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Food protein induced enterocolitis and carrageenan intolerance

Question:

6/17/2019
I have a 7 month-old patient with h/o of FPIES to oat and +/- sweet potato. Patient came to me with already drawn IgE levels for foods by primary physician. Due to milk IgE at 4ku/L and severe eczema, child was switched from strictly nursing to Alimentum (powder) plus some nursing. He had been tolerating Alimentum (powder form). Recently child tried Alimentum Ready to Feed and developed repetitive projectile vomiting (responded to Zofran in ED). We are wondering if this was FPIEs and whether Carrageennan (the only difference between the two types of Alimentum) could be a possible trigger for FPIEs. I researched but did not see reports about Carrageennan and FPIES link. I was wondering if you have heard of this kind of case and what other foods related to carrageennan this patient should avoid.

Answer:

I shared your question with Dr. Anna Nowak-Wegrzyn, professor of pediatrics at the Jaffe Food Allergy Institute of the Icahn School of Medicine in New York. Her response is below.

“Thank you for sharing this interesting case. The reaction seems consistent with acute food protein-induced enterocolitis syndrome (FPIES). 1While the majority of FPIES reactions occur with larger doses of food, eg 1 oz of cow’s milk2, rare cases attributed to trace amounts of food have been reported. 3 Two cases of acute FPIES attributed to the probiotic yeast, Saccharomyces boulardii, have been described. I am aware of a case induced by locust bean [unpublished]. Considering that FPIES has been reported in association with variety of foods, including cereal grains, multiple fruits, starchy vegetables, meats, seafood, nuts and seeds; it is therefore possible that carrageenan might be an FPIES trigger.

Carrageenan is extracted from red seaweed (Irish moss, Chondrus crispus). It is a food additive, widely used in the food industry as a thickener, stabilizer and a gelling agent. It is an ingredient in chocolate milk, ricotta cheese, ice cream, condensed milk and infant formula. 4In laboratory animals (rats, mice), carrageenan has been used to induce anaphylactoid (non-immunologic anaphylaxis) reactions and to study mediators of inflammation. Carrageenan is a high-molecular-weight polysaccharide consisting of repeating galactose units and 3,6 anhydrogalactose (3,6-AG), sulfated and nonsulfated. The units are joined by alternating α-1,3 and β-1,4 glycosidic linkages and contain alpha-gal epitope, making carrageenan a potential cross-reactive allergen for people with alpha-gal allergy. Carrageenan has been identified as a trigger for anaphylaxis. 5”

In summary, it is very possible that your hypothesis that carrageenan could be the cause of the intestinal symptoms is correct. You should make the parents aware of other food sources of carrageenan as mentioned above. Since the mechanism for FPIES is not IgE dependent, I would not recommend testing for alpha-gal (galactose-alpha-1,3-galactose) specific-IgE. FPIES resolves spontaneously and hopefully you could try oat, sweet potatoe and carrageenan after avoidance of more than 1 to multiple years (6-8), although specific-IgE to the food, in the case of milk, and solid foods may have a longer time to resolution (9). Challenges for FPIES are associated with risk and sufficient support resource should be available to treat hypotension from a severe reaction.

1. Nowak-Wegrzyn A, Chehade M, Groetch ME, et al. International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology. The Journal of allergy and clinical immunology 2017;139:1111-26 e4.
2. Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. The Journal of allergy and clinical immunology 2011;127:647-53.
3. Mane SK, Hollister ME, Bahna SL. Food protein-induced enterocolitis syndrome to trivial oral mucosal contact. European journal of pediatrics 2013.
4. Tobacman JK. The common food additive carrageenan and the alpha-gal epitope. The Journal of allergy and clinical immunology 2015;136:1708-9.
5. Tarlo SM, Dolovich J, Listgarten C. Anaphylaxis to carrageenan: a pseudo-latex allergy. The Journal of allergy and clinical immunology 1995;95:933-6.
6. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M, J Allergy Clin Immunol. 2011;127(3):647.
7. Clinical features of food protein-induced enterocolitis syndrome. Sicherer SH, Eigenmann PA, Sampson HA J Pediatr. 1998;133(2):214.
8. Food protein-induced enterocolitis syndrome caused by solid food proteins. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH, Pediatrics. 2003;111(4 Pt 1):829.
9. Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience. Caubet JC, Ford LS, Sickles L, Järvinen KM, Sicherer SH, Sampson HA, Nowak-Węgrzyn A, J Allergy Clin Immunol. 2014 Aug;134(2):382-9. Epub 2014 May 28.

I hope this information is of help to you and your practice.

Anna Nowak-Wegrzyn MD, PhD, FAAAAI
Dennis K. Ledford, MD, FAAAAI