Q:

9/5/2013
I recently evaluated a 2 year-old female with history of contact urticaria following all milk/milk-product contact. She had been strictly avoiding all milk due to this history. Skin prick testing was equivocal and serum specific IgE was essentially undetectable at 0.35 ku/L. Subsequently, she successfully passed/tolerated oral milk challenge ingesting >8-10 grams of 2% milk without any immediate of delayed reaction. Milk was reintroduced into her diet without any obvious systemic reaction/symptoms. Of interest, however, every time she has direct milk protein skin contact (milk, ice cream, yogurt) she develops localized urticaria only. I assume that this is a non-immunologic contact urticaria (non-IgE mediated) as she has tolerated oral ingestion without reaction. Based on prior studies, this may be related to polyamines in the food substance. Is there a specific testing modality for this? Does this history warrant continued avoidance?

A:

Thank you for your inquiry.

I believe the reaction to yogurt can be explained by its acidity and histamine content. Please the below question and reply posted on 7/9/2012.

Contact urticaria to yogurt in the absence of detectable specific IgE to milk
7/29/2012
Q: Recently I saw a 9 month old infant who would develop perioral hives when given yogurt and erythema if yogurt is dropped on her skin though she tolerates 4 oz of Similac advanced with impunity and a negative skin test to milk though an immunocap to milk was not obtained; what additional diagnostic steps would you recommend to exclude milk and yogurt allergy? Your advice is greatly appreciated.

A: Thank you for your inquiry.

I cannot answer your question with complete confidence, but I can perhaps share some light on the issue. First of all, I would like to refer you to a similar question which was submitted to our website and answered by Dr. Michael Blaiss. It involved contact urticaria to ranch dressing and tomato sauce in a toddler.

For your convenience, I have copied below the previous question along with the response from Dr. Blaiss. As you can see, the response to this inquiry explains such contact urticaria in the absence of specific IgE to the food in question might have been due to the histamine content of the food.

The contact urticaria in your patient could well be due to the same cause. Yogurt, as you can see from two of the abstracts which are copied below (one of these does not have the reference because it was a Korean journal and the title was printed in Korean), contains a significant amount of histamine. In addition, lactobacilli contain amine decarboxylase enzymes which are capable of producing histamine.

Additionally, yogurt is of low PH (4 to 5 or lower), and this relatively acidic PH could also perhaps explain a local contact urticaria.

Having said this, the only definitive test, as you know, for food allergy is a controlled feeding. Once you have done tests for specific IgE, I know of no other method to investigate whether or not a patient truly is at risk for an IgE-mediated event to a food.

Thus, in my opinion, the most plausible explanation for the reaction to yogurt in your patient is the one which is described in the response below, but as noted, I know of no other way to discern whether this is correct other than a graded food challenge.

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

Screening selected strains of probiotic lactic acid bacteria for their ability to produce biogenic amines (histamine and tyramine)

International Journal of Food Science & Technology
Volume 46, Issue 10, pages 2062–2069, October 2011
Summary
The aim of this study was to investigate the production of biogenic amines (BA), histamine and tyramine by some probiotic lactic acid bacteria (LAB). Fifteen strains representing six LAB species were screened qualitatively by growing them in a decarboxylase medium. Quantitative analysis was carried out by HPLC analysis with direct derivatization of acid extracts. Lactobacillus casei (TISTR 389) and Lactobacillus delbrueckii subsp. bulgaricus (TISTR 895) were found to produce BA. The highest levels of histamine (1820.9 ± 3.5 mg L−1) and tyramine (5486.99 ± 47.6 mg L−1) formation were observed for the TISTR 389 strain, while TISTR 895 produced only histamine (459.1 ± 0.63 mg L−1) in the decarboxylase broth. Biogenic amine potential was not observed for the Lactobacillus acidophilus, Lactobacillus lactis subsp. lactis, Lactococcus lactis subsp. lactis, and Lactobacillus plantarum strains studied. This study confirmed that BA formation is strain dependent and not related to the species. Therefore, careful screening for amino acid decarboxylase activity is recommended before selecting LAB as appropriate starter or probiotic strains in food and dairy industry.

Analysis on the Contents of Histamine in Korean Foods
The purpose of this report is to present a list of Korean foods containing histamine, that is known to cause food allergy and chronic urticaria. For the measurement of histamine in foods, the application of spectrofluorimeter is used. Among the food groups, sea foods (mackerel, pacific saury, spanish mackerel, anchovy, hair tail, tuna) contain most high amount of histamine, and the contents of see weeds (sea mustard, laverare) are also high. Milk and milk products (mozzarella cheese, yogurt) contain more histamine than animal meats. Plant foods like cereals, vegetables or fruits contain much less histamine than other food groups, except spinach. The contents of dried sesame, sesame oil, and mugicha, green tea, ginseng tea, mayonnaise, tomato ketchup are relatively high. This paper will be used as a fundamental guideline in planning dietary management of allergy and for the operational plans for the future nutrition education intervention. Because the foods rich in histamine may cause allergy-like syptoms, it may be required to label the foods containing histamine.

Biogenic Amines and Polyamines in Milks and Cheeses by Ion-Pair High Performance Liquid Chromatography J. Agric. Food Chem., 2000, 48 (11), pp 5117–5123
Abstract
The proposed chromatographic method provides a complete resolution of twelve amines in a single run in milks and unripened cheeses, avoiding the losses of resolution linked to fluctuations in working temperature. We also propose an alternative chromatographic gradient, which can be useful for samples that have undergone long ripening periods, like ripened cheeses. According to the results of the reliability study, the method described was precise, accurate, and sensitive. The method was applied to several samples of milks and cheeses and the results showed that the biogenic amine profiles varied greatly, not only between different types of samples but also among the samples from the same kind of products. In unripened cheeses, milks, and yogurts, spermidine and spermine were the prevailing amines, but in ripened cheeses the major amine was tyramine, followed by putrescine and cadaverine.

Contact urticaria and rash due to tomato sauce and ranch dressing
Question:
I commonly see children with a history of contact rashes (no other symptoms) with tomato sauces and ranch dressing (skin tests negative for relevant food allergens). I have not been able to locate any handouts/information to give to these parents. Are you aware of what ingredient/component of these foods is causing the contact rash and is there any information/handout I could give to the families?

Initial response from Dr. Lieberman:
Unfortunately, I personally have not encountered the phenomenon you describe, and am not aware of any information in this regard. In addition, an online search for information also failed to produce any relative information. However, in case I have simply missed something, I am going to ask the same question of Dr. Michael Blaiss, who sees a much larger pediatric patient population. If he is aware of any information in this regard, I will of course forward that to you immediately.

Thank you again for your inquiry and once again, I will keep you posted as soon as I hear from Dr. Blaiss.

Response from Dr. Michael Blaiss:
I see this commonly in toddlers. I believe that this is a local reaction to histamine in foods and/or histamine releasing substances in foods. Spinach and tomatoes are high in histamine which explains such foods such as tomato sauce. In addition, while citrus fruits are not themselves considered high in histamine, they can release histamine in the body from mast cells which is of a non-IgE mechanism. Also ranch dressing is a major culprit of this local reaction. I don't know for sure the cause, but I wonder if this is a local reaction to dill weed in the dressing or preservatives in the dressing. The good news is all most all children "out grow" this condition. I'm not aware of any patient handouts on this condition.

Sincerely,
Michael S. Blaiss, M.D.

It is also true that polyamines are present in milk, and they can, at least in vitro, cause histamine release (Allergy. 1991 Jul;46(5):349-54).

But I could find no reference to their causing contact urticarial to milk. So I am referring your inquiry to Dr. Anna Nowak-Wegrzyn, who is an internationally recognized expert in food allergy and specifically allergy to milk. When we receive Dr. Nowak-Wegrzyn’s response, we will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Anna Nowak-Wegrzyn. Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Anna Nowak-Wegrzyn:
It is not uncommon among our pediatric patients to have contact skin reactions to milk/milk products and no symptoms upon ingestion. These are usually the children who had milk allergy and are now close to outgrowing it. The patient described fits this profile, she has a very low but detectable milk-IgE level of 0.35 and equivocal skin test to milk. I am assuming that the prick skin test was done with a commercial extract of milk; I suspect that skin prick testing with raw milk would yield a stronger positive reaction. My impression is that this child has an allergic contact urticaria to one of the milk proteins, not to polyamines. I am not familiar with testing for polyamine reactivity. My practice is to continue milk/dairy ingestion without restriction in such children.

Kind regards,
Anna Nowak-Wegrzyn, MD
Associate Professor of Pediatrics
Icahn School of Medicine at Mount Sinai
Jaffe Food Allergy Institute

AAAAI - American Academy of Allergy Asthma & Immunology