Q:

1/7/2014
I have a patient who reports allergy to beef, with symptoms of abdominal pain, cramping, and diarrhea when eating beef products. She stopped eating beef 12 years ago. Since then she has experienced symptoms of throat-closing sensation on multiple occasions when exposed to the smell of cooking or cooked beef in restaurants, but has never experienced any pruritis or urticaria.

She has been advised not to receive shingles vaccination, because the vaccine contains trace amounts of bovine calf serum.

Her prick test is negative to beef.

1. Are you aware of any reports of aerosolized bovine serum albumin causing anaphylaxis (analogous to what has been reported with shellfish)?
2. Is there any data regarding administration of Zostavax to individuals with IgE-mediated sensitivity to beef?

A:

Thank you for your inquiry.

Clearly, bovine serum albumin can be allergenic, and respiratory reactions have been reported to bovine serum albumin powder. However, I was not able to find any report of respiratory reactions to beef fumes from cooking. This does not mean such could not occur, but I was not able to find any reports in the literature describing respiratory reactions to cooking/cooked beef.

In answer to your second question, anaphylactic reactions have been reported to Zostavax. This is noted in the package insert. At least on one occasion they have been attributed to gelatin, but the gelatin moiety is porcine, and not bovine. To my knowledge none have been to bovine albumin.

The above are the best direct answers that I can give you to your questions. However, parenthetically, I should note the following.

In my opinion, it is quite likely that your patient could take zoster vaccine without difficulty. In addition, I believe you could carry out further studies which could better refine the likelihood of a reaction. The reasons I feel that it is likely that the patient could take the vaccine are as follows:

There are questions regarding the major allergen in beef, but clearly, as you can see from one of the abstracts copied below, bovine serum albumin may not be the allergen to which she has reacted. Bovine gammaglobulin is a major allergen, and the bovine serum albumin of beef is heat labile. Heating has a tendency (although not universal) to diminish its allergenicity. In addition, milk contains 1% bovine serum albumin at a concentration of 0.1-0.4 grams/L. Beef contains the same bovine serum albumin. If she was allergic to bovine serum albumin sufficiently to react to trace amounts, I would assume she would be having problems with milk as well. Finally, she has a negative skin test to beef.

Based upon these observations, as mentioned, I think it is unlikely that she would react to the zoster vaccine. However, it would not be difficult to further assess her sensitivity by doing the following:

1. Obtaining a serum specific IgE to beef.
2. Testing "prick to prick" to cooked and fresh beef.
3. Testing "prick to prick" to fresh milk, and consider obtaining a serum specific IgE to milk (you would be testing to bovine serum albumin).

Bovine serum albumin can be purchased in small amounts for a reasonable cost. You can find purchase sites online by simply Googling "purchase bovine serum albumin." The articles reported in abstract below contain concentrations of bovine serum albumin used to skin test. You could order bovine serum albumin and use the protocol described in these articles to skin test your patient.

Finding negative results with these tests would give you great assurance that she would not react to the bovine serum albumin contained in Zostavax.

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

Severe anaphylactic reaction to bovine serum albumin at the first attempt of artificial insemination Allergy Volume 50, Issue 2, pages 179–183, February 1995.
A 33-year-old woman without history of previous atopic diseases or drug allergies developed a severe anaphylactic reaction with asthma, vomiting, itching, generalized urticaria, and angioedema during artificial insemination with her husband's sperm. The sperm-processing medium contained bovine serum albumin (BSA). Skin prick test and RAST demonstrated an IgE-mediated hypersensitivity to BSA as well as a polyvalent atopic sensitization to pollens, animal danders, cow's milk, beef, pork, and mutton. SDS—PAGE studies indicated serum albumin to be the appropriate allergen with a high degree of cross-reactivity between serum albumin from different animal species. Artificial insemination with fluid containing potential allergens can, therefore, represent an unnecessary risk for atopic females, even in the absence of prior clinical symptoms of allergic diseases. Preoperative testing with the medium is recommended.

Eur Ann Allergy Clin Immunol. 2013 Aug 1;45(4):144-7.
Bovine Serum Albumin: a double allergy risk.
Voltolini S, Spigno F, Cioè Et Al A.
Author information
Abstract
We analyse two cases of Bovine Serum Albumin (BSA) allergy. The first regards a female laboratory technician with a history of bronchial asthma due to cat allergy, who developed an exacerbation of bronchial symptoms as a consequence of BSA powder inhalation at work. To date, sensitization to BSA as a cause of occupational asthma has rarely been reported in the scientific literature. The second case concerns a woman with a similar cat sensitivity, who presented an oral allergy syndrome-type clinical reaction, gastric pain and diarrhoea immediately after eating cooked pork meat. Subsequently, she developed the same reaction after eating goat meat and goat cheese, and then also after eating beef. Both patients resulted specifically sensitized to BSA and to other mammalian serum albumins which play a role as panallergens in animals. The two cases show that BSA, a well known cause of food allergy in childhood, may also provoke symptoms of food allergy in adulthood, though in case of powder inhalation, it may provoke respiratory symptoms. Prior animal sensitization appears to represent a risk factor.

Pediatr Allergy Immunol. 2007 Sep;18(6):503-7.
Sensitization to serum albumins in children allergic to cow's milk and epithelia.
Vicente-Serrano J, Caballero ML, Rodríguez-Pérez R, Carretero P, Pérez R, Blanco JG, Juste S, Moneo I.
Author information
Department of Allergology, Hospital General Yagüe, Burgos, Spain.
Abstract
Patients with persistent milk allergy and specific immunoglobulin E (IgE) to bovine serum albumin (BSA) have a greater risk of rhinoconjunctivitis and asthma because of animal dander. To prove the cross-reactivity between serum albumin (SA) of different mammals in milk, meat, and epithelia and determine if heat treatment of meats decrease the allergenicity of albumins. The study was performed using SDS-PAGE and IgE-immunoblotting using sera from eight patients sensitized to milk, BSA, and animal danders. Sera from non-allergic and only animal dander allergic subjects served as a control. With one exception, all patients' sera recognized SA in different meats (beef, lamb, deer, and pork), epithelia (dog, cat, and cow), and cow's milk. Some patients even were only sensitized to SA in meat and epithelia. Danders' allergic only recognized other proteins in epithelia but not SA. No patients reacted to SA from heated meat extracts. Serum albumin is an important allergen involved in milk, meat, and epithelia allergy. The first contact with SA was through cow's milk and patients developed sensitization to epithelia SA even without direct contact with animals. Patients with both BSA and cow's milk allergy must avoid raw meats and furry pets.

Heat treatment modifies the allergenicity of beef and bovine serum albumin AllergyVolume 53, Issue 8, pages 798–802, August,1998 The effect of heat on the allergenicity of beef and bovine serum albumin was investigated among 10 toddlers skin prick test (SPT)-positive to raw and cooked beef. The meat-allergy diagnosis was confirmed during double-blind, placebo-controlled food challenge (DBPCFC) with 180 g of beef cooked for 5 min at 100°C. SPT with homogenized and freeze-dried beef, and heated and unheated bovine serum albumin were performed. Both heated and unheated bovine serum albumin, homogenized beef, and freeze-dried beef were used in trial DBPCFC. All children were SPT-positive to unheated bovine serum albumin. Seven were positive to heated bovine serum albumin, one to freeze-dried beef, and none to homogenized beef. DBPCFCs were negative for homogenized beef and freeze-dried beef, positive for unheated bovine serum albumin in five patients, and positive for heated albumin in four children. We conclude that heating reduces sensitization to beef and bovine serum albumin but does not abolish reactivity to albumin under home conditions. However, industrially heat-treated and sterilized homogenized beef and freeze-dried beef may be suitable substitutes in beef-allergic children's diets.

Meat Allergy: Investigation of Potential Allergenic Proteins in Beef Bioscience, Biotechnology, and Biochemistry, Vol. 64 (2000) No. 9 P 1887-1895 The potential allergenic proteins in beef were investigated. The sera of ten beef-allergic patients suffering from atopic dermatitis and having a positive RAST score to beef, aged 3-18 years, were obtained from Yoshida Hospital in Japan, and five non-allergic individuals were subjected to this study. The sera of the ten patients reacted strongly to a beef extract, but not to pork and chicken extracts by both ELISA and immunoblotting. The sera of the five control subjects did not react to any of these meat extracts. Three bands having molecular masses of ~200 kDa, ~67 kDa and ~60 kDa were observed by immunoblotting after SDS-PAGE. Two fractions of the beef extract from a Sephadex-gel (G-200) filtration column strongly reacted with the sera of the beef-allergic patients by ELISA and immunoblotting: one fraction had the ~67 kDa component and the other had the ~200 kDa and ~60 kDa components. One of them (~67 kDa) was confirmed to be bovine serum albumin (BSA) by an analysis of the N-terminal amino acid sequence. We could not identify the others by sequencing, but the ~200 kDa and ~60 kDa components were presumed to be glycoproteins. Bovine gamma globulin (BGG: M.W. ~160 kDa) is a glycoprotein and has several subunits. The beef-allergic patients showed strong reactivity to the ~200 kDa and ~60 kDa components of pure BGG by immunoblotting. Inhibition-ELISA showed that pure BGG preparations strongly inhibited the binding of sera from the beef-allergic patients to the beef extract. These results suggest that the ~200 kDa, ~67 kDa and ~60 kDa components in the beef extract had strong allergenicity: ~67 kDa was BSA, and ~200 kDa and ~60 kDa were presumably aggregated BGG and it’s heavy chain, respectively.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology