreign body aspiration. (41) Cases of “idiopathic” anaphylaxis may in fact result from inadvertent contact with Cashew nut (42).

An anaphylactic reaction to Cashew nut was reported in a non-atopic 60-year-old man 25 days after he received a liver allograft from a 15-year-old atopic boy who died of anaphylaxis after Peanut ingestion. The liver recipient had no history of nut allergy. Post-transplantation skin prick test results were positive for Peanut, Cashew nut, and Sesame seed, and the donor had allergen-specific IgE antibodies to the same 3 allergens. The authors stated that this case illustrated that transfer of IgE-mediated hypersensitivity can occur after liver transplantation, with potentially serious consequences (43).

Atopic dermatitis and allergic contact dermatitis (3-4,44-48) from ingestion of or contact with Cashew nut have frequently been reported, as well as from contact with the nut shell (49).

Hypersensitivity may result from contact with the urushiol present in the shell and contaminating the nut, or from the Cashew nut protein. Allergic contact dermatitis to Cashew nut may simulate photosensitivity eczema (50). Furthermore, Cashew nut dermatitis should be a consideration for individuals travelling to countries where Cashew nut is a frequent ingredient in food (51).

In an American study of 165 patients aged 4 months to 22 years with atopic dermatitis, 7 foods (Cow's milk, Hen's egg, Peanut, Soy, Wheat, Cod/Catfish, Cashew) accounted for 89% of the positive challenges (25).

Other reactions

Pollen from the Cashew nut tree may result in sensitisation, asthma and allergic rhinitis. In a study of 80 Brazilian subjects with allergic asthma, as documented by previous positive skin test reactions to various pollens, all 80 were shown to have significant skin reactivity to pollen from this tree. The authors suggested a correlation between the Cashew tree flowering period and an increased number of allergic asthma cases (52). Similarly, in an Indian study of 65 subjects with allergic asthma, 26 (40%) had positive SPT to pollen of this tree. Bronchial provocation tests were performed in 22 of the 26 patients, and 20 (90.9%) had a positive result. Allergen-specific IgE for Cashew tree pollen was raised (53).

The urushiol dermatitis caused by plants of the Anacardiaceae family is the most common cause of acute allergic contact dermatitis and systemic dermatitis. Urushiol, containing cardol and ancardic acid, is found in Cashew nut shell oil. A study of 54 individuals who developed a poison ivy-like dermatitis 1 to 8 days after eating imported Cashew nuts (contaminated by urushiol from the Cashew shell oil) described how the patients had a very pruritic, erythematous, maculopapular eruption that was accentuated in the flexural areas of the body. Three had blistering of the mouth, and 4 had rectal itching. Nine who reacted to the Cashew extract also reacted to poison ivy urushiol (54).

Systemic contact dermatitis to raw Cashew nut found in imported pesto sauce has been described. In this instance, the cause was attributed to the nut shell oil's cardol and anacardic acid. The clinical expressions were dermatitis with flexural accentuation, typically distributed on the extremities, groin, and buttocks, and occurring generally 1 to 3 days after ingestion of raw Cashew nuts contaminated with allergenic oil (3).

Urushiol dermatitis has been described following the ingestion of homemade Cashew nut butter contaminated by Cashew nut shell oil, which resulted also in perianal contact dermatitis. The severe systemic dermatitis required 3 weeks of systemic steroid therapy. The authors state that perianal eruptions may be due to materials deliberately applied to the anogenital region or to ingested antigens that remain sufficiently intact within the faeces to affect perianal skin (55).

In a series of patients with Cashew nut dermatitis, patch tests were positive to moistened, crushed raw Cashews but not to roasted Cashews in patients with an internal-external contact type of hypersensitivity to raw Cashews purchased from organic food stores. Control patients without a history of poison ivy sensitivity did not react to the raw Cashew patch test and did not develop the rash on ingestion of large amounts of raw Cashews. Affected patients had eaten between 150 and 450 g of Cashews, prompting the authors to conclude that large quantities of allergen in raw Cashews would provoke the syndrome in highly sensitive people (3). (Other studies have demonstrated that very low levels of allergen are required as a trigger, suggesting that these cases involve a protein allergen, whereas in the cases in which high levels are required for a reaction, the reaction is to a substance such as cardol (4)).

With the precautions taken today to avoid contamination of food products with Cashew urushiols, it is rare to find a case of Cashew nut dermatitis as a result of urushiol in the United States (55).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.