Background
Adverse food reactions can be broadly classified into 2 categories. The first category consists of immunologically-mediated adverse reactions to foods; these reactions are unrelated to any physiologic effect of the food or food additive. These reactions include disorders mediated by immunoglobulin E (IgE) antibodies (eg, IgE-mediated reaction to peanuts), which begin during or soon after exposure to the food, and others resulting from non–IgE-mediated mechanisms (eg, non–IgE-mediated reactions such as protein-induced enterocolitis syndrome), which generally take several hours to evolve.
The second category is food intolerance. These reactions include any adverse physiologic response to a food or food additive that is not immunologically mediated (eg, lactose intolerance, bacterial food poisoning).
Pathophysiology
Allergic reactions to food are IgE-mediated or non–IgE-mediated. Immune responses mediated by specific IgE antibodies are the most widely recognized mechanism of food hypersensitivity. Patients with atopy produce IgE antibodies to specific epitopes of the food allergen. These antibodies bind to high-affinity IgE receptors on circulating basophils and tissue mast cells present in the skin, gastrointestinal tract, and respiratory tract. Subsequent allergen exposure binds two adjacent IgE antibodies, resulting in receptor cross-linking and intracellular signaling that initiates the release of numerous mediators, including histamine, prostaglandins, leukotrienes, chemotactic factors, and cytokines. The effects of these mediators on surrounding tissues result in vasodilatation, smooth muscle contraction, and mucus secretion, which, in turn, are responsible for the spectrum of clinical symptoms observed during allergic reactions to food.
Food allergens are typically water-soluble glycoproteins resistant to heating and proteolysis with molecular weights of 10-70 kd. These characteristics facilitate the absorption of these allergens across mucosal surfaces. Numerous food allergens are purified and well-characterized, such as peanut Ara h1, Ara h2, and Ara h3; chicken egg white Gal d1, Gal d2, and Gal d3; soybean-Gly m1; fish-Gad c1; and shrimp-Pen a1. Closely related foods frequently contain allergens that cross-react immunologically (ie, lead to the generation of specific IgE antibodies detectable by skin prick or in vitro testing) but less frequently cross-react clinically. Finally, cross-reactive allergens have been identified among certain foods and airborne pollens . Conserved homologous proteins shared by pollens and foods likely account for this cross-reactivity.
Frequency
United States
General surveys report that as many as 25-30% of households consider at least 1 family member to have a food allergy. This high rate is not supported by controlled studies in which food challenges are used to confirm patient histories. The actual prevalence of food allergies is estimated to be approximately 6% in infants and children and 3.7 % in adults. Several published prospective investigations have determined the prevalence of certain common food allergies in children (eg, cow milk, 2.5%; eggs, 1.3%; peanuts, 0.8%; wheat, 0.4%; soy, 0.4%).
International
Prospective studies from several different countries indicate that approximately 2.5% of newborn infants experience hypersensitivity reactions to cow milk in the first year of life. A hypersensitivity reaction to peanuts occurs in approximately 0.5% of children in the United Kingdom. Surveys from the United Kingdom indicate that 1.4-1.8% of adults experience adverse food reactions and 0.01-0.23% of adults are affected by adverse reactions to food additives. Studies from the Netherlands demonstrate that approximately 2% of the adult Dutch population is affected.
Mortality/Morbidity
- Severe anaphylactic reactions, including death, can occur following the ingestion of food. Typical symptoms observed in a food-induced anaphylactic reaction involve the skin, gastrointestinal tract, and respiratory tract. Frequently observed symptoms include oropharyngeal pruritus, angioedema (eg, laryngeal edema), stridor, dysphonia, cough, dyspnea, wheezing, nausea, vomiting, diarrhea, flushing, urticaria, and angioedema. Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension, or a combination thereof. Food allergy has been confirmed in approximately one third of the patients with anaphylaxis presenting to the emergency department at the Mayo Clinic.
- Peanuts, tree nuts, and shellfish are the foods most often implicated in severe food-induced anaphylactic reactions, although anaphylactic reactions have been reported to a wide variety of foods.
- Risk factors for fatal food-induced anaphylaxis include (1) the presence of asthma, especially in patients with poorly controlled disease; (2) previous episodes of anaphylaxis with the incriminated food; (3) a failure to recognize early symptoms of anaphylaxis; and (4) a delay or lack of immediate use of emergency medications (eg, epinephrine, antihistamines) to treat the allergic reaction.
Race
- No predilection is known.
Sex
- No predilection is known.
Age
- In infants and children younger than 3 years, the prevalence of food allergy is approximately 6%.
- The estimated prevalence in adults is approximately 3.7%.
Medical Care
- Education
- Education is of paramount importance for patients with food allergie.
- Education is of paramount importance for patients with food allergie.
- Remember that appropriate restriction and complete avoidance of the relevant food allergen(s) is the only current effective therapy.
- Elimination of food allergen
- Once a food allergy is diagnosed, strict elimination of the offending food allergen from the diet and avoidance of any contact with the food either by ingestion, skin contact, inhalation, or injection is necessary.
- Once a food allergy is diagnosed, strict elimination of the offending food allergen from the diet and avoidance of any contact with the food either by ingestion, skin contact, inhalation, or injection is necessary.
- Elimination and strict avoidance is the only proven medical therapy for this allergic disease.
- Elimination and strict avoidance is the only proven medical therapy for this allergic disease.
- Recognize the early signs and symptoms of an allergic reaction. Keep in mind that cutaneous, gastrointestinal, and respiratory symptoms are the most common clinical manifestations of food allergy.
Consultations
- Consultation with a nutritionist or nutrition service is invaluable in the overall management. The elimination diet can be reviewed and appropriate substitutions can be recommended. Dietary deficiencies can be anticipated and prevented.
- Consultation with a gastroenterologist is also useful in the evaluation of selected patients. For example, patients presenting with possible anatomic gastrointestinal abnormalities, eosinophilic esophagitis or gastroenteritis, failure to thrive, and malabsorption syndromes may benefit from consultation with both an allergist and a gastroenterologist.
Diet
- A properly managed well-balanced elimination diet (eg, allergen restriction) can lead to resolution of symptoms and help avoid nutritional deficiencies.
- Educate the patient and family about how to properly read food labels and identify common words used for indicating the presence of the food allergen of concern (eg, casein and whey for milk).
- With elimination diets, only exclude those foods confirmed to provoke allergic reactions.
- Review obvious and hidden sources of food allergens. Be aware of the potential for exposures by routes other than ingestion, such as skin contact, inhalation, or injection.
- Anticipate potential candidates for food allergen cross-reactivity, such as the following:
- Eggs and chicken (<5%)>
- Cow milk and beef (10%)
- Cow milk and beef (10%)
- Cow milk and goat milk (>90%)
- Fish (>50%)
- Fish (>50%)
- Peanuts and related legumes (<10%)
- Soy and related legumes (<5%)
- Wheat and other grains (25%)
- Tree nuts and other nuts (>50%)
- Encourage avoidance of high-risk situations (eg, buffets, picnics), where accidental or inadvertent ingestion of food allergens can occur.
Despite following stringent avoidance measures for clinically relevant food allergens, accidental or inadvertent ingestions occur all too often. Therefore, a concise written plan for the treatment of allergic reactions resulting from accidental exposure to the food must be available to the patient. For patients with a history of a mild reaction, such as urticaria and pruritus following the ingestion of a food allergen, treatment may be limited to an oral antihistamine. However, the potential for a more severe reaction on subsequent exposures must be taken into consideration because of the possibility of the ingestion of a larger dose than previously ingested or an unexpected or unrecognized increase in the patient’s degree of sensitivity.
If the patient has significant systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection in the lateral thigh. Examples of systemic manifestations of food allergy include generalized urticaria, laryngeal edema, lower respiratory symptoms (eg, chest tightness, dyspnea, wheezing), and hypotension. Administer epinephrine to any patient with history of a severe allergic reaction as soon as ingestion of the food allergen is discovered and the first symptoms appear.
For the medical therapy of food allergen–induced allergic reactions, the use of antianaphylactic agents, antihistamines, bronchodilators, and corticosteroids in combination with the administration of intravenous fluids and oxygen (when indicated), is suggested.
