Clinical Disorders and Clinical Manifestation of Food Allergy

Food hypersensitivities develop in genetically predisposed individuals, presumably when oral tolerance fails to develop normally or breaks down. IgE-mediated reactions develop when food-specific IgE antibodies residing on mast cells and basophils come in contact with and bind circulating food allergens and activate the cells to release potent mediators and cytokines. As depicted in number of IgE-, cellular-, and mixed IgE– and cell-mediated food hypersensitivity disorders have been described. There is little evidence to implicate antigen-antibody complex–mediated hypersensitivity in food-related disorders.

In addressing possible food-induced allergic disease, the clinician must consider a variety of adverse reactions to foods that are not food allergies, especially because more than 20% of adults and children alter their diets for perceived adverse reactions/allergies. Adverse reactions that are not classified as food allergies include host-specific metabolic disorders (eg, lactose intolerance, galactosemia, and alcohol intolerance), a response to a pharmacologically active component (eg, caffeine, tyramine in aged cheeses triggering migraine, and histaminic chemicals in spoiled dark-meat fish resulting in scombroid poisoning masquerading as an allergic response), or toxins (eg, food poisoning). Additionally, psychologic (food aversion and anorexia nervosa) or neurologic (eg, auriculotemporal syndrome manifested by a facial flush from tart foods or gustatory rhinitis manifested by rhinorrhea from hot or spicy foods) responses can mimic food allergies

It is conceptually and diagnostically helpful to categorize food-induced allergic disorders based on immunopathology among those that are and are not mediated by IgE antibodies. Disorders with an acute onset of symptoms after ingestion are typically mediated by IgE antibody. Food-specific IgE antibodies arm tissue mast cells and blood basophils, a state termed sensitization. On re-exposure, the causal food proteins bind to the IgE antibodies specific for them and trigger the release of mediators, such as histamine, that cause the symptoms. Another group of food hypersensitivity disorders are subacute or chronic and are mediated primarily by T cells. A third group of chronic disorders attributed to food allergy are variably associated with detectable IgE antibody (IgE-associated/cell-mediated disorders). The features of a spectrum of the most common food-induced allergic disorders categorized by pathophysiology. The table does not include disorders such as recalcitrant childhood gastroesophageal reflux, constipation, and irritable bowel syndrome, which are sometimes attributed to food allergy. Detection of IgG antibodies to foods is not considered diagnostic of food allergy. However, Heiner syndrome, a rare infantile disorder characterized by pulmonary hemosiderosis triggered by milk protein, is associated with increased milk-specific IgG antibodies. Celiac disease and the related skin disorder dermatitis herpetiformis can be considered food allergies because an immune response to gluten in grains, such as wheat, rye, and barley, is responsible, but these disorders are not discussed further here. Dietary (food) protein–induced enteropathy is another malabsorption syndrome, but unlike celiac disease, it is usually caused by cow’s milk, is transient, is not associated with malignancy or dermatitis, and, for unclear reasons, has been rarely described in the past decade. Although symptoms of mucous and bloody stools in breast-fed infants have typically been attributed to dietary proctitis/proctocolitis caused by immune responses to maternal ingestants, such as cow’s milk, studies have recently emphasized that alternative causes, such as infection or other inflammatory disorders, should be considered. Thus empiric maternal dietary interventions should be undertaken with consideration that alternative explanations might exist, and retrials of the avoided allergen can be considered shortly after resolution of symptoms if other signs of allergy are absent. Lastly, contact dermatitis has also been attributed to foods, particularly with occupational exposure.

