Q:

1/23/2015  
I have been surprised at the lack of primary in the allergy literature regarding clinical cross-sensitization and cross-reactivity with seed allergies, especially in the age of component resolved diagnostics. For patients presenting with a seed allergy, I find negligible data on clinical cross-reactivity to other seeds which might have homologous seed storage or other shared seed proteins. Many foods have seeds in/on the foods, I find it nearly impossible to provide guidance to patients. I have found here to be the best repository of data for this question, but most of the cross-reactivity data is with regards to aeroallergens and legumes. I was hoping perhaps the experts might know of more data unbeknownst to me or be able to survey present clinical practices at major centers of excellence in food allergy.

A:


I think your summary of the literature suggesting that we do not have a great deal of detail on the cross reactivity of ingested seeds is a fair assessment. The 2S, 7S, 11S storage proteins are common to many seeds and could provide cross reactivity. However, the clinical evidence of the importance of this cross-reactivity is not well substantiated. Poppy and sesame and mustard and sunflower may cross react (see below). I searched the Allergome data base and the information I found was related to inhalant allergens, as you indicated.

In summary, I am not able to help you in your advising patients except the concern about poppy and sesame and possibly mustard and sunflower.

Allergy to seeds
Q: 11/30/2011
What is the current data regarding cross-reactivity of seeds (sesame, mustard, sunflower, and poppy)? If a toddler has a history and testing positive for an allergy to one seed, should testing for other seed allergies be considered? How accurate is ImmunoCap blood testing for seeds?

A: I am going to preface my answer to your question with a quote from Dr. Sicherer's superb and comprehensive article on the clinical significance of cross-reactivity between foods, which is:

"Reactions to seeds, such as sesame, mustard, and poppy, are reported (27, 35, 36) and
cross-reactivity with foods (hazel, kiwi, and other seeds) and pollens is potentially important, but the full clinical implications are far from established. (27). Vocks E, Borga A, Szliska C, Seifert HU, Burow G, Borelli S. Common allergenic structures in hazelnut, rye grain, sesame seeds, kiwi, and poppy seeds. Allergy 1993;48:168-72. (35). Asero R, Mistrello G, Roncarolo D, Antoniotti PL, Falagiani P. A case of sesame seed-induced anaphylaxis. Allergy 1999;54:526-7. (36). Rance F, Dutau G, Abbal M. Mustard allergy in children. Allergy 2000;55:496-500" SOURCE: Sicherer SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001; 108(6):881-890.

This article, even though written in 2001, still remains a valid source of information, and according to my search of the literature, very little has been added to the literature regarding this subject since that time.

A slightly more recent review on cross-reactivity to food (van Ree, R. Clinical importance of cross-reactivity in food allergy. Current Opinion in Allergy and Clinical Immunology 2004; 4:235-240) also had very little to say on this subject, mentioning only the following in regards to cross-reactivity between seeds:

"Seed storage proteins 2S, 7S and 11S: limited level of cross-reactivity between foods? Seed storage proteins 2S albumin, 7S vicilin and 11S legumin have been identified as the major allergens in legumes like peanut, soy [52.,53,54] and lentils [55.], but also in tree nuts [56..,57.] and other seeds like sesame [58.] and sunflower [43,59.]."

As you can see from these two reviews of cross-reaction between foods, there are little clinically significant data that would allow us to answer your question definitively.

However, there are some in vitro studies which have looked at allergens contained in seeds from the standpoint of their potential cross-reactivity. I will share with you what I have been able to find in this regard.

Perhaps the largest body of literature looking at the seeds mentioned relates to sesame seed. In vitro cross-reactivity between sesame and a number of other foods has been demonstrated. In terms of seeds, sesame has been shown to cross-react with poppy seed (1). Three patients who experienced IgE-mediated reactions to poppy also showed positive serologic testing to sesame.

I might mention parenthetically that sesame seed has been shown to cross-react with other foods including kiwi, rye, hazelnut, black walnut, macadamia, cashew, pistachio, and peanuts.

Thus, I think it is safe to say that there is potential cross-reactivity between poppy seeds and sesame seeds. As with sesame, poppy seeds have also shown serologic reactivity to other foods including kiwi, hazelnut, and rye grain, and poppy seeds have homologs of BET v 1 and profilin, and shows cross-reactivity to birch, mugwort, and grass pollen.

I could find very little information on cross-reactivity between sunflower seeds and other seeds, but there may be cross-reactivity between sunflower seed and mustard seed (2). Sunflower seeds do show cross-reactivity with other members of the compositae family such as mugwort aeroallergens.

From the above, the best I have been able to conclude therefore is that poppy seed and sesame seed have been shown to have cross-reactivity, and mustard seed and sunflower seed have been shown to have cross-reactivity in limited studies.

As far as I can discern from a literature search, this is all the information we have available. Therefore, no definitive recommendation, at least in my opinion based on these data, can be made at this time to answer your questions specifically. However, I would certainly consider the possibility of reactivity to other seeds in the toddler that you described.

