Q:

9/27/2012
I have a patient that has had anaphylaxis (generalized hives, SOB, and feeling her throat was closing) on three separate occasions after having cherries, a strawberry, and grapes. The first two reactions occurred within 30 minutes and were treated in the ER. The last reaction occurred 2 1/2 hours after having grapes. She can tolerate wine however. RAST tests and skin tests were positive for these fruits and several other fruits with similar structures. I have told her to avoid fruits for now. What else can I do to help her? Thank you for your advice.

A:

Thank you for your inquiry.

Unfortunately, as you know, the only true treatment of food allergy as described in your patient is avoidance of the foods in question. On the basis of your description, therefore, I believe it will be necessary for her to avoid all three of the foods to which she reacted. I do not think there is any other safe option for her unless you wish to test the validity of these reactions by doing an oral challenge. Based upon the history, however, at least in my opinion, the events were highly likely to have been due to the cherries, strawberries, and grapes ingested prior to the respective episodes. Therefore the only question is whether she is at risk of responding to cross-reactive, related foods. This cannot be answered definitively without oral challenges, and therefore the best we can do is simply look at what is known about cross-reactivity regarding these foods based upon published literature.

I will do my best to summarize this knowledge for you, but once again, the only definitive way to conclude whether or not your patient will react to cross-reacting foods is via an ingestion challenge.

Nonetheless, we will look at each food independently and try to give you some perspective regarding potential cross-reactivities.

Cherries are members of the Rosaceae family. Several cherry allergens have been isolated. They are Pru av 1, 2, 3, and 4. Pru 1 is a Bet v 1-homologue. Pru 2 is a thaumatin-like protein. Pru 3 is a lipid-transfer protein. And Pru 4 is a profilin.

There are a number of potential cross-reactivities between cherry and other foods. In regards to Pru av 1, there is potential cross-reactivity with similar allergens in apple, pear, celery, peach, and carrot. However, this cross-reactivity may be more related to oral allergy syndrome rather than systemic reactions.

Perhaps of more importance is the fact that Pru av 2 has been found to be similar to thaumatins in grape and apple.

Pru av 3 has shown to be similar in structure to allergens found in peach and apricot, and perhaps in grape, hazelnut, and apple.

Things get even more complex in regards to lipid-transfer proteins in cherry. There is a wide range of potential cross-reactivities. These include hazelnut, blueberry, raspberry, asparagus, and carrot.

In regards to the profilin family, once again there are complex interactions and some potential cross-reactivity with celery, pineapple, banana, carrot, and pear.

As you can see, it is hard to make “sense” of all these potential cross-reactivities in regards to their clinical significance. However, a couple of references might shed some light on this issue (1, 2). This may be of particular importance to your patient because it concerns clinical cross-reactivity with grapes, the probable cause of one of her reactions.

In one of these studies, approximately 48% of patients with a history of allergic reactions to grapes or their products were cosensitized to cherries, and about 33% were cosensitized to strawberries (1).

In another study also involving patients with allergic reactions to grapes, approximately 19% also showed potential cross-reactivity with cherry (2).

Thus, there is at least some clinical confirmation that your patient reacted to an allergen common to cherries and grapes. This cross-reactivity has also been reported in an individual who had oral allergy syndrome to grapes, and showed skin test reactivity to cherry as well (3).

Grapes are a member of the Vitaceae family. There have been five major allergens isolated from grape, and they include a lipid-transfer protein, a profilin, a thaumatin, endochitinase, and a glucanase. Thus, as you can see, there are potential cross-reactivities between grapes and cherries in terms of the allergens that have been isolated from each.

Unfortunately, there is also a very complex history of cross-reactivity between grapes and other foods. There is good evidence that grapes will cross-react with a number of members of the Rosaceae family. Evidence exists for cross-reactivity with peach, tree nuts, mustard, mulberry, cabbage, figs, kiwi, bananas, melon, and other foods in terms of the lipid-transfer protein contained in grapes. However, the clinical significance of these cross-reactivities has not been clearly established.

Strawberries also are members of the Rosaceae family. When one looks at the allergens in strawberries, it is obvious that there are very clear potential cross-reactivities. These allergens consist of a Bet v 1 homologue, a profilin, and a lipid-transfer protein. Therefore, it is obvious that cross-reactivity can exist with both grapes and cherries.

When one enumerates potential cross-reactivities that have been evaluated, as in grapes, the foods are almost too numerous to list. Once again, however, the clinical significance of these cross-reactivities is not clearly established, and many of them are probably related to potential for cross-reactivity regarding oral allergy syndrome (pollen-food) cross-reactivity.

We have already mentioned that strawberry can cross-react with grapes, and since members of the Rosacea family often cross-react with one another, clearly there is potential that strawberries and cherries can cross-react as well (4).

As previously mentioned, it is extremely difficult, if not impossible, to make any clear-cut clinical decisions based on these complex immunologic cross-reactivities. Perhaps the best attempt to do so is Dr. Scott Sicherer’s article in the Journal of Allergy and Clinical Immunology that was published in 2001 (5). Dr. Sicherer, in this article, has a section entitled “Diagnosis and Management” in which he discusses the clinical approach to patients with potential reactions to foods which cross-react with one another. And, as noted above, he states that, “The oral food challenge remains the only modality to identify true clinical reactions.” He also states, “Unfortunately, the clinician could be facing an enormous number of oral challenges with potentially severe reactions. In practical terms many patients will not undergo oral challenges but may maintain diets arrived at through their clinical history, reasoning on the basis of the available literature, and the results of tests for specific IgE antibodies.”

I believe that this article is worth your review to get a further perspective from Dr. Sicherer regarding this clinical approach.

There is an excellent table and figure which helps guide clinical decisions. These are too complex to discuss in detail here, but I will mention to you what he states about the Rosaceae family: “Established allergy to any one Rosaceae family food increases risks. Some members are less problematic (e.g. pear), and others are more problematic (e.g. peach).”

In summary, your patient represents a difficult clinical problem which we all encounter, and there is no definitive way for you to solve the issues involved. What does appear apparent, however, is your patient appears to be reacting to allergens common in the foods incriminated as responsible for her three reactions. They should, of course, be avoided, and foods with potential cross-reactivities can only be evaluated by oral challenge.

In my experience, over time, the patient, as Dr. Sicherer mentions in his article, develops a guarded diet oftentimes decided upon by food preferences and trial and error experimentation. If, however, you wish to further assist them in this regard, you can pick a few selected fruits which they have eaten in the past without difficulty, and perform graded oral challenges in-office.

Thank you again for your inquiry and we hope this response is helpful to you.

1. Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27(1):68-71.
2. Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, Papasteriades CA. Grape anaphylaxis: a study of 11 adult onset cases.
3. Giannoccaro F, Munno G, Riva G, Pugliese S, Paradiso MT, Ferrannini A. Oral allergy syndrome to grapes. Allergy 1998;53(4):451-2.
4. Yman L. Botanical relations and immunological cross-reactions in pollen allergy. 2nd ed. Pharmacia Diagnostics AB. Uppsala. Sweden. 1982: ISBN 91-970475-09.
5. Sicherer SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001; 108(6):881-890.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology