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Reviewed: February 24, 2020
We have a patient with oral allergy syndrome to raw apples but not cooked apples. If the mother boils unpasteurized apple cider from a farm, will that make the cider safe for the patient to drink?


The simple answer to your question is yes, boiling or heating the cider would tend to denature the allergen responsible for the oral allergy or pollen food syndrome. According to one report that looked at specific temperatures at which the denaturation occurred (Bohle B, Zwölfer B et al. Cooking birch pollen-related food: divergent consequences for IgE and T cell-mediated reactivity in vitro and in vivo. J Allergy Clin Immunol 2006;118:242-249), apple changed at 90 degrees centigrade, which should be achieved with boiling. This paper suggested that 5 minutes of the heat would be required.

I have attached 2 prior Ask The Expert questions that provide detail concerning the syndrome.

Oral allergy syndrome; fruit-pollen syndrome; fruit-food syndrome
Q: 12/7/2013
I recently saw a 32 yo female who has allergic rhinitis who has a longstanding h/o oral tingling to various fresh fruits/vegetables. Over the last 20 yrs, the sxs have evolved to now mainly immediate chest tightness/wheezing to a large variety of uncooked fruits/vegetables and recently, even reactions to cooked fruits and possibly flour as well as raw egg. She is no longer sure what she can or cannot eat due to progressively increasing number of foods causing reactions. Benadryl resolves sxs w/n 20 min. Skin prick testing was positive to some culprit foods, but prick to prick testing to fresh foods was positive to all tested foods. Her serum tryptse is normal. CBC with differential is significant for 9% eosinophils (upper limit normal 5%). She denies a h/o underlying asthma and her rhinoconjunctivitis sxs are mild.

I have started her on Zyrtec, Singulair, and Ranitidine for now. She has Epipen and Benadryl for prn use. Do you have any suggestions on how to further evaluate this? Would allergen immunotherapy be of significant help with the food hypersensitivity sxs. Would doing a pre/post spiro (and if indicated, a trial of inhaled steroids) be helpful in decreasing the intensity/frequency of the reactions to foods?

A: Your patient has what has classically been referred to as oral allergy syndrome, which many authors refer to now as fruit-pollen syndrome or pollen-food syndrome. I have copied below for your perusal a number of excellent reviews of this topic, and I think you would also find a previous entry on our website very helpful by Dr. Dana Wallace.

I don't think any further studies would be helpful except the one that you suggested which would be a challenge with the food to which she attributes wheezing preceded by and followed by spirometry. Since she does not express any visible manifestations of an allergic reaction during this ingestion, it would be nice to document whether or not she is truly experiencing a fall in FEV1 or whether her shortness of breath might be related to anxiety.

Dr. Wallace's response was that systemic reactions can occur in patients with oral allergy syndrome, but are rare. On the other hand, since your patient exhibited positive skin tests to commercial extracts, it is possible that she is also reacting to acid stable/heat stable allergens as well. These would of course be more likely to exert a systemic response, but these responses usually would be accompanied by more manifestations than wheezing in a 32 year-old female (particularly cutaneous responses). Nonetheless, it is possible that her wheezing is a result of an IgE-mediated reaction to the foods, and documentation by spirometry would be helpful to discern whether or not this is occurring.

If it is occurring, then I believe a trial of inhaled steroids could be helpful. The only way to tell of course would be to initiate this therapy. However, long-term, daily use of inhaled steroids can reduce the severity of aeroallergen inhaled challenge, and therefore theoretically might be of help to your patient if her respiratory symptoms are IgE-mediated.

The issue as to whether or not immunotherapy is helpful in pollen-fruit syndrome is undecided.

There are several articles in the literature which have looked at whether or not immunotherapy has a beneficial effect on oral allergy syndrome. I have copied below a few references for your review.

I think that the most helpful of these may be the review by Mari, et al. in Current Opinion of Allergy and Clinical Immunology done in 2005. I have also included the abstracts of some original studies that have looked at this issue.

In my opinion, the last statement of the abstract of the Mari article describes the most appropriate opinion regarding the effect of immunotherapy at this time.

Food allergy and oral allergy or pollen-food syndrome.
Katelaris, Constance Helen:
Current Opinion in Allergy & Clinical Immunology. 10(3):246-251, June 2010
Purpose of review: This paper reviews current concepts in our understanding of oral allergy or pollen-food syndrome. As technology has improved, much more accurate profiling of food allergic individuals is now possible, resulting in more precise diagnosis, elucidation of cross reactivity patterns and more helpful prediction of risk of anaphylaxis.
Recent findings: The identification and characterization of various ubiquitous plant proteins have led to greater understanding of food cross reactive reactions. Newer diagnostic techniques utilizing purified and recombinant allergens are available for more precise diagnosis and clinical profiling of patients presenting with food allergy.
Summary: In-vitro screening of food allergic patients with large panels of allergens will change the accuracy of diagnosis resulting in better management. Allergens are now available for use in the allergist's office to improve diagnostic accuracy of skin tests in patients presenting with plant-food allergy. Knowledge of the specific sensitization of individual patients has consequences for both risk assessment and dietary management

Mol Nutr Food Res. 2004 Nov;48(6):441-8.
Food allergy to apple and specific immunotherapy with birch pollen.
Hansen KS, Khinchi MS, Skov PS, Bindslev-Jensen C, Poulsen LK, Malling HJ.
Allergy Clinic 4222, National University Hospital, Copenhagen, Denmark.
Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present

Curr Opin Allergy Clin Immunol. 2005 Jun;5(3):267-73.
The oral allergy syndrome: improved diagnostic and treatment methods.
Mari A, Ballmer-Weber BK, Vieths S.
Allergy Unit, National Health Service, Rome, Italy.
Purpose of review: The aim of this article is to review recent clinical and molecular findings related to the oral allergy syndrome in order to define its relevance in the field of food allergy, describe current diagnostic approaches and discuss attempts to use specific immunotherapy for treatment.
Recent findings: New allergenic sources causing the oral allergy syndrome have been reported. Their allergenic molecules have been identified. In most of those studies oral allergy syndrome is reported as a clinical manifestation among more severe ones. Some of the molecules generally considered not to be at risk for severe reactions have been demonstrated to pose a threat for inducing generalized reactions. Some studies tried to assess the usefulness of immunotherapy with birch pollen extract by either subcutaneous or sublingual routes for the treatment of associated food allergies. In most of the cases, a well-defined study design and a molecular approach at different study levels are lacking and thus the value of the obtained results is limited. To date, no final conclusion can be drawn on the basis of reported results.
Summary: The knowledge about the highly prevalent phenomenon of oral allergy syndrome is still incomplete, in respect to both, epidemiology and foods inducing symptoms. It is very important to reach consensus on several aspects of this food-induced allergic disease. Further studies are required to highlight whether immunotherapy using co-recognized inhalant allergens is an effective way of curative treatment, or if co-treatment with purified pollen-related food allergens will be required to obtain a long-lasting effect.

Clin Exp Allergy. 1998 Nov;28(11):1368-73.
Effects of birch pollen-specific immunotherapy on apple allergy in birch pollen-hypersensitive patients.
Asero R.
Ambulatorio di Allergologia, Ospedale Caduti Bollatesi, Bollate, Italy.

Allergy. 2003 May;58(5):435-8.
How long does the effect of birch pollen injection SIT on apple allergy last?
Asero R.
Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy.

Allergy. 2004 Dec;59(12):1272-6.
Comment in: Allergy. 2004 Dec;59(12):1269-71.
Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut.
Bucher X, Pichler WJ, Dahinden CA, Helbling A.
Division of Allergology, Department of Rheumatology and Clinical Immunology/Allergology, Bern, Switzerland

Phil Lieberman, M.D.

Heat labile versus heat stable allergens in foods cross-reacting with latex
Q: 4/5/2012
I have a patient with latex-fruit allergy. She posed a question to which I can't find an answer. With latex-fruit allergy, are the cross-reacting antigens in fruits/vegetables/nuts denatured by cooking, thereby allowing asymptomatic ingestion, as they are in pollen-food syndrome? In other words, does she have to avoid the foods if cooked? Her only reaction so far is with banana, and she was wondering about eating banana bread.

A: Unfortunately the answer to your question is not known, and in actuality depends upon the allergen in the food or foods responsible for the cross-reactivity. In many instances, latex-fruit syndrome is produced by heat and acid labile antigens, and these would be very unlikely of course to produce an anaphylactic event if the food was heated. However, even in the oral allergy syndrome (fruit-pollen allergy), in rare instances anaphylactic episodes have been recorded to the ingestion of fruits which previously produced only oral symptoms.

In addition, patients who are allergic to latex may have allergens to heat stable as well as heat labile allergens within a food, and this sensitivity may be independent of any cross-reactivity between latex allergens and food allergens per se since atopic individuals, as you know, are prone to make IgE antibodies against multiple allergens.

To illustrate this concept, since banana is the food in question, we can use it as an example. Bananas contain both heat labile and heat stable allergens that can cross-react with latex. A Class 1 chitinase, which is heat stable and which shares a hevein-related structure found in latex, can also be found in banana (as well as avocado and chestnut). This antigen is stable and heat resistant. If your patient has cross-reactivity between latex and banana based upon sensitivity to this antigen, she may well react to banana nut bread. In fact, banana is a very complex allergen and there are at least five well-defined allergenic moieties excluding the above mentioned chitinase. In a study of latex-allergic patients, 16 allergenic components were identified in banana. These allergens have molecular weights ranging from 17 to 128 kDa. Two of these were major allergens. One was of 33 kDa protein that was detected in 15 of 19 sera (88%), and there was also a 37 kDa detected in 13 of 19 sera (1). The 33 kDa allergen exhibited features of a chitinase which is a Class 1 antigen, and it had the hevein-like domain and, as noted, was a major allergen. It would be expected to be heat stable.

When one looks at the sera from latex-allergic individuals, 45% recognized 14 allergens in banana, and skin reactivity was found in 14 of 18 latex-allergic patients studied (2).

Thus we can see that the cross-reactivity between latex and banana can be related to a number of different allergens, some of which are heat stable and some of which are heat labile. Without component testing, we cannot tell in a given patient which allergens are responsible for the cross-reactivity.

Complicating this scenario is the fact that some individuals who initially expressed only oral allergy symptoms to banana can later experience anaphylaxis.

In summary, the majority of fruit and vegetable allergens cross-reacting with latex are probably heat labile, but there is always the possibility of cross-reacting with a heat stable allergen, and finally that there may be simultaneous allergy to non-cross-reacting antigens. Thus, if your patient has experienced a problem with uncooked banana, the only way to tell with a reasonable degree of certainty whether she might react to banana bread would be to do a graded oral food challenge.

Thank you again for your inquiry and we hope this response is helpful to you.
1) Delbourg MF, Guilloux L, Moneret-Vautrin DA, Ville G. Hypersensitivity to banana in latex-allergic patients. Identification of two major banana allergens of 33 and 37 kD. Ann Allergy Asthma Immunol 1996;76(4):321-6.
2) Alenius H, Makinen-Kiljunen S, Ahlroth M, Turjanmaa K, Reunala T, Palosuo T. Crossreactivity between allergens in natural rubber latex and banana studied by immunoblot inhibition. Clin Exp Allergy 1996;26(3):341-8.

Phil Lieberman, M.D.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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