Route Of Exposure

Allergen Exposure

Pine nuts, coming from several varieties of Pine trees, are abundant in south-western North America, but also in similar climates elsewhere, most notably the Mediterranean. They were an important food source for Native Americans. The high-fat, high-protein, ivory-coloured nuts are actually inside the Pine cone, which generally must be heated to facilitate their removal. The nuts, though tiny (about 1.5 cm in length), must be taken out of their thin, soft shells as well. This long process is what makes the nuts so expensive.The Pine nut has in many varieties, including the Italian or Mediterranean and the Chinese.

Pine nuts are often sold as a health product. They are used raw and intact, ground up, and for oil. They are popular as a snack, in salads, and in sweet and savoury ethnic dishes, especially the classic Italian pesto and as a seasoning in the cuisine of the Mediterranean area of Spain.

Clinical Relevance

Allergens

No allergens from this plant have yet been characterised.

In previous studies, 30 protein bands have been demonstrated in Pine nut, 3 of which (66 to 68 kDa in size) bound IgE in a Pine nut-allergic patient's serum in immunoblot studies. A 17 kDa protein has also been detected and found to be sensitive to reducing agents, losing its IgE-binding properties through reduction. A 17 kDa protein was isolated by serum from 2 young children who experienced anaphylaxis to this nut. Pine nut protein bands of 30 and 44 kDa, which disappear in the inhibition of immunoblotting with Peanut, have been isolated. An important allergenic band of 50 kDa, which disappeared after blotting inhibition with an Almond extract, has also been reported.

Potential Cross Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected. Cross-reactivity between the botanically related seeds of Pinus pinea and P. cembra has been demonstrated by RAST inhibition. It was postulated, based on the cross-reactivity between Pine nut and Pine pollen extracts, that co-sensitisation to these allergens could be the reason for a case of Pine nut allergy described in a single patient with Pine pollen allergy. However, the allergens were not studied in this case, and among individuals who had experienced anaphylactic reactions to Pine nut, none were Pine tree pollen-allergic.

Studies have also reported the existence of common antigenic proteins between Pine nut and Peanuts, and cross-reactivity between Pine nut and Almond; however, many individuals with allergy to Pine nut have no IgE antibodies to these nuts and do not experience allergic reactions following ingestion.

Clinical Experience

Pine nut may commonly induce symptoms of food allergy in sensitised individuals.

A study reports on 4 paediatric patients with allergy reactions on ingestion of Pine nuts. Ages ranged from 12 months to 6 years. All patients had a history of atopy. Severe systemic reactions occurred in 3 cases. Two of the children had allergic reactions to other nuts. In all cases, both the skin test and the serum IgE antibody test were positive.

Reactions may be severe. Anaphylaxis after Pine nut ingestion has been often reported. Anaphylaxis after eating Pine nut was reported in a 10-year-old boy, who had been previously diagnosed with seasonal rhinoconjunctivitis with sensitisation to grass and Olive pollen. A 21-year-old white male developed life-threatening systemic anaphylaxis within seconds of ingesting a small amount of a cookie containing Pine nut. SPT, ELISA, and basophil histamine release studies demonstrated Pine nut-specific IgE antibodies. A patient with Bird-Egg Syndrome who experienced an anaphylactic reaction after eating some of her Parrot's food (containing Pine nut) has been reported. Allergen-specific IgE against Pinus pinea (Stone pine) was demonstrated by IgE antibody testing.

Two young girls who experienced anaphylaxis caused by small amounts of Pine nuts were described. Allergy to Pine nut was confirmed by skin reactivity and IgE antibodies, but negative tests for other nuts and for Pine pollen. The patients had IgE antibodies directed against a Pine nut protein band of approximately 17 kDa that could be considered the main allergen. The 17 kDa protein could be correlated with the severe clinical symptoms. Both girls were monosensitised to Pine nut.

A 22-year-old man, without a history of atopy or drug allergy, presented with difficulty in breathing and swallowing, profuse sweating, abdominal pain, and visual disturbances 15 minutes after eating several Pine nuts.

Acute anaphylaxis after skin testing for Pine nut was reported in a 20-year-old woman. Her initial complaints were that she had developed generalised urticaria, swelling of the face and dyspnoea after eating a salad containing Pine nuts. Similar symptoms were experienced after the skin test, including a strong local skin reaction.

Anaphylaxis to Pine nuts was described in a 53-year-old man, who experienced angioedema, acute dyspnoea and circulatory collapse for the first time after a meal of spaghetti and pesto sauce (olive oil, herbs, Pine nuts and sardines). Skin reactivity was demonstrated for Pine nut but not for the other ingredients. Ten minutes after an oral challenge of a teaspoonful of Pine nuts, he developed marked conjunctival inflammation and periorbital itching and reddening. The IgE antibody level for Pine nut was Class 4.

Anaphylaxis to Walnuts and Pine nuts induced by ACE inhibitor has been documented.

A number of collections of case reports have further extended the understanding of the implications of Pine nut allergy.

In a study of Pine nut allergy, three case reports are given:

A 43-year-old female suddenly experienced anaphylaxis while eating in a Polynesian-style restaurant. SPT for common Oriental food ingredients were all negative. The chef disclosed that crushed Pine nuts were used in the salad. SPT with a Pine nut extract was positive within 3 minutes, and a 18 x 24 mm wheal, which featured pseudopodia and intense pruritus, had formed at 10 minutes. Contact with other sources of Pine, such as natural Pine resins, bark and needles, was not associated with any immediate or delayed respiratory, skin or other reactions in this patient.

The second case was of recurrent urticaria in a 28-year-old woman. She noted a spreading urticaria about an hour after eating a dish containing Pine nut. She was initially unable to identify the cause of this skin reaction, but about 5 months later, she had a recurrent and more severe urticarial episode, which she attributed to Pine nut. She was reluctant to be tested, but when a whole Pine nut was rubbed on her forearm, she developed erythema and a wheal, followed by a slightly scaly, rough, eczematoid eruption that lasted 3 or 4 days. Notable, she had consumed "2 or 3 glasses" of a resin-flavoured wine (Greek retsina, a white or rosé wine flavoured with Pine resin) without any reaction suggestive of allergy. External contact with Pine and other evergreen products did not appear associated with any clinical hypersensitivity in her case either.

The third case was of a 17-year-old male student with a history of multiple food sensitivity, including dermal, respiratory and gastrointestinal reactions to a variety of "nuts". Almond had caused "stomach upsets"; Peanut (and other legumes) were blamed for asthma-like symptoms, and Pistachio had reportedly caused stomatitis and epigastric pain. Skin reactivity for Pine nut was present, but an oral challenge "did not appear then - or subsequently - to be of any practical benefit to this multiply atopic individual". The authors nevertheless advised him to avoid Pine nut.

Severe anaphylaxis to Pine nut was described in 3 patients. A 28-year-old chef presented with generalised urticaria, swelling of the face, acute dyspnoea, and pulmonary collapse a few minutes after eating a salad dressing containing Pine nut. SPT for some tree nuts and Peanut, among other substances, were negative, but positive for Pine nut. Pine nut-specific IgE was 11 kUA/l. A second patient, a 35-year-old man who had presented with 2 episodes of anaphylaxis following ingestion of Pine nuts, reported that within minutes after ingestion, he had developed generalised urticaria, facial swelling, acute dyspnoea, and pulmonary collapse. He also reported generalised urticaria after eating Brazil nut. SPT was negative to a number of allergens, including Hazel nut, Almond and Peanut, and positive to Brazil nut, Chestnut, Walnut and Pine nut, among other allergens. Pine nut-specific IgE was 6.25 kUA/l and raised for Brazil nut and Chestnut. The third patient, a 19-year-old man, developed facial angioedema, acute rhinoconjunctivitis, and asthma rapidly after eating pesto sauce. He had previously experienced generalised urticaria after handling Pine nut. SPT was negative for Peanut and some tree nuts, except for Pine nut. The IgE antibody level was 79.9 kUA/l. None of the patients was Pine pollen-allergic.

Two further cases are also illustrative. A 23-month-old girl had during 3 months experienced moderate respiratory difficulty following ingestion of a small amount of Pine nut; she then experienced 2 episodes of angioedema of the eyelids, lips, face and feet. She had a third episode immediately after sucking Pine nuts: angioedema, wheezing and acute dyspnoea requiring emergency treatment. The patient tolerated normal food in her diet, including Almond, Walnut, Hazel nut and other nuts. A second patient, a 15-year-old girl, had at the age of 4 suffered severe urticaria, angioedema of the lips and eyelids, laryngeal oedema, hoarseness and dizziness after ingestion of a single Pine nut. At the age of 14, she had an episode of anaphylaxis, with vomiting, itching of the mouth, oedema of the tongue and larynx, general urticaria, severe respiratory difficulty, cyanosis and thoracic pain after eating a sausage that the authors suggest may have contained Pine nut. She tolerated Peanut, tree nuts and Sunflower seed. In both patients, SPT was negative to tree nuts and Pine tree pollen, but positive for Pine nut. Allergen-specific IgE for tree nut and Peanut were negative, and respectively 7 and 1.7 kUA/l, for Pine nut. Both girls were monosensitised.

Allergy to Pine nut has been described in a patient who showed no clinical symptoms to Pine pollen despite the presence in her serum of Pine tree pollen-specific IgE. SPT with fresh Pine nut and IgE antibody evaluation with Pine nut and Pine pollen extracts showed high levels of IgE against both. Immunoblotting experiments showed the presence in serum of IgE antibodies against several components of Pine nuts and pollen. Immunoblotting inhibition experiments demonstrated the presence of some cross-reacting components. This data confirmed the existence of food allergy induced by Pine nuts, but there were no symptoms of Pine pollen allergy. The authors suggest that the development of pollinosis may require a longer period of exposure to allergens but that, because of the cross-reactivity between Pine nut and Pine pollen extracts, co-sensitisation to these allergens could be possible. Similarly, a study reported on 3 individuals with Pine nut allergy and Pine pollen sensitisation.