FPIES is a heterogeneous, non-IgE-mediated gastrointestinal food hypersensitivity that has been anecdotally reported in adults for many years, but only recently have there been case series published in the peer-reviewed literature describing this clinical entity in adult patients (5–8, 10). We hope our case series will better characterize and advance our understanding of this disease entity in adults. In our study, a Canadian cohort of 19 adolescent and adult patients presented with recurrent gastrointestinal symptoms after ingestion of a crustacean. The interval between ingestion of the implicated food and the onset of symptoms (mean of 2.8 hours) and reproducible symptoms to the food (4.8 reactions on average) is typical for a non-IgE mediated reaction. None of our patients had extra-gastrointestinal manifestations that later progressed to anaphylactic reactions.
We know from the literature that up to 25 percent of children and infants fulfilling the diagnostic criteria for FPIES have or develop IgE antibodies to the trigger food, possibly due to avoidance or pre-existing food allergy (4, 11). One of our patients was skin-prick test positive to shrimp. Clinically, her reaction was consistent with a non-IgE reaction given her gastrointestinal predominant symptoms and the time course of her reaction. As such, having a positive skin prick test does not preclude the diagnosis of FPIES and we chose to include her in the cohort.
There are some key differences in the clinical features of FPIES in adults when compared to children. We noticed a predominance of female patients (68.4%) with adult FPIES, as opposed to a male predominance of 50%-60% observed in children (4). This is consistent with Du et al and Gonzalez-Delgado et al who observed a 90% and 88% female predominance in their cohorts of adult FPIES patients respectively (5, 8). This may suggest a hormonal role in the pathogenesis of FPIES. Our findings of shrimp as the predominate food trigger for adult FPIES is consistent with previous cases studies in adult patients (5, 8). This is in contrast to cow’s milk and soy as the most common food trigger in FPIES in children (4). We did not find a strong correlation between a history of atopy and FPIES in adults (3 out of 19 patients), which is something often noted in children. This contrasts with Gonzalez-Delgado et al who noted 72% of their adult and adolescent patients with FPIES had an atopic background (8). Our cohort reported a large range of time to onset of symptoms after ingestion of food (range of 3 minutes to 6.5 hours), instead of the typical 1 to 4 hours suggested for pediatric FPIES. This may suggest that the time course of adult FPIES is less predictable than pediatric FPIES and may occur more rapidly (9). In children, solid food triggers for FPIES tend to vary based on geographic location as noted in previous studies involving children in Australia and Spain (12, 13). Interestingly, despite differences in geographic location in our Canadian cohort of patients, we saw predominately crustaceans as the implicated food in adult FPIES. This was similar to the findings of Gonzalez-Delgado et al, who conducted their study in Spain (8). Given the differences between adult FPIES and classical FPIES in the pediatric population, specific guidelines should be developed for diagnosis and management of FPIES in adults.
Little is known concerning the pathogenesis of FPIES. It is hypothesized that the ingestion of food allergens causes a T-cell mediated response that results in local inflammation leading to increased intestinal permeability and fluid shift (14). There may also be a role for transforming growth factor beta (TGF-β) receptors, activated peripheral blood monocular cells, and increased tumor necrosis factor (TNF-α) alpha in the intestinal mucosa involved in intestinal inflammation (15). Ondansetron has been shown to be beneficial in the treatment of FPIES in children, though the mechanism is unclear (16). To date, there have not been studies on its use in adult patients with FPIES; further research should be conducted to determine if it is effective in adults as well.
Adult FPIES is a newly recognized disease entity and the natural history of this condition is not well known. As such, there is often a significant delay in the time of symptom onset to diagnosis. We noted a prolonged delay in diagnosis with a median of 10 years from symptom onset to diagnosis, comparable to a median of 8 years noted by Gonzalez-Delgado et al (8). To aid in decreasing the delay in diagnosis of FPIES in adults, it is important to educate other medical specialties including gastroenterology, emergency medicine, and family medicine concerning this disease entity. It is also important to increase awareness of FPIES in adult patients, given the possibility of a severe reaction which may result in serious dehydration and volume depletion.
Limitations to our study include potential recall bias given its retrospective nature, as well as lack of confirmatory testing. Not all patients had serum specific IgE-testing or serum tryptase drawn at time of reaction. Not all patients had oral food challenges completed as many were not willing to undergo the challenge and preferred strict avoidance of the implicated food.