Adult FPIES

Prevalence of FPIES in Adults

It has been anecdotally reported that FPIES can occur in adults, but only one confirmed case¹ has been published up to now and there is no epidemiological data available.

Symptoms
Acute FPIES typically presents with gastrointestinal symptoms with or without hypotension as seen in children.²Onset of symptoms after intake of the causative food is usually delayed. The case by Fernandes et al.¹ describes symptoms of vomiting, profuse blood-stained diarrhea, pallor and hypotension. This occurred about 95 minutes after last dose of oral challenge with scallops. The onset of symptoms in this case was much earlier than suggested by the patient’s history (i.e., two to four hours). In children, it usually occurs 0.5-6 hours after intake.²It is unknown if chronic FPIES can occur in adults.

Diagnosis
The gold standard to diagnose this condition is by means of oral food challenge (OFC).³ However, because of the risks associated with doing OFCs in these patients it is not usually done. NIAID Food Allergy Guidelines state that if patients (infants and children) report multiple reactions to the suspect food, a diagnosis may be based on a convincing history and absence of symptoms when the causative food is eliminated from the diet.^{3, 4} No particular guidance is given on adult FPIES or the food challenge dosages required to diagnose this condition in adults. OFCs can be considered if patients are keen to obtain a definitive diagnosis, if they have had only a single reaction, when presentation is atypical, or when other diagnosis is more likely gastroenteritis or scombroid poisoning.

Diagnosis relies on finding typical clinical features during the acute stage supported by certain laboratory markers as seen in children. The case by Fernandes et al.¹ found neutrophilic leukocytosis about one hour after onset of symptoms during food challenge (in children it has been found to peak at six hours). Other findings that may be found are thrombocytosis, metabolic acidosis, methemoglobinemia, stool leukocytes and eosinophils.²Skin prick test and specific IgE to implicated food are typically negative and serum tryptase levels are within normal limits.²

Pathophysiology
The pathophysiology of FPIES remains poorly understood. It is often considered to be a T-cell-mediated disorder. It is hypothesized that T-cell activation by food allergens may mediate local intestinal inflammation through an increase in TNF- α , and decreased expression of TGF-β receptors in the intestinal mucosa. This causes an increase in peripheral neutrophils seen in this condition. Eosinophils are increased in the GI tract but this is not specific.⁵

Th2 activation may be involved in pathophysiology of FPIES with an increase in Interleukin (IL)-4 and decrease in interferon-γ found after positive challenges, and increase in IL-10 after negative challenges. ^{5, 6}

The humoral responses noted are an elevated allergen-specific IgA and decrease in allergen-specific IgG4. Systemic specific IgE antibody responses are typically absent in FPIES but local food IgE in the gut mucosa has been postulated as a possible mechanism.⁵

Foods Involved
In contrast to foods mostly implicated in FPIES in infants and young children (such as milk, soy, rice and other grains, meat and poultry, eggs, and certain fruit and vegetables), FPIES in older children and adults are often related to seafood.⁷ Fernandes et al.¹ reported about an adult with reaction to scallops who also reacted to clams in the past, which is likely due to cross-reactivity seen among mollusks. This suggests that patients can react to other foods in the same family. A recent retrospective study by Tan and Smith⁸ found 31 adults in their clinic practice with symptoms suggestive of possible FPIES or non-IgE mediated food allergy, although they were not confirmed by food challenges. Most of the reactions were due to seafood (mollusks, crustaceans and fish) and egg but other foods like peanut, almond, mushroom, corn, chicken and duck were also implicated.

Clinical Dilemmas
Many allergists report that symptoms suggestive of FPIES are on occasion reported by adult patients, and mainly refer to ingestion of seafood. However, a sound diagnosis is rarely made as patients decline food challenges due to the severity of the reactions, even years after the incident. As many adults do not find it too cumbersome to avoid seafood or the particular seafood from their diet, they do not see the need for a more reliable diagnosis. FPIES is also frequently misdiagnosed as gastroenteritis, scombroid poisoning or food intolerance.

In Summary
FPIES is a rare and potentially severe food allergy that is frequently misdiagnosed. A high index of suspicion is required to make this diagnosis. Further studies looking at FPIES in adults are needed to better describe this phenomenon, focusing on new onset FPIES in adults, on unresolved (but often misdiagnosed) FPIES since childhood, foods implicated in adult FPIES, and OFC protocols in adults.

References

1. Fernandes BN, Boyle RJ, Gore C, Simpson A, Custovic A. Food protein-induced enterocolitis syndrome can occur in adults. J Allergy Clin Immunol; 130:1199-200.
2. Mane SK, Bahna SL. Clinical manifestations of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol; 14:217-21.
3. Feuille E, Nowak-Wegrzyn A. Definition, etiology, and diagnosis of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol; 14:222-8.
4. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol; 126:S1-58.
5. Caubet JC, Nowak-Wegrzyn A. Current understanding of the immune mechanisms of food protein-induced enterocolitis syndrome. Expert Rev Clin Immunol; 7:317-27.
6. Leonard SA, Nowak-Wegrzyn A. Clinical diagnosis and management of food protein-induced enterocolitis syndrome. Curr Opin Pediatr; 24:739-45.
7. Venter C, Groetch M. Nutritional management of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol; 14:255-62.
8. Tan JA, Smith WB. Non-IgE-mediated gastrointestinal food hypersensitivity syndrome in adults. J Allergy Clin Immunol Pract; 2:355-7 e1.

Provided by the I-FPIES Medical Advisory Board