Version May 2024
INTRODUCTION — Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) mediated gastrointestinal food hypersensitivity that manifests as profuse, repetitive vomiting, sometimes with diarrhea, leading to dehydration and lethargy in the acute setting, or chronic, watery diarrhea with intermittent vomiting, leading to weight loss, failure to thrive, dehydration, and metabolic derangements in a chronic form [1-3]. This disease primarily affects infants. It is most commonly caused by cow's milk (CM) or soy protein, although other foods can be triggers [4,5].
A number of gastrointestinal disorders in children have been attributed to immunologic reactions to dietary proteins. Immunologic reactions to dietary proteins may be classified as IgE mediated, non-IgE mediated (T cell), or mixed (IgE and T cell mediated). The entire gastrointestinal tract can be affected, from the mouth to the rectum. Most of these disorders affect a specific region of the gastrointestinal tract, such as eosinophilic esophagitis (EoE), eosinophilic gastritis, food protein-induced enteropathy, enterocolitis, or proctocolitis. FPIES has some features that overlap with the other non-IgE-mediated gastrointestinal allergic disorders, food protein-induced enteropathy, and proctocolitis. (See "Clinical manifestations of food allergy: An overview" and "Food protein-induced allergic proctocolitis of infancy".)
The diagnosis is based upon the presence of consistent clinical features with improvement following withdrawal of the suspected causal protein. Affected children are often misdiagnosed as having acute viral gastrointestinal illness or sepsis, delaying diagnosis of FPIES for many months. An oral food challenge (OFC) is sometimes performed to confirm the diagnosis or to determine resolution of the food allergy. Treatment consists of elimination of the food trigger(s) from the diet, anticipatory guidance regarding complementary feeding, periodic reassessments for resolution, and managing acute emergencies [6].
EPIDEMIOLOGY — Non-IgE-mediated and mixed gastrointestinal immune reactions to cow's milk (CM) proteins are estimated to account for up to 40 percent of CM protein hypersensitivity in infants and young children [1,7]. FPIES represents the severe end of the spectrum of food protein-induced gastrointestinal diseases in infants and is far less common than proctocolitis [8,9]. The incidence ranges from 0.015 to 0.7 percent [10,11]. There is a slight male predilection (52 to 60 percent) in FPIES [10-13]. Reports of FPIES in siblings of an affected child are rare. (See "Food protein-induced allergic proctocolitis of infancy".)
In a large, Israeli, population-based birth cohort from a single hospital, 0.34 percent of infants (44 of 13,019) were diagnosed with FPIES (confirmed by resolution of typical FPIES symptoms with removal of CM from the diet and/or a clinician-supervised oral food challenge [OFC] to CM in the first year of life), suggesting that FPIES may be more common than previously appreciated [10]. The incidence of IgE-mediated cow's milk allergy (CMA) in this same cohort was 0.5 percent.
Another study used data from the Australian Pediatric Surveillance Unit that provides monthly reports from 1400 involved pediatricians and is estimated to represent at least 50 percent of all eligible pediatricians in Australia [11]. They provided the pediatricians with a standardized case definition of acute FPIES and collected monthly reports of new cases of acute FPIES in children younger than two years old. A total of 230 infants with FPIES were identified, giving an estimated annual incidence of 15.4 per 100,000. While this estimate dispels the myth of FPIES as a rare disorder, it is possible that it underestimates the true incidence of FPIES due to the methodologic limitations of the voluntary reporting system. This study did not address the incidence of chronic FPIES, although it is estimated that acute FPIES accounts for the majority of the FPIES cases.
In Spain, FPIES was reported to affect 0.7 percent of infants younger than 12 months in a single-center, unselected, population-based birth cohort (n = 1142) [14]. CM, hen's egg (HE) yolk, and fish (hake) were the most common triggers.
A population-based survey of food allergies in the United States was administered online or via telephone to a nationally representative sample of 53,575 households between 2015 and 2016 [15,16]. Lifetime, physician-diagnosed FPIES was estimated to affect 0.51 percent (95% CI 0.42-0.62) of the US population under the age of 18 years and 0.22 percent (95% CI 0.17-0.28) of adults (18+ years), with an overall prevalence of 0.28 percent (0.24-0.33 percent). In another study from the US, among 158,510 pediatric patients in a birth cohort, 214 patients met 2017 FPIES diagnostic criteria. Pediatric FPIES incidence was between 0.17 and 0.42 percent depending upon birth year. As in prior reports, most patients had an acute presentation (78 percent), and CM, soy, oat, rice, potato, and HE were common triggers. The mean age of diagnosis was 6.8 months [17].
PATHOGENESIS — FPIES is triggered by non-IgE-mediated food hypersensitivity. However, the exact underlying mechanisms of FPIES are not clearly understood. It is postulated that ingestion of food allergens causes local inflammation mediated by T cells, leading to increased intestinal permeability and fluid shift [18,19]. However, baseline intestinal absorption was normal in a group of infants with FPIES confirmed by oral food challenge (OFC) [20]. Activated peripheral blood mononuclear cells, increased tumor necrosis factor (TNF) alpha, and decreased expression of transforming growth factor (TGF) beta receptors in the intestinal mucosa may be involved in the intestinal inflammation [9].
Systemic food-specific IgE antibodies (determined by serum food-specific IgE and/or skin prick test) are not detected in the majority of patients with FPIES. However, up to 25 percent of children have evidence of specific IgE to the FPIES-inducing food [21-24]. Intestinal mucosal IgE may facilitate the antigen uptake and local intestinal inflammation [25], but this requires further study. A decrease in serum food-specific immunoglobulin G4 (IgG4) antibody and an increase in serum food-specific immunoglobulin A (IgA) levels were noted in one study [26]. A subsequent study found that both casein-specific IgG4 and IgA antibodies were significantly decreased in cow's milk (CM) FPIES [27].
Profiling of whole blood by mass cytometry demonstrated activation of cells of the innate immune system (monocytes, neutrophils, natural killer cells, and eosinophils) in addition to T lymphocytes after food challenge in children with FPIES [28]. This activation was not observed in children who had outgrown FPIES. Innate immune activation was confirmed by ribonucleic acid (RNA) sequencing in a larger cohort. Proteomic analysis of peripheral blood showed elevated interleukin (IL) 17a, IL-17c, and chemokine (C-C motif) ligand (CCL) 20, in addition to regenerating family member 1 alpha (REG1A), which regulates intestinal mucosal barrier downstream of IL-22. Cellular sources of IL-17 were identified as CD4+ T helper type 17 (Th17) cells; however, mass cytometry indicated preferential activation of nonconventional T cell populations, including gamma-delta T cells and CD3+CD4-CD8-CD161+ cells [29].
Untargeted serum metabolomics identified 34 metabolites that were significantly increased following a symptomatic food challenge, in particular, steroids in the corticosteroid and androgen (pregnenolone and progestin) families, inosine, and metabolite of serotonin (5-hydroxylindoleacetate) [30]. Adenosine, inosine, and urate are a part of the purine pathway initiated by adenosine triphosphate (ATP). Adenosine in the extracellular space binds P1 purinergic receptors that exert antiinflammatory effects through the generation of intracellular cyclic adenosine monophosphate (cAMP) and suppresses immune cell functions and proliferation in monocytes and T cells. Inosine was significantly and positively correlated with REG1A, a regulator of mucosal barrier function that was previously reported to be upregulated after an oral food challenge (OFC).
In a small study, plasma metabolic profiles were different among patients with cow's milk allergy (CMA), with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM FPIES compared with IgE-mediated CMA [31].
Food triggers — Although CM and soy protein have traditionally been reported as the most common triggers in young infants, more studies now indicate that solid foods, such as rice, oat, hen's egg (HE), and fish, are also triggers.
Milk and soy — The most common food triggers in FPIES are CM and soy (classic FPIES), with reactions occurring to infant formula during the first months of life. While several studies have shown that over 50 percent of infants with FPIES react to both foods [22,32], none of the 44 infants diagnosed with CM FPIES in a birth cohort study in Israel showed sensitivity to soy [10]. This difference could be attributed to a milder phenotype reported from a nonselected birth cohort compared with a more severe phenotype reported from allergy and gastroenterology referral populations. Alternatively, this could be attributed to different patterns of soy formula use in infancy. Globally, CM remains the single most common FPIES trigger [33].
CM FPIES in exclusively breastfed infants is rare, suggesting a protective role of breastfeeding that may be attributed to predigested and partially processed food allergens as well as presence of TGF-beta and IgA in mother's milk [13]. Only a few cases of exclusively breastfed infants with CM FPIES have been reported in the literature [34-36], and there are no reports in the literature of soy FPIES in exclusively breastfed infants.
FPIES to goat's milk was reported in an Italian series [37].
Solid foods — FPIES may be induced by solid food, including grains (rice, oats, barley, corn, wheat); meat and poultry (beef, chicken, turkey); HE (egg white and egg yolk); vegetables and fruit (white potato, sweet potato, squash, string beans, avocado, mushroom, banana, apple, tomato); legumes (peanut, green peas, lentils); tree nuts; seafood (fish, crustaceans, molluscs); seeds (sesame); and the probiotic Saccharomyces boulardii [8,12,13,18,21,37-50]. Among infants with solid-food FPIES in one series, 80 percent reacted to more than one food, 65 percent were previously diagnosed with CM and/or soy FPIES, and 35 percent were breastfed [13]. Infants with early-onset FPIES and reactions to fruits or vegetables are at higher risk for reacting to multiple food triggers [11].
Cereal grains — Rice and oat are the most common solid foods inducing FPIES [12]. In one case series, rice was responsible for 46 percent of FPIES episodes requiring hospitalization [51]. Children with rice-induced FPIES were more likely to have multiple food sensitivities and severe symptoms requiring intravenous fluid resuscitation compared with children with CM- or soy-induced FPIES.
Those with a history of FPIES to one grain have an approximately 40 to 50 percent chance of developing FPIES to other grains. However, wheat FPIES has not been reported in infants with oat or rice FPIES [7,13].
Egg — HE is among the common triggers of FPIES. The reported frequency of infantile HE FPIES is approximately 11 percent in Australia and the US and up to 36 percent in Turkey [24,52,53]. In an Italian multicenter study, among 61 children with HE FPIES, 47 (77 percent) tolerated cooked HE at the mean age 30.2 (range: 7 to 120) months; of them, 32 (68.1 percent) tolerated raw HE at a food challenge done at a mean age 43.9 (range: 18 to 120) months [54]. In Japan, a marked increase in HE FPIES incidence was observed over the five-year period from 2014 to 2019, coinciding with changes in infant feeding practices resulting in earlier introduction of HE into infants' diet [55].
Seafood — In Spain, Italy, and Greece, fish are the most common solid food triggers in infantile acute FPIES, likely reflecting the local dietary patterns. Fish FPIES in infants and young children has less favorable prognosis than other foods. In a single-center study in Spain, only 3 of 16 patients (18.7 percent) became tolerant by mean age 4.5 years [49].
In older children and adults, fish and shellfish are the most common triggers of FPIES. In adults with seafood FPIES, overall 60 percent react to a single food group. Fifty percent with fish FPIES react to a shellfish (crustacean or mollusk), 40 percent with crustacean FPIES react to a mollusk, and 55 percent with mollusk FPIES react to crustacean and/or fish [56].
Peanut — Peanut was an uncommon trigger for acute FPIES, generally representing less than 2 percent of cases in large series. However, more recent reports have highlighted the possibility of increasing incidence of infantile peanut FPIES [57,58]. One retrospective, single-center study identified 14 cases of peanut FPIES from 2017 to 2019 compared with no cases in the same institution between 2001 and 2011 [58]. Possible association with early introduction remains speculative in the absence of a comparison group without early introduction, requiring a prospective or case-control study. Pediatricians and allergy specialists should consider acute FPIES in the differential diagnosis of adverse reactions to peanut in infancy.
Multiple-food FPIES — The reported proportion of patients with single- versus multiple-food FPIES varies widely, between 40 to 80 percent depending upon the study population and methodology. In general, higher rates of multiple-food FPIES are reported from studies based upon the surveys among caregivers compared with studies based upon data from allergy practices. In a small subset of infants and children, three or more triggers were documented in 9 to 18 percent [23,59]. Compared with FPIES due to two or fewer triggers, patients with multiple triggers were more likely to develop food aversion (43.2 versus 16.9 percent) and to have poor weight gain (21.6 versus 6.6 percent). The patients with multiple triggers frequently reacted to HE, soy, grains (oat, rice, wheat, and barley), vegetable (sweet potato, legume), fruits (avocado, banana), and turkey but were less likely to have shellfish-related FPIES.
CLINICAL FEATURES — The clinical features of FPIES are summarized in the table (table 1) [10,12,23,37,60,61].
Age of onset — Symptoms of classic FPIES usually begin in early infancy, within one to four weeks following introduction of cow's milk (CM) or soy protein. In extreme cases, symptoms may begin within the first days of life. The first description of the disorder included nine infants who presented with severe vomiting and diarrhea, developing an average of 11 days after birth (range 4 to 27 days) [61]. In the Israeli birth cohort previously discussed, all 44 infants with CM FPIES presented with symptoms within the first six months of life [10]. Delayed introduction of CM or soy in breastfed infants may result in later onset.
The mean age at onset of solid-food FPIES tends to be later than that of CM and soy FPIES, typically presenting when these foods are first introduced between the ages of four to seven months [12,62]. The development of FPIES upon introduction of foods after one year of age is rare, although onset of a non-IgE-mediated gastrointestinal food hypersensitivity similar to FPIES, most commonly triggered by shellfish, fish, and/or hen's egg (HE), has been observed in older children and adults [23,62-64]. (See 'FPIES in adults' below.)
Chronic versus acute presentation — The disease typically presents in two phases [10,12,60,61,65]. The initial presentation of CM- or soy-induced FPIES in infancy is that of a chronic disease while the food antigen is ingested on a regular basis. This can be followed by an acute phase if the antigen is removed from the diet and subsequently reingested, with symptoms occurring approximately two hours after ingestion and lasting several hours. An acute presentation is also seen when the antigen is ingested intermittently. Young infants with FPIES due to CM- and/or soy-based formulas usually have a chronic presentation, whereas solid-food FPIES can have an acute or chronic presentation depending upon the frequency of ingestion of the offending food. In a retrospective review of 203 patients with FPIES, 180 had reported acute, 8 chronic, and 15 both acute and chronic FPIES. Oat (34.5 percent), rice (29.6 percent), and CM (19.2 percent) were the most common food triggers in acute FPIES, whereas, in chronic FPIES, 87 percent of cases were caused by CM and 21 percent by soy. The median age of onset of acute FPIES was older, 6.0 (interquartile range [IQR]: 5.0 to 7.0) months compared with the median age of onset of chronic FPIES of 0.4 (IQR: 0.0 to 1.7) months [59].
The following clinical vignette describes features of chronic and acute FPIES.
A full-term female infant who was initially exclusively breastfed was started on CM-based formula supplementation at four weeks of age. The baby developed frequent episodes of watery stools with occasional mucus, intermittent vomiting, and poor weight gain over a two-week period of daily formula intake (chronic FPIES).
The baby was then returned to exclusive breastfeeding until one feeding with a CM-based formula at 12 weeks of age. Approximately 90 minutes after that feeding, she developed repetitive vomiting and became lethargic (acute FPIES episode). A full sepsis work-up, toxicology, and metabolic screening were done in the emergency department (ED). She received intravenous fluid resuscitation and antibiotics and was observed in the hospital for three days. Blood-tinged diarrhea was noted only the first hospital day. She tolerated an extensively hydrolyzed casein formula and was discharged after three days when cultures were negative.
She avoided CM strictly and tolerated several solid foods introduced from five to seven months of age without symptoms, until an infant jar food containing cheese was given. Similar to the previous episode, she developed repetitive vomiting and lethargy 90 minutes after ingestion and required intravenous fluid resuscitation (acute FPIES episode).
Nearly all patients present with vomiting, which is projectile, repetitive in the acute presentation, and intermittent in the chronic setting, and are commonly pale and ill appearing [9,10,12,23,37,60,61]. Overall, approximately 75 percent of infants with FPIES appear seriously ill, and 15 percent develop hypotension and require hospitalization [9]. Other symptoms that can occur in both the chronic and acute presentations include diarrhea, abdominal distention, dehydration, pallor, and lethargy. In acute FPIES, repetitive emesis usually begins within 1 to 4 hours and diarrhea within 2 to 10 hours (mean onset 5 hours) of ingestion [61]. Patients with acute presentations tend to be sicker and may develop pallor, hypotonia, hypotension/shock, and/or hypothermia; however, these symptoms resolve within hours of feeding. Failure to thrive/poor weight gain (<10 g/day in young infants), weight loss, anemia, hypoproteinemia, and hypoalbuminemia are seen in patients with chronic FPIES, who might need a longer period of food avoidance for symptom resolution (days to weeks).
Feeding and growth issues — In a retrospective review of 203 patients with FPIES, 23.3 percent reported food aversion, and, compared with patients without food aversion, they were more likely to have multiple food triggers (36.4 versus 14.2 percent), have a wheat trigger (13.6 versus 2.1 percent), and have a family history of food allergy (45.4 versus 28.4 percent) [59]. Patients with poor weight gain compared with normal weight gain were more likely to have chronic FPIES (31.6 versus 10.2 percent), multiple food triggers (42.1 versus 16.8 percent), and triggers of CM (42.1 versus 18.6 percent) and banana (26.3 versus 5.4 percent). The risk of developing food aversion was higher in patients with FPIES triggered by three or more foods compared with patients with FPIES with one or two food triggers (adjusted odds ratio [OR] 3.07, 95% CI 1.38-6.82). The risk of poor weight gain was higher in FPIES triggered by CM (adjusted OR 3.41, 95% CI 1.21-9.63) and banana (adjusted OR 7.63, 95% CI 2.10-27.80).
Atypical FPIES — Some patients with FPIES have mixed immunologic reactions to the food(s) causing their FPIES symptoms. Up to 25 percent of infants and children fulfilling the clinical diagnostic criteria for FPIES have or develop IgE antibodies to the trigger food. These patients are referred to as having atypical FPIES because the disorder is primarily considered a cell-mediated allergy [9,66]. They tend to have a more protracted course of FPIES and have the potential for developing symptoms of IgE-mediated allergy (eg, anaphylaxis) in addition to FPIES. In one study, for example, 7 of 17 children with CM-induced FPIES who developed CM IgE positivity progressed to immediate allergic reactions ranging from mild symptoms to anaphylaxis [23]. (See 'Allergy testing' below.)
Atopic disease — FPIES is associated with atopic comorbidities. Approximately 30 percent of infants with FPIES develop atopic diseases, such as atopic dermatitis (25 to 65 percent), asthma (3 to 20 percent), or allergic rhinitis (20 percent) [9,12]. In one study, 39 percent of the children with FPIES had concurrent sensitization (positive IgE test) to other foods [23]. Family history of atopic diseases is present in 40 to 80 percent of patients, including a family history of food allergy in approximately 20 percent [9].
In a population–based US survey, among children with physician-diagnosed FPIES (n = 261), 65.3 percent (55.2 to 74.2 percent) had more than one parent-reported IgE-mediated food allergy, 25.2 percent (18.5 to 33.4 percent) had physician-diagnosed asthma, 9.6 percent (5.8 to 15.5 percent) had atopic dermatitis/eczema, and 32.59 percent (24.4 to 41.9 percent) had allergic rhinitis [16]. Among adults with physician-diagnosed FPIES (n = 113), 42.5 percent (31.6 to 51.3 percent) had more than one comorbid physician-diagnosed IgE-mediated food allergy, 37.4 percent (26.7 to 49.5 percent) had physician-diagnosed asthma, 22.3 percent (13.8 to 34 percent) had atopic dermatitis/eczema, and 31.1 percent (21.5 to 42.7 percent) had allergic rhinitis.
In a birth cohort from the US, atopic comorbidity was higher in patients with FPIES compared with healthy children (atopic dermatitis, 20.6 versus 11.7 percent; IgE-mediated food allergy, 23.8 versus 4 percent; asthma, 26.6 versus 18.4 percent; allergic rhinitis, 28. versus 16.7 percent) [17].
Nonatopic gastrointestinal comorbidities — Patients with FPIES have higher rates of non-IgE-mediated gastrointestinal comorbid disorders. In a cohort of 203 patients from four Boston hospitals, 23.2 percent of patients had a past medical history of physician-diagnosed food protein–induced allergic proctocolitis, and 36 percent had diagnosis of gastroesophageal reflux [59]. In a population-based study in US, eosinophilic esophagitis (EoE) diagnosis was reported by 5.4 percent of children and 1.8 percent of adults with FPIES compared with the general population estimate of 0.16 and 0.18 percent, respectively [16,67].
FPIES in adults — FPIES usually starts in the first year of life, but it can also develop in older children and adults. Prevalence of adult FPIES remains obscure, although a population-based survey of US households described patient-reported, physician-diagnosed FPIES in 0.22 percent of adults [16]. In one study, 20 percent of US adults reporting allergic reactions to shrimp had no detectable shrimp-specific IgE and presented with exclusive gastrointestinal symptoms [68]. In another study, 17 of 203 (8.4 percent) patients with FPIES identified through electronic review of 5,112,203 records were adults. The median ages of onset and diagnosis for adult-onset FPIES were 33.0 (IQR 22.1-46.3) and 45.0 (IQR 35.0-51.0) years, respectively, indicating a significant delay in recognition of FPIES symptoms in adults [59].
FPIES in older children and adults usually presents as severe abdominal pain within one to four hours of food ingestion, followed by emesis and diarrhea [56,68]. In extreme cases, loss of consciousness has been reported. Patients tolerated the food regularly beforehand. However, no clear inciting event has been identified as leading to the development of FPIES. Adult FPIES is more common in females than in males, whereas in children there is no female predominance.
FPIES in older children and adults is typically triggered by seafood. Other foods, such as CM, HE, and wheat, have also been reported in smaller case series [69]. In adults with seafood FPIES, overall 60 percent react to a single food group [56,68]. Fifty percent of patients with fish FPIES react to a shellfish (crustacean or mollusk), 40 percent with crustacean FPIES react to a mollusk, and 55 percent with mollusk FPIES react to crustacean and/or fish.
Burden of FPIES in caregivers — Caregivers of children with FPIES reported worse health-related quality of life (HRQoL) than those with IgE-mediated food allergy [70]. Female caregivers had worse HRQoL than male caregivers. Caregivers of children with both solid and liquid FPIES reported worse HRQoL than those with a single trigger food. A larger study of 410 caregivers using multiple validated measures found a high psychosocial burden among caregivers and affected children [71]. On the Food Allergy Quality of Life – Parental Burden (FAQL-PB) questionnaire, caregivers reported the highest levels of burden in restaurant choice, vacation plans, and social engagement. Caregivers reported moderate stress and worry. Caregiver confidence in the ability to manage their child's food allergy was significantly lower in caregivers of children with FPIES compared with IgE-mediated food allergy. There was a positive correlation among caregiver HRQoL, stress, worry, and anxiety, and these correlated negatively with food allergy self-efficacy. Avoiding a greater number of food groups was associated with lower caregiver HRQoL, lower food allergy self-efficacy, and higher total anxiety among preschoolers and elementary school-aged children. CM FPIES was also associated with a lower caregiver food allergy-related self-efficacy and HRQoL and higher stress. Further studies are needed in more diverse populations and studies designed to improve self-efficacy in caregivers.
Laboratory and radiographic findings — The common laboratory and radiographic findings are reviewed below and summarized in the table (table 1). Most of these studies are not performed as part of the initial diagnostic evaluation for FPIES, although some may have been performed as part of the evaluation for the patient's presenting symptoms (eg, vomiting and diarrhea, failure to thrive). (See 'Diagnosis' below.)
Blood tests — Laboratory studies reveal anemia, hypoalbuminemia, and an elevated white blood cell count with a left shift and eosinophilia in patients with chronic FPIES [72]. Thrombocytosis (platelets >500 x109/L) was found in 65 percent of acute FPIES episodes with a recorded white blood cell count in one series [12]. Peripheral blood neutrophil counts are usually elevated in positive challenges (acute FPIES), peaking at six hours and returning to baseline within 24 hours. Metabolic acidosis (mean pH 7.03 in one series) and methemoglobinemia have been reported in both acute and chronic FPIES [60]. Transient methemoglobinemia was reported in approximately one-third of infants with severe reactions and acidemia in one series, with some requiring methylene blue and bicarbonate treatment [60]. Methemoglobinemia may be caused by severe intestinal inflammation and reduced catalase activity resulting in increased nitrites. Food-specific IgE testing is discussed below. (See 'Allergy testing' below.)
Stool studies — In young infants with chronic FPIES with diarrhea, results from stool examination were nonspecific, showing occult blood, polymorphonuclear neutrophils, eosinophils, Charcot-Leyden crystals, and reducing substances [72]. Stool contained frank or occult blood, mucus, sheets of leukocytes and eosinophils, and increased carbohydrate content in patients with diarrhea from acute FPIES [61].
Gastric juice studies — Symptoms, such as severe vomiting and bloody diarrhea, and results of intestinal biopsies both indicate the presence of gastrointestinal inflammation in FPIES. Thus, gastric juice analysis was performed in infants with suspected CM FPIES at baseline and three hours after an oral food challenge (OFC) in one series to look for early signs of inflammation occurring with OFC [73]. An elevated level of gastric juice leukocytes, with >10 leukocytes/hpf, was seen in 15 of 16 positive challenges after three hours, including two infants without early symptoms of emesis or lethargy, and was not seen in eight control infants with negative challenges.
Gastric juice is obtained by placing a nasogastric tube and aspirating gastric fluid. Gastric juice analysis is a research test that is a potential confirmatory test in patients with equivocal OFC results. However, it needs further validation in larger groups of patients and may not be a practical test in every setting.
Histology — Endoscopies with biopsies were more frequently performed in symptomatic infants with CM and/or soy FPIES prior to the establishment of clinical diagnostic criteria. These endoscopies revealed friable mucosa with rectal ulceration and bleeding [9]. Biopsies showed varying degrees of villous atrophy, tissue edema, crypt abscesses, and an inflammatory cell infiltrated with increased lymphocytes, eosinophils, and mast cells [38,74-76]. Immunohistochemical studies showed plasma cells displaying IgM and IgA [77,78].
Radiographic features — Radiologic studies are not part of the routine diagnostic work-up for FPIES but were performed in some older studies. In one series of infants with FPIES and chronic diarrhea, rectal bleeding, and/or failure to thrive, abdominal radiographs showed air fluid levels, nonspecific narrowing and thumb-printing of the rectum and sigmoid, and thickening of the plicae circulares in the duodenum and jejunum with excess luminal fluid [79]. Distension of small bowel loops and thickening of the wall of jejunum distal to Treitz's ligament with diffuse subserosal bleeding were reported in patients who underwent laparotomy for suspected ileus. Intramural gas seen on abdominal radiographs may lead to the misdiagnosis of necrotizing enterocolitis (NEC) [9,12]. Resolution of radiologic abnormalities after dietary restriction has been documented [9].
Allergy testing — Overall, the majority of patients have negative skin prick tests and undetectable serum food-specific IgE at diagnosis [10,13,21,23,24,37]. Approximately 20 percent of patients with solid-food FPIES and 18 to 30 percent with CM or soy FPIES have detectable food-specific IgE to the same food, and up to 39 percent of children with FPIES have sensitization (positive IgE test) to different foods. (See 'Atypical FPIES' above.)
Atopy patch testing (APT) was evaluated in 19 infants aged 5 to 30 months with challenge-confirmed FPIES [80]. APT correctly predicted 28 of 33 outcomes of OFCs. All positive OFCs had a positive APT, although five patients with positive APT did not react upon OFC. These results have not been confirmed by other studies. Thus, further evaluation is required to determine the role of APT in the diagnosis of FPIES.
DIAGNOSIS — The diagnosis of FPIES is based upon the history, constellation of typical clinical symptoms with clinical improvement following withdrawal of the suspected causal protein, exclusion of other etiologies, and, if necessary, results of an oral food challenge (OFC) (table 2) [61,81]. Our diagnostic approach is consistent with international consensus guidelines on diagnosis and management of FPIES published in 2017 [6]. There are no laboratory and radiographic findings specific to FPIES. However, obtaining a complete blood count with differential during an acute presentation may be useful in that an elevated white blood cell count with a left shift is suggestive of FPIES or sepsis. In addition, an elevated methemoglobin level in a child that appears ashen, gray, or cyanotic and very ill also suggests the diagnosis of FPIES. (See 'Blood tests' above and 'Infections' below and 'Congenital methemoglobinemia' below.)
Endoscopy and biopsy are not routinely performed but may be indicated to rule out other pathology of the gastrointestinal tract in cases where symptoms are unusually severe and do not resolve with bowel rest or amino acid-based formula. Skin prick testing and/or serum food-specific IgE testing is usually performed as part of the evaluation to rule out sensitization to particular foods and possible concomitant IgE-mediated disease. (See 'Differential diagnosis' below and 'Laboratory and radiographic findings' above.)
Infants often present with multiple reactions and extensive evaluations before the diagnosis of FPIES is considered, especially when FPIES is caused by solid foods [12,13]. Similarly, adults also report experiencing multiple reactions prior to diagnosis [56,68]. Nonspecific symptoms and lack of definitive diagnostic tests can contribute to the delay in diagnosis. Delayed diagnosis of solid-food FPIES may also be due to the perception that rice, oats, and vegetables have low allergenic potential and are not usually suspected as triggers of allergic reactions.
Oral food challenge — OFC is the gold standard for diagnosis of FPIES. However, infants do not usually require confirmatory challenges for initial diagnosis if they have a classic history (table 1) and symptoms resolve after removal of the offending food from the diet. Clinician-supervised OFCs are necessary, however, if the history is unclear and a specific food trigger has not been identified, if the time course symptoms are atypical (eg, severe emesis within minutes of food ingestion in the absence of food-specific IgE), or if the child has persistent symptoms on an allergen-restricted diet, with the goal in this case of identifying the relevant food(s) and avoiding unnecessary food restrictions.
An OFC for FPIES is generally considered a high-risk procedure. In a patient with prior severe FPIES reactions, an OFC should be conducted in a setting where intravenous access can be secured, rapid fluid resuscitation given if a reaction occurs, and prolonged observation can occur if necessary. An inpatient setting is the most appropriate for FPIES OFCs, but outpatient settings equipped with resuscitation capabilities and with access to a laboratory (for neutrophil counts) can be used. Performing FPIES OFCs in an intensive care unit is unnecessary unless the patient has a history of near fatality with an episode [34]. Intravenous access may not be needed in a patient with history of mild reactions to a large amount of food or when introducing potentially coreactive foods (no prior exposures) [82,83].
How FPIES OFCs are conducted varies among centers, but the principles of FPIES challenges are:
●The patient is observed for at least four to six hours after the last ingested dose and an age-appropriate amount is eaten (either as a single dose or as split doses).
●A serum food specific-IgE or skin prick test may be performed shortly prior to or at the time of the OFC to rule out IgE-sensitization because there is a risk of transformation to IgE-mediated allergy (particularly to cow's milk [CM] or hen's egg [HE]; IgE transformation to rice/oats has not been reported).
●Intravenous access should be at least available.
●Ondansetron (oral, intravenous, intramuscular) may be effective in reducing the severity of a reaction; there is a lack of evidence about the efficacy of glucocorticoids for acute reactions.
A protocol for conducting OFCs for FPIES is outlined in the table (table 3) [7,21,32,61,82,84-86]. This is one of several protocols used in practice.
In an alternative approach, food challenges were performed by administering one-third of a serving size for age as a single dose, followed by a four-hour observation period [82]. Patients were discharged with detailed written instructions for home , with an increase in the dose every 3 days over 9 to 12 days until the full serving size for age has been reached. Out of 169 challenges, 30 (18 percent) were positive, with 17 during initial challenge and 13 during home dosing. Most reactions during the initial challenge were treated with intravenous fluids, but hypotension was uncommon. The 13 patients who reacted during home dosing tolerated the initial challenge in the office but developed delayed reactions at home to CM (five), soy (three), rice (two), oat (one), corn (one), and peanut (one). Most reactions were characterized by delayed diarrhea, although three had vomiting. One patient with vomiting presented to the emergency department (ED) but did not require additional treatment. All occurred later in the day of initial challenge or within the first few days of home dosing. Seven patients had a history of acute FPIES, five patients with chronic FPIES, and one had never ingested the triggering food.
Symptoms typically resolve within two to four hours with standard management (table 3 and algorithm 1). Results from a case series of five consecutive patients suggest that ondansetron hydrochloride is an effective therapy that hastens symptom resolution in many patients who develop profuse vomiting and systemic symptoms (eg, pallor, irritability, lethargy, confusion) during an OFC [87]. These patients received intravenous ondansetron (dose of 0.08 to 0.16 mg/kg) in addition to normal saline fluid replacement. All patients had complete resolution of symptoms within 10 to 15 minutes. One patient had initially received oral ondansetron with only partial resolution of symptoms. Another patient had a recurrence of symptoms an hour after improving that responded to a second dose of ondansetron. In an Italian study, five children (age 13 months to four years) who reacted during FPIES food challenge experienced prompt resolution of symptoms within 15 minutes after receiving intramuscular ondansetron injection [88]. However, during the most severe OFC reactions, ondansetron efficacy may be limited, and intravenous fluid resuscitation is necessary [82].
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of FPIES is extensive and includes food-allergic disorders, infectious diseases, intestinal obstruction due to anatomic or functional etiologies, severe gastroesophageal reflux disease, and metabolic, neurologic, and cardiac diseases. A comprehensive differential diagnosis is presented in the table (table 4).
Gastrointestinal food allergy disorders — The gastrointestinal disorders caused by food allergy that may have a presentation similar to FPIES include both IgE-mediated (eg, anaphylaxis), mixed (eg, eosinophilic gastrointestinal disorders), and non-IgE-mediated (eg, allergic proctocolitis) disorders.
Allergic food protein-induced proctocolitis and enteropathy — Cow's milk (CM) and soy are the most common food proteins implicated in these non-IgE-mediated gastrointestinal food hypersensitivities. Skin prick testing and serum food-specific IgE are usually negative in these conditions.
●Food protein-induced proctocolitis – This benign, transient condition typically begins in the first few months of life with blood-streaked stools. These infants are well appearing and thriving, unlike the typical infant with FPIES. Over one-half of infants with proctocolitis are exclusively breastfed. Mild anemia and, rarely, hypoalbuminemia may be present. Eosinophilic infiltration of colonic biopsies is prominent, and peripheral blood eosinophilia is occasionally seen. (See "Food protein-induced allergic proctocolitis of infancy".)
●Food protein-induced enteropathy – This non-IgE-mediated inflammatory response to food causes small bowel injury, leading to malabsorption, intermittent vomiting, diarrhea, failure to thrive, and, rarely, bloody stools [89-93]. It is similar to celiac disease (also known as gluten-sensitive enteropathy), although less severe. Clinical manifestations seen in FPIES that are not typically seen in patients with food protein-induced enteropathy are lethargy, pallor, dehydration, abdominal distension, hypotension, and hypothermia.
Food protein-induced enteropathy is usually induced by CM protein and is most likely to occur in infants fed unmodified (nonformula) CM prior to nine months of age. It has also been described in response to other foods, including soy, hen's egg (HE), rice, poultry, fish, or shellfish. In some cases, the onset coincides with an episode of gastroenteritis [94]. Anemia and hypoalbuminemia may be present but not methemoglobinemia or acidemia, which can also help differentiate it from FPIES.
The diagnosis is suspected based upon the clinical features and is confirmed by endoscopy with biopsy of the proximal small intestine that demonstrates patchy villous atrophy with a cellular infiltrate. Celiac disease should be specifically excluded by antibody testing (typically IgA antibodies to tissue transglutaminase [IgA-tTG]) and histologic features. The histopathologic features of food protein-induced enteropathy are similar to those of celiac disease (villous blunting, intraepithelial lymphocytes, and crypt hyperplasia) but are generally less severe.
Food protein-induced enteropathy is managed by strict elimination of the offending protein, just as celiac disease is managed by elimination of gluten. The disorder generally resolves spontaneously after two years of age [91].
Eosinophilic gastrointestinal disorders — Eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis are mixed pathophysiology disorders. Sensitization to food allergens is more common in the eosinophilic gastrointestinal disorders than in FPIES, with approximately one-half of patients having detectable food-specific IgE antibodies. Disease onset ranges from a few days of age to adulthood. Symptoms are usually chronic, evolving over days to weeks following food exposure, and may include nausea, vomiting, poor appetite, early satiety, abdominal pain, and diarrhea with blood or mucus. The course is insidious, chronic, and not characterized by acute episodes of severe, repetitive vomiting or lethargy. Difficulty swallowing and food impaction may be the presenting symptom in teenagers and adults with EoE. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Eosinophilic gastrointestinal diseases".)
Anaphylaxis — Anaphylaxis may present with acute onset of repetitive vomiting, diarrhea, and/or lethargy, usually within minutes to one to two hours following food ingestion. However, these manifestations occur in association with other symptoms (table 5) that are absent in FPIES. Cardiovascular shock may develop, but, unlike in FPIES, it usually ensues within minutes of exposure and is mostly responsive to treatment with intramuscular epinephrine. (See "Anaphylaxis: Emergency treatment" and "Anaphylaxis: Confirming the diagnosis and determining the cause(s)" and "Food-induced anaphylaxis" and "Anaphylaxis in infants".)
Infections — Gastrointestinal viral or bacterial (Salmonella, Shigella, Campylobacter, Yersinia) infections can also present with acute vomiting, diarrhea, and dehydration. Patients with FPIES will not have a history of fever or sick contacts. However, this history may also be absent in patients' acute viral illness. Often, it is the recurrence of repetitive emesis hours after ingestion of a particular food that points to food intolerance and not an acute microbial illness. (See "Acute viral gastroenteritis in children in resource-abundant countries: Clinical features and diagnosis" and "Approach to the infant or child with nausea and vomiting" and "Diagnostic approach to diarrhea in children in resource-abundant settings".)
Sepsis should be considered in patients who present with acute dehydration and lethargy. Hypotension and/or an elevated white blood cell count with a left shift support this diagnosis (table 6). Patients with FPIES do not present with a fever or respiratory symptoms and typically recover rapidly with vigorous rehydration alone. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)" and "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)
Necrotizing enterocolitis — Necrotizing enterocolitis (NEC) shares a number of possible presenting features with FPIES, including lethargy, poor feeding, vomiting, diarrhea, shock, and abdominal distension. Systemic and abdominal signs and symptoms seen in patients with NEC that are not typical of FPIES include apnea, respiratory failure, temperature instability, and gastric retention [95]. Intramural gas on abdominal radiograph can be seen in both NEC and FPIES, whereas peripheral blood eosinophilia is more common in FPIES compared with NEC [96]. (See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis".)
Intestinal obstruction — There are reports of exploratory laparotomy performed when acute FPIES was mistaken for ileus [79]. Both conditions improve with bowel rest and intravenous hydration and may be associated with an elevated white blood cell count, but, in FPIES, there is usually a history of recurrent episodes upon food reexposure. (See "Causes of acute abdominal pain in children and adolescents" and "Emergency evaluation of the child with acute abdominal pain" and "Intussusception in children".)
Other gastrointestinal disorders — A number of other gastrointestinal conditions may lead to severe projectile emesis (eg, pyloric stenosis), chronic emesis with poor weight gain (eg, gastroesophageal reflux disease), or abdominal distension, severe emesis, and failure to thrive (eg, Hirschsprung disease). Very-early-onset inflammatory bowel disease manifests with abdominal pain, diarrhea, bloody stools, and failure to thrive. In contrast to FPIES, there is no history of recurrence of symptoms upon food reexposure. (See "Infantile hypertrophic pyloric stenosis" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents" and "Management of gastroesophageal reflux disease in children and adolescents" and "Congenital aganglionic megacolon (Hirschsprung disease)".)
Metabolic disorders — Metabolic disorders can present acutely with episodic vomiting, dehydration, and lethargy and chronically with failure to thrive. They should be considered in the differential diagnosis if metabolic acidosis is present. Patients with metabolic disorders may have other associated features, such as hypoglycemia, hyperpnea, hematologic abnormalities (eg, anemia, neutropenia, thrombocytopenia), liver dysfunction (eg, organomegaly, jaundice), kidney disease, and developmental delay. Hyperammonemia is a common finding in patients with a metabolic disorder, although the ammonia level can be normal in patients who are not acutely ill. (See "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features" and "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management".)
Congenital methemoglobinemia — Congenital methemoglobinemia should be considered if methemoglobin levels are elevated. However, unlike patients with FPIES, most patients with congenital methemoglobinemia are asymptomatic or may only complain of headache and easy fatigability. Patients with the rarer type II disease have severe developmental abnormalities and failure to thrive. (See "Methemoglobinemia".)
INITIAL MANAGEMENT — Management consists of elimination of the offending food from the diet and an emergency treatment plan for acute episodes due to accidental exposures.
Dietary elimination — The triggering food(s) should be completely eliminated from the diet. A casein hydrolysate-based (hypoallergenic) formula is recommended in the infant with cow's milk (CM) FPIES if breastfeeding is not possible or the infant is exclusively formula fed due to frequent concomitant CM and soy FPIES. In the rare case of FPIES in the nursing infant, the mother should completely eliminate the triggering food(s) from her diet. Infants presenting with chronic symptoms due to CM or soy usually improve within 3 to 10 days of switching to a casein hydrolysate-based formula with or without temporary intravenous fluids [9]. Approximately 10 to 20 percent may require an amino acid-based formula [97]. (See "Management of food allergy: Avoidance" and "Management of food allergy: Nutritional issues".)
Many children with IgE-mediated cow's milk allergy (CMA) and hen's egg allergy (HEA) can tolerate these allergens in baked goods. This approach has not been extensively studied in FPIES, although one Italian study documented tolerance of baked hen's egg (HE) in 77 percent of children with FPIES to HE at the mean age of 30.2 months [54]. The concern is that baking does not alter sequential epitopes that would continue to be recognized by T cells, presumed to be the effector cells of allergic inflammation in FPIES. Thus, we suggest that patients with FPIES triggered by CM or HE avoid all forms of milk/dairy or egg and that tolerance to baked forms of these allergens is evaluated during a formal, clinician-supervised oral food challenge (OFC).
Introduction of new foods — Introduction of green vegetables and then fruits at four to six months of age instead of cereals is suggested because approximately one-third of infants with CM or soy FPIES develop solid-food FPIES and reactions to rice and other grains represent the most common types of solid-food FPIES (table 7) [6,13,98]. However, the decision regarding when to introduce higher-risk solid foods is best left to the discretion of the treating clinician given the paucity of evidence. Introduction of CM and soy in these infants may be attempted after one year of age (preferably under clinician 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 in the same group [7]. These recommendations are based upon a single-center clinical experience and may change as more data become available.
Emergency treatment plan — An emergency treatment letter that outlines the clinical features and management of acute FPIES should be provided to the patient/caregiver for presentation to an emergency department (ED) clinician. The emergency letter template can be accessed at the website of the International FPIES Association, as well as through the reference [7]. (See "Shock in children in resource-abundant settings: Initial management" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)
The emergency treatment for acute FPIES is reviewed in the algorithms (algorithm 2 and algorithm 1). There are no studies to support a particular protocol. In general, the child should be taken to the ED for evaluation and intravenous fluid administration if the episode is severe, manifesting with multiple episodes of projectile emesis, lethargy, and a pale or ashen appearance. Most patients with severe disease are also treated with a glucocorticoid. Ondansetron is used to control emesis in children over six months old with moderate-to-severe symptoms.
Children who develop dehydration, tachycardia, and hypotension should receive methylprednisolone as well as any necessary supportive therapy, such as oxygen or vasopressors to maintain blood pressure. The use of glucocorticoids is based upon the presumption that a cellular inflammatory response is the primary etiology of the reaction, although no studies have been conducted to confirm the efficacy of glucocorticoids in this setting. Epinephrine is used in patients with shock, but, anecdotally, it has not been helpful in resolution of other acute FPIES symptoms [63]. (See 'Pathogenesis' above.)
Small case series have reported that intravenous or intramuscular ondansetron administered at the onset of acute FPIES symptoms elicited during a supervised OFC was effective in treating emesis and abdominal pain [87,88]. Ondansetron is a serotonin receptor antagonist approved for prophylaxis and treatment of chemotherapy-induced nausea and emesis in patients older than six months. It is increasingly used for managing emesis due to a variety of causes in children, such as viral gastroenteritis or otitis media. Ondansetron inhibits peripheral and central activity of the vagus nerve. Empiric use of intravenous or intramuscular ondansetron is an option in the management of acute FPIES in a medical facility (algorithm 1). The efficacy of ondansetron for managing acute FPIES outside of a medical setting has not been studied. (See 'Oral food challenge' above.)
Patients with mild reactions of one to two episodes of emesis may be rehydrated carefully at home (algorithm 2). The exception is children who have had severe FPIES reactions in the past. These children should also be taken to the ED immediately.
NATURAL HISTORY — Cow's milk (CM) and soy FPIES resolve in a majority of patients by age three years. However, patients with solid-food FPIES may have a more protracted course. Factors associated with a slower acquisition of tolerance include concomitant detectable food-specific IgE and older age at both initial episode and diagnosis [23,99]. Age at resolution of FPIES for a particular food also varies by population. An oral food challenge (OFC) is used to determine if FPIES has resolved.
Milk and soy FPIES — The Korean cohort showed 64 percent resolution by 10 months; the Israeli birth cohort showed 90 percent resolution by age three years; the mean age at resolution was 24 months in the Italian series; and a retrospective Australian series reported 88 percent resolution by three years of age for CM [10,13,21,37,73,99]. In contrast, the median age of resolution of CM FPIES was 13.8 years in a cohort of 160 patients at the author's institution in the United States. However, the median age of resolution was 5.1 years among those with undetectable CM IgE, whereas none of the patients with detectable CM IgE had resolution of CM FPIES while in the study [23]. In addition, only 25 percent of soy FPIES resolved by age three years in the United States study, while, in the Korean cohort, 92 percent of children showed resolution of soy FPIES by 10 months [13,73]. This difference may be explained by the higher proportion of subjects with detectable food-specific IgE levels and atopic dermatitis in the United States study compared with the Israeli and Korean studies.
Solid-food FPIES natural history — In the studies on solid-food FPIES at the author's institution in the US, resolution by age three years occurred in 67 percent for vegetables, 66 percent for oat, and 40 percent for rice [12,13]. In the Australian series, resolution by three years of age was demonstrated in 87 percent for rice but only 12.5 percent for hen's egg (HE) and 25 percent for fish [99]. A Spanish series found 50 percent resolution at approximately 40 months for HE, 50 months for rice, and 54 months for fish [100]. Complete resolution to rice was seen by approximately 57 months and 75 percent resolution at 60 months for fish and 63 months for HE. The mean age of resolution for solid foods and soy in the Italian series was 53 months of age [37].
FOLLOW-UP EVALUATION — An oral food challenge (OFC) is also used to determine whether FPIES has resolved before the food is reintroduced into the diet. The recommended timing and frequency of oral rechallenges to determine resolution of disease are uncertain, and the decision is at the discretion of the treating clinician. Factors to consider when making this decision include the trigger food, whether there is concomitant IgE sensitization, and population data on resolution of the particular food, if available. We typically perform follow-up challenges every 18 to 24 months in patients without recent reactions [7]. However, others advise undertaking the follow-up challenge sooner: after 12 months of age for cow's milk (CM) and between 6 to 8 months of age for soy [73]. Further studies are needed to establish the optimal timing of follow-up challenges. (See 'Natural history' above.)
The follow-up evaluation should include testing for food-specific IgE prior to the OFC because patients initially presenting with or later developing food-specific IgE antibodies are at risk for persistent FPIES. Determination of when and how to perform a follow-up OFC in the small proportion of patients that develop positive skin prick tests and/or detectable food-specific IgE levels should also take into consideration the possibility of an acute IgE-mediated reaction. A modified OFC protocol with more incremental food-dose administration and availability of appropriate medications, such as epinephrine and an antihistamine, is recommended in these cases [66]. (See "Oral food challenges for diagnosis and management of food allergies".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy" and "Society guideline links: Food protein-induced enterocolitis syndrome (FPIES)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Bloody stools in children (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Age of onset and common triggers – Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE) mediated food allergy that primarily presents in infancy but may occur in older children and adults. The most common food triggers are cow's milk (CM) and soy formulas, although FPIES can also be caused by solid foods. (See 'Epidemiology' above and 'Pathogenesis' above.)
●Clinical features – FPIES manifests as profuse, projectile, repetitive vomiting, often with diarrhea, leading to dehydration and lethargy within one to four hours following food ingestion in the acute setting or frequent, watery diarrhea; intermittent vomiting; weight loss; and failure to thrive in a chronic form in young infants. The common laboratory and radiographic findings are reviewed in the table (table 1). (See 'Clinical features' above.)
●Diagnosis – The diagnosis of FPIES (table 2) is based upon the history, constellation of typical clinical symptoms (table 1) with clinical improvement following withdrawal of the suspected causal protein, exclusion of other etiologies, and, if necessary, results of an oral food challenge (OFC) (table 3). (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis of FPIES includes food-allergic disorders, infectious diseases, intestinal obstruction due to anatomic or functional etiologies, severe gastroesophageal reflux disease, and metabolic, neurologic, and cardiac diseases (table 4). (See 'Differential diagnosis' above.)
●Initial management – Initial management consists of elimination of the offending food from the diet and an emergency treatment plan for acute episodes due to accidental exposures (algorithm 2 and algorithm 1). (See 'Initial management' above.)
●Natural history and follow-up – CM and soy FPIES resolve in a majority of patients by age three to five years. However, patients with solid-food FPIES and/or those with concomitant detectable food-specific IgE may have a more protracted course. The recommended frequency of oral rechallenges to determine resolution of disease is uncertain, and the decision is at the discretion of the treating clinician. In our practice, we usually perform these OFCs approximately every 18 to 24 months. (See 'Natural history' above and 'Follow-up evaluation' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