Food hypersensitivity disorders

IgE mediated
Gastrointestinal Oral allergy syndrome, gastrointestinal anaphylaxis
Cutaneous Urticaria, angioedema, morbilliform rashes and flushing
Respiratory Acute rhinoconjunctivitis, bronchospasm (wheezing)
Generalized Anaphylactic shock
Mixed IgE and cell mediated
Gastrointestinal Allergic eosinophilic esophagitis, allergic eosinophilic gastroenteritis
Cutaneous Atopic dermatitis
Respiratory Asthma
Cell mediated
Gastrointestinal Food protein–induced enterocolitis, food protein–induced proctocolitis, food protein–induced enteropathy syndromes, celiac disease
Cutaneous Contact dermatitis, dermatitis herpetiformis
Respiratory Food-induced pulmonary hemosiderosis (Heiner syndrome)

Gastrointestinal food hypersensitivity reactions

The number of gastrointestinal food hypersensitivities have been described. As indicated above, the pollen-food allergy syndrome (oral allergy syndrome) is elicited by a variety of plant proteins that cross-react with airborne allergens, especially birch, ragweed, and mugwort pollens.32 Patients with ragweed allergy might react to fresh melons and bananas, patients with grass pollen allergy might have symptoms when ingesting raw tomatoes, and patients with birch pollen allergy might have symptoms after the ingestion of raw potatoes, carrots, celery, apples, pears, hazelnuts, and kiwi. Because the allergens responsible for these reactions are easily broken down by heat or gastric enzymes, most patients only experience allergic symptoms in the oral and pharyngeal mucosa. Gastrointestinal anaphylaxis typically presents as acute nausea, colicky abdominal pain, and vomiting and generally occurs with allergic manifestations in other target organs.1

 Gastrointestinal food hypersensitivities

Disorder Mechanism Symptoms Diagnosis
Pollen-food allergy syndrome (oral allergy syndrome)
IgE mediated
Mild pruritus, tingling, and/or angioedema of the lips, palate, tongue, or oropharynx; occasional sensation of tightness in the throat and rarely systemic symptoms
Clinical history and positive SPT responses to relevant food proteins {prick-plus-prick method}; ±oral challenge—positive with fresh food, negative with cooked food
Gastrointestinal anaphylaxis
IgE mediated
Rapid onset of nausea, abdominal pain, cramps, vomiting, and/or diarrhea; other target organ responses (ie, skin, respiratory tract) often involved
Clinical history and positive SPT responses or RAST results;±oral challenge
Allergic eosinophilic esophagitis
IgE mediated and/or cell mediated
Gastroesophageal reflux or excessive spitting-up or emesis, dysphagia, intermittent abdominal pain, irritability, sleep disturbance, failure to respond to conventional reflux medications
Clinical history, SPTs, endoscopy and biopsy, elimination diet and challenge
Allergic eosinophilic gastroenteritis
IgE mediated and/or cell mediated
Recurrent abdominal pain, irritability, early satiety, intermittent vomiting, FTT, and/or weight loss
Clinical history, SPTs, endoscopy and biopsy, elimination diet and challenge
Food protein–induced proctocolitis
Cell mediated
Gross or occult blood in stool; typically thriving; usually presents in first few months of life
SPT responses negative; elimination of food protein → clearing of most bleeding in 72 h; ±endoscopy and biopsy; challenge induces bleeding within 72 h
Food protein–induced enterocolitis
Cell mediated
Protracted vomiting and diarrhea (±bloody) not infrequently with dehydration; abdominal distention, FTT; vomiting typically delayed 1-3 h after feeding
SPT responses negative; elimination of food protein → clearing of symptoms in 24-72 h, challenge → recurrent vomiting within 1-2 h, ∼15% have hypotension
Food protein–induced enteropathy, celiac disease (gluten-sensitive enteropathy)
Cell mediated
Diarrhea or steatorrhea, abdominal distention and flatulence, weight loss or FTT, ±nausea and vomiting, oral ulcers
Endoscopy and biopsy IgA; elimination diet with resolution of symptoms and food challenge; celiac: IgA anti-gliadin and anti-transglutaminase antibodies

source:  J Allergy Clin Immunol.2003;111(suppl):S540-7.

Cutaneous food hypersensitivity reactions

IgE, cellular, and mixed IgE and cellular reactions to foods can induce a variety of cutaneous hypersensitivity disorders. Acute urticaria and angioedema are among the most common symptoms of food-induced allergic reactions, although the exact prevalence of these reactions is unknown. Acute contact urticaria caused by food (eg, meats, vegetables, and fruits) also is common. Food allergy is infrequently the cause of chronic urticaria and angioedema (symptoms lasting >6 weeks).

Cutaneous food hypersensitivities

Disorder Mechanism Symptoms Diagnosis
Acute urticaria and angioedema IgE mediated Pruritus, hives, and/or swelling Clinical history; SPTs or RAST; ±challenge
Chronic urticaria and angioedema IgE mediated Pruritus, hives, and/or swelling of >6 wk duration Clinical history; SPTs or RAST; elimination diet; challenge
Atopic dermatitis IgE and cell mediated Marked pruritus; eczematous rash in classic distribution Clinical history; SPTs; CAP-System FEIA (ie, quantitative IgE); elimination diet and food challenges
Contact dermatitis Cell mediated Marked pruritus; eczematous rash Clinical history; patch test
Dermatitis herpetiformis Cell mediated Marked pruritus; papulovesicular rash over extensor surfaces and buttocks Skin biopsy (IgA deposition); IgA anti-gliadin and anti-transglutaminase antibodies; ±endoscopy

source: J Allergy Clin Immunol.2003;111(suppl):S540-7.

Respiratory food hypersensitivity reactions

Food allergy can induce a number of disorders in the respiratory tract, as depicted in Table V. Acute respiratory symptoms caused by food allergy generally represent isolated IgE-mediated reactions, whereas chronic respiratory symptoms represent a mix of IgE- and cell-mediated reactions. Isolated rhinoconjunctivitis is rarely the result of a food-induced allergic reaction, although it frequently occurs in association with other food allergy symptoms. Asthma is an uncommon manifestation of food allergy, although acute bronchospasm is usually seen with other food-induced symptoms.70 However, airway hyperreactivity and worsening of asthma also can be induced in the absence of marked bronchospasm after the ingestion of small amounts of food allergens in sensitized subjects.71 Interestingly, food allergy recently was found to be a major risk factor for severe life-threatening asthma. Roberts reported that about one half of asthmatic children requiring intubation for severe asthma had food allergy compared with about 10% of asthmatic patients seen at the same hospital. Vapors or steam containing proteins emitted from cooking food (eg, fish) can induce asthmatic reactions and even anaphylaxis. It has been estimated that about 1% of asthma in adults might involve reactions to inhalational exposures to food, especially in the workplace. Similarly, particulate matter, such as peanut dust in airplanes, can induce allergic reactions, whereas the smell of peanut butter, primarily organic solvents, is not likely to induce allergic symptoms. Food-induced asthmatic symptoms should be suspected in patients with refractory asthma and a history of atopic dermatitis, gastroesophageal reflux, food allergy, or feeding problems as an infant or a history of positive skin test responses or reactions to a food. Heiner’s syndrome is a rare form of food-induced pulmonary hemosiderosis typically caused by cow’s milk.

Respiratory food hypersensitivities

Disorder Mechanism Symptoms Diagnosis
Allergic rhinoconjunctivitis IgE mediated Periocular pruritus, tearing, and conjunctival erythema, nasal congestion, rhinorrhea, sneezing Clinical history, SPTs, elimination diet, food challenge
Asthma IgE and cell mediated Cough, dyspnea, wheezing Clinical history, SPTs, elimination diet, food challenge
Heiner’s syndrome ? Recurrent pneumonia, pulmonary infiltrates, hemosiderosis, iron-deficiency anemia, FTT Clinical history, peripheral eosinophilia, milk precipitins (if caused by milk), ±lung biopsy, elimination diet

source  J Allergy Clin Immunol.2003;111(suppl):S540-7.

Food-induced allergic disorders

Immunopathology Disorder Key features Additional immunopathology Typical age Most common causal foods Natural course
IgE antibody dependent (acute onset)
Triggered by ingestion or direct skin contact (contact urticaria); food commonly causes acute (20%) but rarely chronic (2%) urticaria
Children > adults
Primarily major allergens
Depending on food
Oral allergy syndrome (pollen–food related)
Pruritus, mild edema confined to oral cavity Uncommonly progresses beyond mouth (∼7%) or anaphylaxis (1% to 2%) Might increase after pollen season
Sensitization to pollen proteins by the respiratory route results in IgE that binds certain homologous, typically labile food proteins (in certain fruits/vegetables (eg, apple Mal d 1 and birch bet v 1)
Onset after pollen allergy established (adult > young child)
Raw fruit/vegetables Cooked forms tolerated Examples of relationships: birch (apple, peach, pear, carrot), ragweed (melons)
Might be long-lived and vary with seasons
Rhinitis, asthma
Symptoms might accompany a food-induced allergic reaction but rarely an isolated or chronic symptom Symptoms might also be triggered by inhalation of aerosolized food protein
Infant/child > adult, except for occupational disease (eg, baker’s asthma)
General: major allergens Occupational: wheat, egg, and seafood, for example
Depending on food
Rapidly progressive, multiple organ system reaction can include cardiovascular collapse
Massive release of mediators, such as histamine, although mast cell tryptase levels not always increased Key role of platelet-activating factor
Any but more commonly peanut, tree nuts, shellfish, fish, milk, and egg
Depending on food
Food-associated, exercise-induced anaphylaxis
Food triggers anaphylaxis only if ingestion followed temporally by exercise
Exercise is presumed to alter gut absorption, allergen digestion, or both
Onset more commonly later childhood/adult
Wheat, shellfish, and celery are most described
Presumed persistent
IgE antibody associated/cell-mediated (delayed onset/chronic)
Atopic dermatitis
Associated with food in ∼35% of children with moderate-to-severe rash
Might relate to homing of food-responsive T cells to the skin
Infant > child > adult
Major allergens, particularly egg and milk
Typically resolves
Eosinophilic gastroenteropathies
Symptoms vary on site(s)/degree of eosinophilic inflammation Esophageal: dysphagia and pain Generalized: ascites, weight loss, edema, and obstruction
Mediators that home and activate eosinophils play a role, such as eotaxin and IL-5
Likely persistent
Cell-mediated (delayed onset/chronic)
Dietary protein enterocolitis
Primarily affects infants Chronic exposure: emesis, diarrhea, poor growth, and lethargy Re-exposure after restriction: emesis, diarrhea, and hypotension (15%) 2hours after ingestion
Increased TNF-α response, decreased response to TGF-β
Cow’s milk, soy, rice and oat
Usually resolves
Dietary protein proctitis
Mucus-laden, bloody stools in infants
Eosinophilic inflammation
Milk (through breast-feeding)
Usually resolves

Reference :

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  • Meyer S, van Liempt E, Imberty A, van Kooyk Y, Geyer H, Geyer R, et al. DC-SIGN mediates binding of dendritic cells to authentic pseudo-LewisY glycolipids of Schistosoma mansoni cercariae, the first parasite-specific ligand of DC-SIGN. J Biol Chem. 2005;280:37349–37359
  • Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2009;123:426–433
  • Anna Nowak-Węgrzyn, Hugh A. Sampson. Future therapies for food allergies. Journal of Allergy and Clinical Immunology March 2011 Vol. 127, Issue 3, Pages 558-573
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  • Stephan Steckelbroeck, Barbara K. Ballmer-Weber, Stefan Vieths. Potential, pitfalls, and prospects of food allergy diagnostics with recombinant allergens or synthetic sequential epitopes. Journal of Allergy and Clinical Immunology June 2008 Vol. 121, Issue 6, Pages 1323-1330
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