Q:

10/9/2013
I have a 6 month-old pt with symptoms consistent with FPIES from avocado ingestion. With his 3rd and 4th exposure to avocado, he developed profuse emesis for 90 minutes, coupled with lethargy and hypothermia; all occurring 3 hours after exposure. He has been exclusively breastfed up until this point, with 7-8 exposures to banana, and 2-3 exposures to apple, peas, and squash without reaction. He has a history of a delayed eczematous rash to rice cereal after 3 days so this was stopped.

If IgE mediated food allergies can be ruled out, what is your recommendation in moving forward with further food introduction? Since we have the knowledge that 80% of patients with FPIES to a solid food will react to more than one food, should grains, legumes, poultry, dairy and soy be avoided as a cautionary measure, or should I be aware of other cross reactivities from avocado (other than known latex triggers ie banana, kiwi)? And if so, how long should these foods be delayed? Because this patient’s trigger for FPIES is unusual, I would most appreciate a little guidance.

A:

Thank you for your inquiry.

I can appreciate your need for advice in this regard because evidently FPIES due to avocado is extremely rare. I could not find a previous case reported in the medical literature.

Fortunately, there was a recent, comprehensive, and very helpful review of FPIES by Drs. Kirsi Jarvinen and Anna Nowak-Wegrzyn that was published in "In Practice." They deal in detail with the issue of long-term management which includes how long avoidance should be followed, breastfeeding, when and how to introduce new foods, when to consider reintroduction of the trigger food, and nutritional management. In addition, Table E5 of this article summarizes suggestions on when and how to introduce new foods.

In the same issue of this journal you will find another helpful article entitled "Food Protein-Induced Enterocolitis Syndrome: Insights from a Review of a Large Referral Population" by Ruffner, et al.

Copied below, for your convenience, are the sections from the Jarvinen/Nowak-Wegrzyn article that are pertinent to your inquiry, and there is also a link to the Table E5 mentioned above.

I think that the comments from this article will be very helpful to you, but nonetheless, I am also asking Dr. Anna Nowak-Wegrzyn, the coauthor of this excellent review and an internationally recognized authority in food allergy, to add any additional comments that might pertain to your particular case, especially regarding the observation that there is a large cross-reactive profile for IgE-mediated events between avocado and other foods. As soon as we hear from Dr. Nowak-Wegrzyn, we will forward her response to you. In the meantime, I am sending you this information.

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

The Journal of Allergy and Clinical Immunology: In Practice
Volume 1, Issue 4 , Pages 317-322.e4, July 2013
Kirsi M. Järvinen, MD, .Anna Nowak-Wêgrzyn, Food Protein-Induced Enterocolitis Syndrome (FPIES): Current Management Strategies and Review of the Literature

"Long-term management Management should be individualized, considering the reaction history and severity, specific IgE results, age of the child, and number and type of foods involved.

Strict allergen avoidance
Management consists of strict avoidance of the trigger food. Although patients with FPIES react to larger food amount (82% to >30-50 mL5), it is difficult to assess the patient's threshold dose because of delayed onset. Because of this and the fact that threshold dose may get smaller with repeated episodes, it is important to strictly avoid trigger food.18 Extensively hydrolyzed casein formulas are recommended instead of soy-based formula because of the possibility of concomitant CM and soy FPIES. If soy-based formula is chosen, a soy OFC is recommended. Amino acid formula is needed in approximately 10% to 15% of the infants. In severe cases, temporary bowel rest and intravenous fluids may be necessary. Ingestion of cooked forms of foods is not recommended, based on the presumed T-cell involvement, because high temperature does not destroy sequential allergenic epitopes recognized by T cells. However, in one report, patients with CM FPIES tolerated cooked forms of milk.35 More studies are needed to determine whether cooked foods could be tolerated by patients with FPIES.

Breast-feeding
Exclusive breast-feeding appears to protect against FPIES. Until recently, FPIES was reported only in formula-fed infants. Two reports were published of FPIES after ingesting breast milk because of a maternal intake of CM intake and soy.6, 7 However, among an additional 21 breast-fed infants with acute FPIES, only 3 mothers removed the trigger food from their diet; no FPIES episodes were reported in the 18 infants. IgE-mediated urticaria and anaphylaxis to foods ingested by breast-feeding mothers have been reported in infants.36, 37 Because FPIES is less common, reactions during exclusive breast-feeding might have been underreported. Small amounts of protein transferred to breast milk may be insufficient to meet the threshold dose, which is higher for FPIES than for IgE-mediated allergy.38 The amounts passed to breast milk vary significantly among mothers36; the protein is partially digested and processed. For these reasons, the causative food should only be removed from the maternal diet if reactions after breast-feeding occur or if the infant is failing to thrive.

Introduction of new foods
No controlled studies are available on food introduction in FPIES, and these recommendations are empirical, based on limited, existing data and our own experience (see Table E5 in this article's Online Repository at www.jaci-inpractice.org). Any food already tolerated by an infant should not be restricted. Yellow fruits and vegetables instead of cereal at 6 months of age have been suggested. If tolerated, grains, legumes, and poultry can be introduced to the diet.

Because of a high rate of multiple foods in solid foods FPIES, it may therefore be beneficial to avoid grains, legumes, and poultry in the first year of life because of the high likelihood of reacting to multiple foods.10, 20 Introduction of CM and soy in these infants may be attempted after 1 year of age, preferably under physician supervision, if there is no prior history of reactivity to these foods. Tolerance to one food from each high-risk group, for example, soy for legumes, chicken for poultry, or oat for grains, increases the likelihood of tolerance to other foods from the same group.20

Re-introduction of trigger food
The culprit food should be considered for reintroduction to the diet 12 to 18 months after the last reaction, in a physician-supervised setting.

Nutritional management
Considering the potential severity of the acute episodes as well as strict avoidance requirement, nutritional counseling should be offered to most patients with FPIES. Infants with multiple food FPIES are particularly vulnerable to nutritional deficits and feeding difficulties (Box 1, Case 3). Breast-fed young infants with reactions to first solid foods introduced to their diet may develop feeding difficulties. Food refusal may be related to past unpleasant experiences with solid food and can be magnified by parental apprehension. Counseling parents about strategies for enhancing feeding and oral skills is critical in these infants.

Natural History
Resolution of FPIES varies widely among reports from different countries, which may depend on the nature of the population studied (general vs referral) and the frequency of coexisting atopic diseases.5, 10, 23, 29, 33 Table E3 summarizes the studies on the natural history for different foods (see Table E6 in this article's Online Repository at www.jaci-inpractice.org). For CM and soy, reports from Korea and Israel show overall more favorable prognosis compared with the US studies.5, 10, 23, 33

Most children with FPIES have negative SPTs and undetectable serum food-specific IgE at diagnosis. Sicherer et al23 observed that children with detectable food-specific IgE tend to have a more protracted course and are at risk of developing IgE-mediated immediate-type symptoms, which was recently also reported by Onesimo et al.39 Therefore, including SPTs and/or measurement of serum food-specific IgE levels in the initial as well as follow-up evaluations is prudent to determine timing and the type of OFCs.

TABLE E5

Sincerely,
Phil Lieberman, M.D.

We have received Dr. Nowak-Wegrzyn's response. Thank you again for your inquiry.

Warm regards,
Phil Lieberman, M.D.

Response from Dr. Anna Nowak-Wegrzyn:
Thank you for your important clinical questions. There are very little data published to answer your question and I have to share with you our empiric approach.

1. If IgE mediated food allergies can be ruled out, what is your recommendation in moving forward with further food introduction?

A: We would continue feeding banana, apple, peas, squash and add other related fruit and vegetables, eg pear, peach, green beans.

2. Since we have the knowledge that 80% of patients with FPIES to a solid food will react to more than one food, should grains, legumes, poultry, dairy and soy be avoided as a cautionary measure, or should I be aware of other cross reactivities from avocado (other than known latex triggers ie banana, kiwi)?

A: There are no reports of cross-reacivity between avocado and banana or kiwi in FPIES that I am aware of and we have not seen that in our practice. I have been starting grains from quinoa, tapioca/arrowroot, and if well tolerated, followed by other grains. In general, if a child has FPIES to 1 non-grain solid, I would not necessarily delay intro of rice, oat and wheat past 1 st year.

3. And if so, how long should these foods be delayed?

A: I would usually delay introduction of milk and soy until 1 year of age. After 1 year, we would consider a supervised challenge in a child with multiple food FPIES. In a child who has tolerated various foods from different food groups, I would feel more confident and would consider a home introduction. Usually starting from loading maternal diet with dairy if still breast-fed, followed by milk in baked products, then cheese, yogurt and liquid milk, same for soy. We would look for soft signs, such as diarrhea, gas, discomfort during baked milk introduction more so than full blown acute fpies with severe emesis.

I hope this is helpful.

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