Q:

6/2/2013
The patient is a 38-year-old female who presents with a 2 to three-month history of recurrent vomiting after egg exposure. The symptoms occur within 20-30 min. and may last for several hours. There were no other symptoms/signs. She tolerates chicken without any difficulty and she has no upper and/or lower respiratory tract symptoms with bird exposure. She seems to react only to pure egg products. She seems to tolerate egg in baked products. Skin tests show a wheal of 3 mm and a flare of 10 mm to whole egg and a wheal of 3 mm with a flare of 5 mm to parakeet. Her presentation seems to be consistent with adult onset FPIES to egg but the vomiting seems to come on too quickly. At this time she is avoiding pure egg products and she has an FPIES letter should she go to the emergency room. Do you have any other thoughts in regards to her management? Does she need auto injectable epinephrine? Would testing for serum egg and/or bird allergens be useful? Could this possibly be an early case of bird-egg syndrome? Thank you very much for answering this question.

A:

Thank you for your inquiry.

At this point in time, in my opinion, it is not possible to make a definitive diagnosis in your patient, but I would favor bird-egg syndrome over FPIES. If for no other reason, FPIES is rare in adults (see previous inquiry and response by Dr. Anna Nowak-Wegrzyn copied below). It has been reported in adults, but to my knowledge, in only a handful, at most, of instances, and only to shellfish (1). So, if only from a statistical standpoint, bird-egg syndrome would be the more likely of the two. In addition, you did demonstrate a positive skin test to both egg and parakeet. This also suggests bird-egg syndrome as a possibility.

Bird-egg syndrome is more likely to occur in adults, but has been reported in children as well. There seems to be a female predominance in the adult population. You tested your patient to parakeet, and I am assuming that she has a parakeet in the home. In most instances, it is felt that the sensitization occurs through inhaled bird allergen, and parakeets do produce significant amounts of small particle allergens capable of reaching the alveoli. Respiratory sensitivity to parakeets is well documented. In addition, the allergens of parakeet do demonstrate cross-reactivity with the allergens of chicken.

As opposed to typical egg allergy, where the responsible allergens are in the egg white, the allergen responsible for bird-egg syndrome (livetin) is found in the yolk, and is a component of chicken serum albumin (2, 3, 4). Patients with bird-egg syndrome therefore often show evidence of respiratory allergy, but gastrointestinal symptoms can also occur in the absence of respiratory manifestations. It is possible that your patient does have bird-egg syndrome. Also in keeping with this possibility is the fact that some patients (but not all) can eat egg in baked goods, also in keeping with the observation in your patient.

Having made these introductory remarks, I will try and answer your questions.
1. Do you have any other thoughts in regards to her management?

a. Regardless of the diagnosis, clearly your patient should avoid the ingestion of eggs.

b. If the diagnosis of bird-egg syndrome can be established, she should also avoid exposure to indoor birds. So, if she does have a parakeet, in this case, it would be best for her to remove it from the home.

c. A possible way to establish the diagnosis of bird-egg syndrome is discussed below.

2. Does she need auto injectable epinephrine?

It is certainly important for her to have an “FPIES letter” for presentation to an emergency room; however, one must be careful because epinephrine does not characteristically help patients with FPIES, and most experts do not recommend an epinephrine autoinjector for such patients. On the other hand, as you know, if this is bird-egg syndrome, an IgE-mediated reaction underlies the pathology, and epinephrine could be helpful. So, one must be careful not to exclude the possibility of epinephrine in your patient, and a diagnosis of FPIES would make its use unlikely. You might therefore consider “hedging your bets” until a diagnosis has been established. One way to do that would be to add a caveat in your letter stating at this time the diagnosis is not established, and although epinephrine is not characteristically used in FPIES, if anaphylactic manifestations occur, since your patient could have an IgE-mediated reaction, you have given her a prescription for an automatic epinephrine injector and epinephrine can be used at the discretion of the physician caring for her at the time.

3. Would testing for serum egg and/or bird allergens be useful?

Since there is no test for FPIES, testing that strongly suggests a diagnosis of bird-egg syndrome is the only way that you would be able to clarify which of the two entities is responsible. Therefore I would suggest further testing as follows:

a. I would consider prick-to-prick testing with raw egg yolk as well as egg white. If this was bird-egg syndrome, you characteristically would have a positive test to yolk and a negative test to egg white (unless unrelated sensitivity to egg white allergens was present).

b. There are a number of commercially available serum-specific IgE tests that might help clarify the diagnosis. These are:

i. nGald3, Conalbumin. Although this is a component of egg white, it can cross-react with antigens of chicken serum albumin
ii. Egg white
iii. Egg yolk
iv. Chicken
v. Parakeet (Budgerigar droppings)
vi. Budgerigar feathers
vii. Chicken serum proteins

If your patient does have bird-egg-syndrome, you would expect positive tests to at least a portion of these, especially chicken serum proteins and egg yolk.

Finally I have copied below a link to reference four. It would be very helpful to you and is available without charge.

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

References:

(1) Bryan N. Fernandes, Robert J. Boyle, Claudia Gore, Angela Simpson, Adnan Custovic et al. Food protein–induced enterocolitis syndrome can occur in adults. Short communication. Journal of Allergy and Clinical Immunology, November 2012; Vol. 130, Issue 5, Pages 1199-1200.
(2) The Journal of Allergy and Clinical Immunology. Volume 93, Issue 5 , Pages 932-942, May 1994.
(3) Allergol Immunopathol (Madr). 2003 May-Jun;31(3):161-5.
(4) Allergy. Volume 56, Issue 8, pages 754–762, August 2001.

Chicken serum albumin (Gal d 5) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome

Food protein-induced enterocolitis syndrome (FPIES) in adults
Previous inquiry and response:
Question:
I have 3 adults in my clinic who experience symptoms similar to FPIES. One has severe diarrhea, abdominal cramping within 3 hours of eating poultry. He required IV fluids on two occasions. One adult who developed abdominal cramping, diarrhea, fever to 103 6-8 hours after eating an omelet (Symptoms reproducible with eating omelet/scrambled eggs but tolerant of egg containing baked goods.) and one young woman with recurrent symptoms of abdominal pain, cramping and profuse diarrhea. Colonoscopy shows neutrophils and eosinophils. What is the best way to evaluate these patients? Is skin testing valuable? Patch testing to foods? Should they have epi pens?

Answer:
Thank you for your recent inquiry.

I have no personal experience dealing with FPIES in adults or children, and therefore am going to ask for an opinion from Dr. Anna Nowak-Wegrzyn, who fairly recently published an excellent review of this syndrome in Current Opinion in Allergy and Clinical Immunology, 2009, 9:371-377. As soon as I hear from Dr. Nowak-Wegrzyn, I will forward her response to you.

Thank you again for your inquiry.

Addendum:
Below is the response we received from Dr. Nowak-Wegrzyn. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Anna Nowak-Wegrzyn:

There are no published reports of adults with FPIES however I have heard of them anecdotally, mostly in the context of shellfish (particularly mollusk) ingestion. However, all those adults presented with profuse emesis within 2-3 hours of food ingestion. In children, I have never seen isolated diarrhea in the absence of preceding emesis or at least significant nausea and abdominal discomfort. As far as body temperature is concerned, in children, hypothermia has been reported, not fever. The first two patients are more likely to have some food-induced condition, perhaps FPIES, although their manifestations are far from “typical”. I would perform skin test and measure serum sIgE to poultry and egg, although they would most likely be negative. As far as patch testing is concerned, in our hands it has never been helpful, however, we usually perform patch testing prior to an oral food challenge following a prolonged period of food avoidance (about 18 months), which may affect the sensitivity of the patch test. If the patch test were positive, you might recommend food avoidance. If the patch test were negative, there is no guarantee that the patient will tolerate the food. The most definitive approach would be to perform the supervised oral challenge and to monitor symptoms, as well as body temperature, WBC, platelets, and blood stool. We do not prescribe epi pens for FPIES patients, however, once we establish FPIES diagnosis, we provide a letter explaining FPIES and outlining the treatment plan for acute reactions which emphasizes rapid intravenous hydration and a single dose of methylprednisolone. I might prescribe EpiPen if I found evidence of sIgE and there was h/o severe reactions with hypotension.

Regarding your third patient, it is difficult to assess her based on the limited information. It sounds like she has intermitted GI symptoms not related to any specific food ingestion. The results of colonoscopy are not typical for an allergic process, eosinophils are frequently seen in the colon. I would like to rule out IBD, celiac disease, as well as irritable bowel syndrome before delving into food allergy. The approach might be modified based on the additional atopic features and family history.

Kind regards,
Anna Nowak-Wegrzyn, M. D.
Associate Professor of Pediatrics
Jaffe Food Allergy Institute
Mount Sinai School of Medicine

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology