Symptoms triggered by IgE-mediated reactions occur rapidly following ingestion of the trigger food. IgE antibodies that are specific for regions (epitopes) of food proteins arm tissue mast cells and circulating basophils. Cross-linking of the IgE antibodies by the food proteins leads to release of preformed mediators (such as histamine and platelet-activating factor) from cytoplasmic granules and transcription of inflammatory cytokines. The target organs(s) involved in the reaction define the type of food allergy . The symptoms occurring during an acute reaction can be classified as cutaneous, ocular, gastrointestinal, respiratory, or cardiovascular. A combination of these symptoms may occur.

Cutaneous manifestations of an acute food allergy reaction include erythema, hives, pruritus, flaring of eczematous lesions, and angioedema. Food allergy may account for up to 20 % of new-onset urticaria [16, 17]. Food allergies rarely cause chronic urticaria (e.g., episodes occurring regularly for 6 weeks or longer). Eczema (atopic dermatitis) can be chronically exacerbated by specific IgE-mediated food allergy , with improvement upon removal of the suspect food [18–20]. Overall, skin symptoms are the most common manifestation of IgE-mediated food allergies. Food can also induce skin symptoms by direct skin contact (contact urticaria) [21–25].

Oral allergy syndrome, also referred to as pollen food allergy syndrome, is a form of contact allergy with symptoms isolated to the oral cavity. Sensitization initially occurs from inhalation of pollens, but results in symptoms when fruits or vegetables with proteins that are homologous to the pollens are ingested. For example, birch pollen contains proteins homologous with Rosaceae fruits (e.g., apple, peach, carrot). Pruritus and mild swelling of the lips, tongue, and throat occur when specific uncooked fruits and vegetables are ingested, but heated forms are tolerated [26]. Symptoms typically last several minutes before self-resolving. While anaphylaxis associated with oral allergy has been reported, it is relatively rare [27].

Anaphylaxis is defined as “a serious allergic reaction that is rapid in onset and may cause death” [28]. Symptoms generally include a combination of the above symptoms (or respiratory or cardiac symptoms alone), with anaphylactic shock referring to signs of poor organ perfusion in addition to anaphylaxis. Anaphylaxis may result in hypotension, cardiac dysrhythmias, cardiovascular collapse, or death. In children, respiratory, cutaneous, and gastrointestinal symptoms are prominent, and the most common cause of death is respiratory compromise. Less than 1 % of anaphylaxis cases (including those not due to food ingestion) are fatal [29, 30]. In retrospective analysis, several factors appear to be associated with the severity of the allergic response. A larger quantity of food allergen ingested, concomitant alcohol consumption, and concomitant nonsteroidal anti-inflammatory drugs (NSAID) use all appear to increase the rapidity and severity of the reaction [31–34]. Concomitant ingestion of fatty foods appears to slow the rate of absorption and thus delay onset of symptoms. Risk-taking behaviors among adolescents and young adults, including increased incidents of exposure to the avoided allergen and a lack of a prompt treatment response to symptoms, conspire to contribute to the disproportionately higher number of fatal food-induced anaphylaxis in this age group [35]. In one case series of fatal food-induced anaphylactic reactions, accidental ingestion of a known food allergen was present in 87 % of cases [31]. In several cases, previous reactions to the known allergen were relatively mild, highlighting the inconsistency in severity of reactions. Having asthma is an additional risk factor for fatal anaphylaxis. Biphasic anaphylactic reactions occur in up to 20 % of cases [36]. In this scenario, a second wave of symptoms occurs 1–4 h following resolution of the initial anaphylactic reaction .

Food-dependent, exercise-induced anaphylaxis is an IgE-mediated food-induced anaphylactic reaction that occurs when vigorous exercise is performed within a few hours of food allergen ingestion. Neither exercise alone nor ingestion of the food allergen alone is sufficient to cause symptoms. While generally associated with specific causative foods (such as wheat, other grains, celery, seafood, or nuts), in some cases any food can cause the reaction when consumed in close temporal relation to exercise [37, 38]. Another uncommon syndrome of anaphylaxis is delayed anaphylaxis occurring several hours after ingestion of mammalian meat, attributed to an IgE response against a carbohydrate moiety, galactose-α-1,3-galactose (α-gal). The etiology is presumed to be related to exposure to this allergen via tick bites [39–42].

Mild IgE-mediated reactions may subside with antihistamines. However, progressive, multisystem, or severe reactions should be treated promptly with intramuscular epinephrine. Severe reactions may require multiple doses of epinephrine, intravenous fluids, oxygen, vasopressors, additional treatments, and monitoring in an acute care setting.

IgE-mediated food allergy generally appears during the first 2 years of a child’s life. The sensitivity to most allergenic foods (egg, milk, wheat, and soy) self-resolves in 85 % of children during childhood [43]. Sensitivity to peanuts, tree nuts, and seafood persists into adulthood in the large majority of affected children. Approximately, 20 % of peanut-allergic children under the age of 2 years and 10 % of children with tree nut allergy will become tolerant to those foods by the time they are of school age, however [44].

FPIES is a cell-mediated gastrointestinal food allergy that typically manifests in infancy and generally resolves by 3 years of age. In the acute form, 1–3 h after ingestion of the causative food, infants present with profuse, repetitive vomiting and may experience dehydration and lethargy. Diarrhea may occur several hours following the vomiting. In the chronic form, with continued ingestion of the allergen, infants develop weight loss and failure to thrive. Cow’s milk and soy are the most common triggers in formula-fed infants. Symptoms begin 1–4 weeks after introduction of cow’s milk or soy. Solid food FPIES is less common than milk/soy FPIES, and presents later, usually at 4–7 months of age, most often when weaning a breast-fed infant. Solid food FPIES triggers include rice, oats, barley, chicken, turkey, egg white, green peas, peanuts, sweet potatoes, white potatoes, fruits, fish, and mollusks. Of those infants diagnosed with solid food FPIES , 65 % carried a prior diagnosis of milk/soy FPIES and 80 % reacted to more than one food. Overall, 75 % of infants presenting with FPIES appear acutely ill, and 15 % become hypotensive, requiring hospitalization. Laboratory findings may include anemia, thrombocytosis, hypoalbuminemia , and an elevated white blood cell count with a left shift and eosinophilia. Transient methemoglobinemia and intramural gas have also been reported [47, 48]. Table 26.3 shows key features of FPIES. While the exact pathophysiologic mechanism for FPIES has yet to be elucidated, it is thought to be a cell-mediated disorder. Studies have shown increased levels of tumor necrosis factor-α, increased numbers of circulating blood mononuclear cells, and decreased intestinal mucosal expression of transforming growth factor-β receptors in association with FPIES [49–53].

Food-protein-induced enteropathy is characterized by vomiting, diarrhea, malabsorption, failure to thrive, and anemia in an infant [45]. Cow’s milk protein is the most likely causative agent, particularly in infants fed intact cow’s milk prior to 9 months of age. This syndrome has also been described in infants following an episode of gastroenteritis and in response to other foods, including eggs, rice, fish, shellfish, and poultry [46, 58].

Food-protein-induced allergic proctocolitis is characterized by blood and mucus in the stool of an otherwise healthy infant. Infants may be fussy or have increased frequency of bowel movements. The causative agent is usually milk in the maternal diet of a breast-fed infant, although egg, soy, and corn have been implicated as well [60]. Maternal dietary elimination of the causal agent leads to resolution of symptoms within 72 h. The problem generally resolves by 1 year of age. The causal food may be gradually reintroduced at that point, or earlier. The primary alternative explanation for these symptoms is infection.

Studies utilizing cow’s milk elimination and challenge have shown between 14 and 42 % of cases of gastroesophageal reflux in infants is attributable to cow’s milk allergy [70–75]. In these cases, the reflux generally occurs in conjunction with atopic dermatitis, diarrhea, esophagitis, or malabsorption. An elimination diet may be helpful in infants with documented cow’s milk allergy and reflux [76].

While infants with colic are not more frequently atopic than controls, [77] 44 % of children with cow’s milk allergy have colic [78, 79] . Soy and low-lactose formulas have not been successful in reducing the rate of colic, but a meta-analysis suggested a 1-week trial of hypoallergenic formula could be considered in such cases [79].

In select groups of children with chronic constipation unresponsive to laxatives, cow’s milk elimination diets resulted in resolution of constipation in 28–68 % [80, 81]. Among responders, increased frequency of atopy and IgE antibodies was noted, suggesting a possible immunologic basis for their constipation. However, the soy milk used in lieu of cow’s milk in these studies may have had a laxative effect [76].

Skin prick testing is typically performed by allergist–immunologists. The allergen is introduced by scratching the surface of the skin and observing for a wheal and flare response, which is measured. Intradermal tests are not indicated as they are too sensitive and may induce systemic allergic reactions. Larger wheal size correlates with a greater concentration of food-specific IgE and greater likelihood of clinical allergy [89–91]. The sensitivity of skin prick testing is about 90 %, the specificity is approximately 50 % [92]. The skin of infants tends to be less sensitive than that of older children, however [93]. Given the high sensitivity of skin prick testing, it is a useful test for ruling out individual allergens in patients with a low pretest probability for food allergy to those specific allergens. However, performing skin prick testing to broad arrays of foods without attention to the medical history is not recommended, as the false-positive rate is high.