Non-IgE-mediated Food Sensitivities in Children

Educational Objectives

The goal of this program is to improve non-immunoglobin (Ig) E-mediated food sensitivities in children. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate among signs and symptoms of various food protein-induced allergic conditions in infants.
2. Identify symptoms associated with eosinophilic esophagitis.

Summary

Food protein-induced (FPI) allergic proctocolitis (FPIAP): presents with streaks of bright red blood in stools, often with excess mucus; may account for ≈60% of rectal bleeding in healthy infants and usually appears in the first few months of life (6–12 mo); seen in breast- and bottle-fed babies; earlier presentation in premature babies may be related to change in intestinal flora because of their stay in neonatal intensive care unit; common triggers — most common trigger is cow's milk; other foods include eggs, soy; >1 food is uncommon (can be treated by limiting that food); multiple food allergy usually includes allergies to milk and another food item and is more likely in children with atopic dermatitis (AD); symptoms — children appear clinically well but may be fussy; poor weight gain and food refusal are rare; in severe cases (rare), considerate blood loss can lead to iron deficiency anemia and eosinophilia; diagnosis — based on clinical symptoms, with other common causes of blood in the stool ruled out; biopsy is not necessary but could show mild colitis; allergy test is usually not indicated and should be negative; a small percentage of children might develop IgE-mediated allergies to food, which is seen commonly with AD and systemic symptoms, eg, vomiting (should not occur in pure FPIAP), and may be related to delaying introduction of milk into diet

Treatment: usually avoidance; bleeding resolves in a few days and can last for weeks in some patients; mucous in stools takes longer to resolve; avoid milk and soy — ≤30% of children with milk allergy also have soy allergy; breastfeeding mothers should avoid these foods as well; severe cases necessitate switching to extensively hydrolyzed formula; if there is no response to milk and soy, eggs should be removed to check for allergy; 5% to 10% of breastfed babies do not improve despite maternal avoidance to suspect foods; however, bleeding disappears immediately when these infants are put on a nonmilk formula diet; change to elemental formula and allow small amounts of blood in the stool as it eventually resolves; natural history — food reintroduction can be done at age 1 yr; in 2% to 3% of patients, the allergy does not resolve until 2 or 3 yr of age; if blood returns, the food needs to be stopped and reintroduced after few months

Differential: anal fissure is most common, followed by swallowed maternal blood (newborns), Meckel, polyp, or viral infection; children with necrotizing enterocolitis and very early onset inflammatory bowel disease are much more ill-appearing

Types of infant formula: most people use intact cow's milk formula or intact soy protein-based formula; partially hydrolyzed milk formula is not suitable for milk-allergic patients (MAPs), but extensively hydrolyzed milk formula is appropriate; elemental diet of free amino acids is suitable for MAPs

FPI enterocolitis syndrome (FPIES): hallmark is delayed onset of emesis, starting 1 to 3 hr after eating; acute — acute episodes involving intermittent exposure to food cause reproducible emesis with food (may lead to hypothermia, dehydration, acidosis, and possible later-onset diarrhea); may have neutrophilia, thrombocytosis, hypoalbuminemia; chronic — occurs with regular exposure to food; involves intermittent emesis, chronic diarrhea, failure to thrive, lethargy, poor weight gain, food aversion; usually seen in younger children; very rare in breastfed children; usual onset is several days after initiation of formula diet; symptoms improve when formula is stopped; reintroduction leads to chronic episode of FPIES; onset — usually starts within first 6 mo of life, possibly earlier with milk allergy, ie, not breastfed; occurs in breastfed babies during transition to formula; solid foods trigger reaction at age 4 to 6 mo; 80% of cases are girls; most common allergen is seafood; diagnosis — allergy tests are negative; a relatively high percentage of children develop IgE allergy over time; major criteria include vomiting a few hours after ingestion in the absence of other IgE-mediated symptoms, eg, swelling, rash, coughing; minor criteria are >1 occurrence, vomiting with different foods, vomiting necessitating resuscitation in emergency department; oral food challenge is not needed for diagnosis but can be done, however, there can be severe risk of vomiting; consider if patient history is clear

Treatment: avoidance; milk, soy, and grains (rice, oats) cause FPIES and should be eliminated; other reported foods include eggs, fruits, vegetables, seafood; multiple food allergy not uncommon; symptoms of acute cases usually resolve within a few hours of stopping food; it takes several days for symptoms of chronic FPIES to resolve; triggers vary among studies and countries; solid-food-induced FPIES increase incidence of reaction to other solids (introduce new solid foods carefully); bananas, avocados, and sweet potatoes are associated with risk of inducing FPIES; most cases self-resolve but can take a few years; challenge patients in office 1 to 2 yr after last reaction and give intravenous fluids while introducing food to check for sustenance of FPIES; acute episodes — rehydration and administration of ondansetron; no evidence for efficacy of steroids, antihistamines, and epinephrine as these are not immune cell-mediated

Food aversion: very difficult to treat; especially prevalent in cases of multiple food allergies and severe symptoms; multidisciplinary approach involving dietician, occupational therapist, and psychologist for counseling patient and family is important

FPI enteropathy: presents with chronic diarrhea; usually there is no blood in stool but has fat because of malabsorption; early satiety and failure to thrive are common; usually presents in older children (6 mo to 2 yr of age); onset of symptoms is insidious; diagnosis — laboratory tests are used for finding levels but not diagnosing; biopsy can be done (reveals celiac-like finding with villus atrophy but none of the extra-intestinal symptoms of celiac disease); treatment — includes empirical elimination of food; symptoms resolve at 1 to 2 wk after elimination, but villous injury may take months to recover; rechallenge can be done at home 1 to 2 yr after the last reaction triggered by food

Eosinophilic esophagitis (EoE): very common; associated with several symptoms but often missed because of nonspecificity; symptoms vary with age; infants and toddlers have feeding difficulty, food refusal, vomiting, and abdominal pain; older children have upper gastrointestinal symptoms, reflux-like symptoms often resistant to therapy, occasional choking or gagging with meals, and regurgitation; adolescents and adults have classic symptoms, eg, dysphagia, impaction, subtle unconscious change in eating behavior, avoidance of dry or hard food, taking small bites, and cutting foods into small pieces, followed by drinking; diagnosis — EoE is a clinicopathologic disease (suspected clinically and confirmed by biopsy); >15 eosinophils per high power field confirms a suspected diagnosis; familial tendency — has male predominance and runs in families; sibling risk ratio (λs) is 80 (that for asthma is only 2); natural course — does not remit or lead to malignancy but can cause strictures and might require dilations over time

Treatment: clinical and histological response; some patients improve with proton pump inhibitors only; topical steroid is hallmark of treatment; swallowed steroids involves swallowing fluticasone inhaler puffs; budesonide can also be used (high response rates); allergy tests are not helpful; empiric food elimination diet can be followed; management involves cycle biopsy and dietary changes to be repeated until symptoms resolve; dupilumab is a promising candidate for therapy; sticking of swallowed coins in children could be associated with EoE, especially with food impaction, dysphagia, and atopy

Readings

Leonard SA, Pecora V, Fiocchi AG, et al. Food protein-induced enterocolitis syndrome: a review of the new guidelines. World Allergy Organ J. 2018 Feb 7; 11(1):4. doi: 10.1186/s40413-017-0182-z; Mennini M, Fiocchi AG, Cafarotti A, et al. Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol. World Allergy Organ J. 2020 Oct 1; 13(10):100471. doi: 10.1016/j.waojou.2020.100471; Muir A, Falk GW. Eosinophilic esophagitis: a review. JAMA. 2021 Oct 5; 326(13):1310-1318. doi: 10.1001/jama.2021.14920; Nowak-Węgrzyn A. Food protein-induced enterocolitis syndrome and allergic proctocolitis. Allergy Asthma Proc. 2015 May-Jun; 36(3):172-84. doi: 10.2500/aap.2015.36.3811.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Ferdman was recorded at Pediatrics in the Islands: Clinical Pearls 2022, held on June 25 to July 1, 2022, and presented by The American Academy of Pediatrics, California Chapter 2; and Children's Hospital Los Angeles Medical Group. For information on future CME activities from this presenter, please visit https://www.chla.org/cme-conferences. Audio Digest thanks Dr. Ferdman and The American Academy of Pediatrics, California Chapter 2; and Children's Hospital Los Angeles Medical Group for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

PD684002

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.