I have not been able to find any information on the sensitivity/specificity of ImmunoCap for testing for seeds. However, all of these seeds are available by ImmunoCap, and based on the performance with other aeroallergens, I would assume that the specificity and sensitivity of this test for seeds is good. Skin testing has also been done for these seeds as well.

As I mentioned at the beginning of my response, one of the best reviews of the clinical significance of cross-reactivity was written by Dr. Scott Sicherer, who is an internationally known expert in this area. I have shared with you the information that I have found available, but because I could not give you a definitive answer, I would like to get Dr. Sicherer's input on this inquiry. Therefore I am forwarding your question along with my response to Dr. Sicherer for his further comments.

References:
Gloor M, et al. Poppy seed anaphylaxis. Scheiz Med Wochenechr 1995; 125(30):1434-1437.
Asero R, et al. Allergenic similarities of 2S albumins. Allergy 2002; 57(1):62-63.

Response from Dr. Scott Sicherer:
I substantially agree with your comments. Basically, being allergic to one seed does not strongly suggest that there will be allergy to others, but we often find ourselves testing when the history is unclear. Certainly, we may approach it differently when we are simply looking at a positive test versus a person who actually already had anaphylaxis to a seed and has not eaten some other seeds already. There are recent references that give some insight on the “accuracy” of sesame tests, basically the results are not that helpful and food challenges are often needed. Just to complicate things further, negative tests have been noted in people with clear reactions to sesame and this is probably caused by some oil-based allergens, a topic also recently addressed in a paper I pasted below.

Sesame Allergy: Role of Specific IgE and Skin Prick Testing in Predicting Food Challenge Permaul P, Stutius LM, Sheehan WJ, Rangsithienchai P, Walter JE, Twarog FJ, Young MC, Scott JE, Schneider LC, Phipatanakul W.
J Allergy Clin Immunol. 2009 Feb;123(2 Suppl 1):S24. No abstract available.

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy.
Maloney JM, Rudengren M, Ahlstedt S, Bock SA, Sampson HA.
J Allergy Clin Immunol. 2008 Jul;122(1):145-51. Epub 2008 May 27.

Diagnosing IgE-mediated hypersensitivity to sesame by an immediate-reading "contact test" with sesame oil.
Alonzi C, Campi P, Gaeta F, Pineda F, Romano A.
J Allergy Clin Immunol. 2011 Jun;127(6):1627-9. Epub 2011 Mar 5. No abstract available.

Scott H. Sicherer, MD
Professor of Pediatrics
Jaffe Food Allergy Institute
Mount Sinai School of Medicine
New York, NY

Sincerely,
Phil Lieberman, M.D.

Possible allergic reaction to lotus seed
Q: 5/23/2013
I recently saw a toddler who developed peri-oral hives and lip swelling after eating a taiwan-made, Korean cereal bar. The bar contained: brown rice, lotus seed, barley, buckwheat, oat, peas, mung bean, red beans, black beans, soy and egg. Skin testing to the cereal bar was positive, but tests to barley, oat, tree nuts, sesame were negative. She eats rice, barley, buckwheat, oat, pea, and many types of legumes on a regular basis. The 2 ingredients that I could not confirm ongoing exposure to are mung bean and lotus seed. She regularly eats soy and other legumes, so my suspicion is with lotus seed. What can you tell me about possible lotus seed allergy? Does it cross react with any other seeds? Lotus seed is used in cultural foods consumed by this family, so it would be helpful if I could offer them additional guidance. Thank you.

A: Unfortunately, I am not sure that I can be of help. I have never personally seen a reaction to lotus seed, and a search of the literature failed to reveal a single case. In addition, I could not find any in vitro tests for specific IgE to lotus seed or any article describing its allergens or potential cross-reactivity with other foods. The only thing that I can suggest to you to confirm lotus as the responsible allergen is to purchase the seeds and perform a prick-to-prick test with them.

However, because I could find nothing to help you, I am contacting Dr. Scott Sicherer, who has a special interest in pediatric food allergy, to see if there is knowledge with regard to your question that I could not find. Dr. Sicherer is a nationally recognized expert in food allergy and has published in cross-reactivity of food allergens.

Response from Dr. Scott Sicherer:
After Google and Pubmed searches I have nothing really to add. It appears to be a very commonly used seed (sometimes called a nut) for food and medicinal uses. It is hard to imagine allergy would not be "possible" and one internet comment warns about possible allergy. I do not see work on allergen characterization (cross reactivity). I could not find it on Allergome. Obviously, allergy to this food is not "common" unless reports are buried in non-English sources. There are case reports of all sorts of allergic reactions to various fruits, seeds, etc., that are not in our western mainstream diet and so the doctor may want to continue her evaluation and write a case report.

Sincerely,
Phil Lieberman, M.D.

I regret I could not find additional information to help you.

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

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