Oral Allergy Sndrome (OAS)/ Pollen-Food Allergy Syndrome
July 27, 2004

Annie Khuntia, MD
Andrew Singer, MD

Background:  Since as far back as 1948, doctors have recognized that people with sensitivities to certain pollen also experienced oral symptoms such as itching and burning of the mouth associated with ingestion of various raw fruits including apples and nuts such as hazlenuts.¹  Studies conducted in the early 1980's found common epitopes between birch pollen and certain foods, confirming the association between birch pollenosis and sensitivity to a wide variety of fruits and vegetables.^2-4 

In 1987, Amlot et al coined the term "oral allergy syndrome" to describe this phenomena of oral symptoms associated with the intake of raw fruits, vegetables, nuts or all three, in a person with pollen sensitivity.⁵  Some controversy exists regarding this term because some authors use it to describe the association between inhalant pollenosis and food sensitivity, whereas others use the term to describe oral symptoms caused by any food allergen unrelated to pollen sensitivity such as peanut, tree nut and shellfish.  Because of this discrepancy food sensitivity associated with pollen is often termed pollen-food allergy syndrome.⁶

Etiology:  In food allergy where there is no pollen sensitivity, proteins in foods such as peanuts are able to sensitize and elicit and IgE mediated reaction after oral exposure.  In the case of peanut, this can only happen after primary sensitization has occurred by either peanut itself or a related food belonging to the legume family.⁷  This type of reaction is also referred to as a class I food reaction.⁸  Proteins in foods such as apples on the other hand, are typically not strong enough sensitizers to create an allergic response.  However, sensitization to homologous pollen proteins encountered through respiratory exposure, can mediate a reaction to cross-reacting proteins from a variety of fruits and vegetables (class II food allergy).  Pollen exposure is thought to be the initial source of sensitization in this form of food allergy.⁹  Therefore, unlike with class I food allergy, one can have a reaction to a food on first exposure.  These reactions are usually more mild than those described for class I food reactions, but can result in more serious reactions including anaphylactic shock.¹⁰  In a recent review of 1361 patients with food allergy and pollen sensitivity, 8.7% experienced systemic symptoms outside of the GI tract, 3% experienced systemic symptoms without oral symptoms, and 1.7% experienced anaphylactic shock.⁶  This form of food allergy is also known as pollen-food allergy syndrome.⁸

Pollen-food allergy syndrome represents possibly the most common food allergy in adults with 23-76% of patients with allergic rhinitis to pollen showing sensitivity to 1 or more foods.⁷  Among those with pollen-food allergy syndrome, upwards of 70% react to 2 or more foods.^11-13 

The most common pollenosis associated with pollen-food allergy syndrome is birch sensitivity.  People with birch sensitivity frequently react to fruits from the Rosacae family such as fresh apples, cherries, and peaches.  They can also react to nuts such as hazelnut and vegetables such as celery and carrots.¹⁵  Apple, which is part of the Rosacae family is one of the most frequent causes of pollen-food allergy syndrome.¹⁶  The major allergen in apple, Mal d 1, is structurally homologous to the birch pollen major allergen Bet v 1.¹⁷  It is an IgE mediated process caused by homologous pollen proteins cross-reacting with antigenic determinants from fruits, vegetables and nuts.  Over 70% homology in the primary sequence is generally needed for cross-reactivity to occur.¹⁴ In one study it was found that nearly all birch sensitive patients serum had detectable amounts of apple specific IgE, but not all patients had clinical sensitivity to apple.¹¹  In contrast when apple is the primary sensitizer, Mal d 3, a lipid transfer protein (LTP) is the primary allergenic component.¹⁸  People with sensitivity to LTP's usually do not have pollen sensitivity.  Lipid transfer proteins, are a family of 9 kD proteins which are widely distributed throughout the plant kingdom.^{19, 20}  They are expressed in the outer layer of plants and are though to possess antifungal and antibacterial properties. They have been found to be a major allergen in peach, apple, cherry, and plum and there is cross-reactivity between various LTP's. The proteins are found primarily in the peel of the fruit therefore, patients with mild reactions can often tolerate eating food items without the skin.  This is considered a class I food allergy and commonly causes a more severe reaction than those associated with pollen-allergy syndrome foods.²¹ Other common pollen-food allergy associations include ragweed, which cross-reacts with fruits such as banana, kiwi, and melon.  Mugwort, a type of weed, can cross-reacts with vegetables including celery and carrots. Grass allergy has also been associated with sensitivity to foods such as tomatoes, oranges, and a variety of melons.²²  Profilins, ubiquitous plant protein which regulates components of the actin cytoskeleton of plants, are the homologous proteins found in grass and associated foods.²³

Pathogenesis:  The symptoms and time course of pollen-food allergy syndrome are characteristic of a type I hypersensitivity, where allergen-specific IgE antibodies bound to mast cell surface Fce receptors are cross-linked by appropriate antigen, activating mast cells and subsequently releasing histamine.²¹  It has been suggested that pollen-food allergy syndrome is caused by a rapid response of mast cell-bound IgE, to allergens released from the raw fruit or vegetable as it enters the mouth.²⁴  There is believed to be a high concentration of mast cells in the oral and pharyngeal tissue secondary to continual exposure to pollen allergens in their inhalant form. 

Symptoms:  Factors which determine the clinical appearance of allergy in the face of sensitization are complex and relate to the hosts immune response, target organ hypereactivity, and the lability and digestibility of the allergen. Symptoms of pollen-food allergy syndrome are classically isolated to the oropharynx and can include localized lip, tongue, and oral mucosa swelling.  Additionally some can experience throat pruritus, angioedema, or both.^{16, 21}  People who experience symptoms, usually do so within a few minutes of eating the inciting food.  Almost all patients will experience symptoms within 30 minutes after contact with the offending food.²⁴ 

Cross-reacting proteins tend to be heat labile and it is thought that they can undergo rapid degradation in the GI tract.⁴ Because of the lability of the proteins, systemic reactions are unusual, but not unheard of.  Heating foods can also denature the labile proteins, making them less allergenic.^{4, 10}  People who demonstrate sensitivities to foods in their raw state therefore, can often tolerate the same foods after they have been cooked.  Additionally, the ripeness of the food can impact the allergenicity, with more mature foods having an increased potential to incite and allergic response when compared to less ripe foods.⁷  Risk factors for severe reactions included reactions to cooked foods, history of systemic reaction to one or more foods, positive skin prick test to commercial extracts, or an established allergy to peach.⁷ 

Diagnosis:  The evaluation of a patient with pollen-food allergy syndrome should start with a careful history to determine the triggering foods and the characteristics of the reaction.  Diagnostic tests usually begin with commercial extracts because they are readily available.  Testing done with commercial extracts are often negative because the responsible allergen can be easily destroyed during the manufacturing process.⁹  Prick testing with fresh fruits and vegetable, where the skin-testing lancet is first pricked through the skin of the food and then immediately used to prick the patient, is often the recommended test of choice because it has a higher sensitivity than commercial extracts. ^{21, 25}  RAST testing is generally less sensitive than prick-prick testing, but more sensitive than commercial extracts and can be used when fresh foods are not available.²¹  There is no role for intradermal testing in the diagnosis of pollen-food allergy syndrome.

Treatment:  If there has been a documented history of a systemic reaction and there is clinical or lab data to support, then the inciting food items should be avoided.  Additionally, self-injectable epinephrine should be prescribed.  Other factors that might indicate an increased risk of severe reaction include absence of pollen allergy and positive skin test to commercial extracts.⁶  For patients with mild pollen-food allergy syndrome, treatment should be individualized with the understanding that the risk of progression to a severe reaction is unknown.  Because many of the immunogenic proteins in fruits and vegetables are labile, for patients with non-life threatening reactions, cooked and canned food items may be an alternative.  Since many of the allergens are found in the skin of the food, some can avoid symptoms by eating food without skin.  However, peeling the food does not guarantee safety from a reaction because some immunogenic proteins are found in the flesh of the food as well.  Also, there is no way to avoid introduction of the peel into the flesh during the peeling process.²¹  Because of the unpredictable nature of the peeling process, especially in people with severe reactions peeling is not advocated.  The only safe alternative for this population is strict avoidance. 

Since pollen-food allergy syndrome is due to cross-reacting allergens, it has been suggested that immunotherapy may have potential therapeutic benefits by alleviating the allergic rhinitis symptoms as well as improving the food allergy associated symptoms.^{16, 26, 27} 

Although much has been discovered about pollen-food allergy syndrome since it was first recognized 70 years ago, further studies are necessary to further define the clinical features and the natural progression of the disease.  Additionally, the development of improved diagnostic testing is necessary to develop a more specific approach for the diagnosis and management of patients with pollen-food allergy syndrome.

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