Drug Category: Adrenergic agonists
Used in the emergency management of systemic allergic reactions or anaphylaxis (eg, urticaria, angioedema, bronchospasm, cardiovascular collapse). Effects are immediate and dramatic. Appropriate use of this class of medication can be lifesaving, especially in the emergency management of anaphylaxis.
| Drug Name | Epinephrine (Adrenaline, EpiPen) |
|---|---|
| Description | DOC for treating anaphylaxis. Helps decrease symptoms of anaphylaxis by increasing systemic vascular resistance, elevating diastolic pressure, producing bronchodilation, and increasing inotropic and chronotropic cardiac activity. In addition, helps reduce urticaria, angioedema, laryngeal edema, and other systemic manifestations of anaphylaxis. |
| Adult Dose | 0.3 mL SC of 1:1000 aqueous injected (usual range is 0.2-0.5 mL) q10-15min, not to exceed 3 doses; may need to decrease dose to 0.2 mL in elderly persons or those with known cardiac conditions 0.3 mL IM of 1:1000 dilution q10-15min; IV route (1:10,000) seldom used; not to exceed 0.25 mg; given very slowly and with extreme caution 0.3-mg self-injectable devices (Epi-Pen) |
| Pediatric Dose | IM dosing in children based on weight or 0.01 mL/kg IM of 1:1000 dilution; not to exceed 0.3 mL IM 1:2000 dilution q10-15min0.15-mg self-injectable devices (Epi-Pen Jr) |
| Contraindications | Documented hypersensitivity; cardiac arrhythmias, coronary artery insufficiency, or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor) |
| Interactions | Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics, ie, drugs that may sensitize the heart to arrhythmias |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Dose may be decreased in elderly patients to 0.2 mL; may cause disturbing reactions such as fear, anxiety, tenseness, restlessness, throbbing headache, weakness, dizziness, pallor, respiratory difficulty, palpitation, tachycardia, tremor, and arrhythmia; use with caution in patients with cardiovascular disease, hyperthyroidism, and diabetes; properly train patients with use of self-injectable devices; advise patients to seek medical attention if using self-injectable devices to manage allergic reactions |
Drug Category: Antihistamines (histamine-1 blockers)
Inhibit many responses to histamine. Histamine, via H1 receptors, causes smooth muscle contraction, increased capillary permeability, and formation of edema. During hypersensitivity reactions, histamine is one of the major potent mediators released. Blocking effects of this mediator with specific antihistamines is useful in emergency management of allergy symptoms.
| Drug Name | Diphenhydramine (Benadryl, Benylin) |
|---|---|
| Description | Frequently used antihistamine for management of acute allergic symptoms. Medication has significant antimuscarinic activity and pronounced tendency to induce sedation. Approximately half of those treated with conventional doses experience some degree of somnolence. |
| Adult Dose | 25-50 mg PO q6h 50-75 mg IV/IM q6h; IV drip may afford better control of symptoms (5 mg/kg/d); not to exceed 300 mg in 24 h |
| Pediatric Dose | 1-2 mg/kg/dose PO q6h 1-2 mg/kg/dose IV/IM q6h; IV drip may afford better control of symptoms (5 mg/kg/d) |
| Contraindications | Documented hypersensitivity; MAO inhibitors; glaucoma, gastrointestinal obstruction, hyperthyroidism, hypertension, and cardiovascular disease; may limit use in elderly patients |
| Interactions | Potentiates effect of CNS depressants; due to alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Adverse anticholinergic effects and drowsiness; large doses may depress respiration; use can potentially worsen glaucoma, gastrointestinal or urinary obstruction, hyperthyroidism, and hypertension; dizziness, paradoxical excitement, gastritis, and blood dyscrasias; caution with performing certain motor skills (eg, operating heavy machinery, driving a motor vehicle) |
Drug Category: Antihistamines (histamine-2 blockers)
| Drug Name | Ranitidine (Zantac) |
|---|---|
| Description | H2-receptor antagonists competitively inhibit the interaction of histamine with H2 receptors. These are highly selective and have little or no effect on H1 receptors. H2-receptor antagonists are primarily used for the management of active duodenal or benign gastric ulcer disease. They are also used in the healing of duodenal or benign gastric ulcers. |
| Adult Dose | 150 mg PO q8-12h 50 mg IV q6-8h |
| Pediatric Dose | Safety not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in renal or liver impairment and nursing mothers; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment |
| Drug Name | Cimetidine (Tagamet) |
|---|---|
| Description | H2-receptor antagonists competitively inhibit interaction of histamine with H2 receptors. These are highly selective and have little or no effect on H1 receptors. Used in hypersecretory conditions, intractable duodenal ulcers, and for prevention of upper gastrointestinal bleeding. |
| Adult Dose | 300 mg PO q6-8h 300 mg IV q6-8h |
| Pediatric Dose | <16>16 years: 20-40 mg/kg/d PO/IV |
| Contraindications | Documented hypersensitivity |
| Interactions | Can increase blood levels of theophylline, warfarin, TCAs, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Elderly patients may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur |
| Drug Name | Famotidine (Pepcid) |
|---|---|
| Description | H2-receptor antagonists competitively inhibit the interaction of histamine with H2 receptors. Highly selective and have little or no effect on H1 receptors. Used for active duodenal ulcers, maintenance of healed duodenal ulcers, and active benign gastric ulcers. Also used for gastroesophageal reflux disease and associated esophagitis. Individualize and adjust dose based on response. |
| Adult Dose | 20-40 mg PO/IV q12h |
| Pediatric Dose | <1> |
| Contraindications | Documented hypersensitivity |
| Interactions | May decrease effects of ketoconazole and itraconazole |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Reduce dose or prolong dosing interval with severe renal insufficiency (CrCl <10> |
Drug Category: Bronchodilators
Patients experiencing significant adverse respiratory symptoms as part of their food-induced allergic reaction must be managed aggressively with nebulized bronchodilators. Nebulized adrenergic agonists or bronchodilators are usually administered for treatment of bronchospasm. Supplemental oxygen can also be administered with nebulizations. In selected cases, parenteral agents may be employed to achieve sufficient bronchodilation.
| Drug Name | Albuterol (Proventil, Ventolin) |
|---|---|
| Description | Common bronchodilator used in clinical medicine. |
| Adult Dose | 2.5-5 mg (0.5 mL of 5% solution diluted to a final volume of 3 mL with 0.9% saline) nebulized over 5-15 min q20min, not to exceed 6 doses; also available in unit dose vials (3 mL of 0.083% solution) for nebulization |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; avoid excessive use with cardiac disease, arrhythmia, hypertension, hyperthyroidism, seizure disorders, labor, and delivery; not recommended for nursing mothers |
| Drug Name | Metaproterenol (Alupent, Dey-Dose, Prometa) |
|---|---|
| Description | Beta2-adrenergic agonist that relaxes bronchial smooth muscle with little effect on heart rate. |
| Adult Dose | 0.3 mL of 5% solution diluted in 2.5 mL of 0.45% or 0.9% normal saline nebulized over 5-15 min q4h |
| Pediatric Dose | 0.1-0.2 mL of 5% solution diluted in 3 mL of 0.45% or 0.9% normal saline nebulized over 5-15 min q4h |
| Contraindications | Documented hypersensitivity; arrhythmia associated with tachycardia |
| Interactions | Decreases effect of beta-receptor blockers; increases toxicity of MAOIs, TCAs, and sympathomimetics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hypertension, cardiovascular disease, congestive heart failure, hyperthyroidism, diabetes, and seizures; not recommended for nursing mothers; adverse reactions include tachycardia, headache, nervousness, dizziness, tremor, gastrointestinal upset, hypertension, paradoxical bronchospasm, and cough |
| Drug Name | Theophylline (Aquaphyllin, Aminophyllin) |
|---|---|
| Description | Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. |
| Adult Dose | 5-6 mg/kg IV loading dose in 20 mL D5W over 10-15 min, followed by a maintenance dose of 0.5-1 mg/kg/h |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, and uncontrolled seizure disorders |
| Interactions | Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance |
Drug Category: Corticosteroids
Ameliorate delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis. In severe cases of serum sickness, parenteral steroids may be beneficial to reduce inflammatory effects of this immune complex–mediated disease.
| Drug Name | Methylprednisolone (Medrol, Adlone, Solu-Medrol) |
|---|---|
| Description | For treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. |
| Adult Dose | 60-80 mg IV for 1 dose; then q6h |
| Pediatric Dose | 1-2 mg/kg/dose IV q6h; not to exceed 60-80 mg |
| Contraindications | Documented hypersensitivity; viral, fungal, or tubercular infections |
| Interactions | Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use |
| Drug Name | Hydrocortisone (Cortef) |
|---|---|
| Description | Has mineralocorticoid and glucocorticoid effects. Useful in management of inflammation caused by immune response. |
| Adult Dose | 100-200 mg IV q6-8h |
| Pediatric Dose | Not to exceed 5-10 mg/kg IV q6-8h |
| Contraindications | Documented hypersensitivity; viral, fungal, or tubercular infections |
| Interactions | Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis |
| Drug Name | Prednisone (Deltasone, Meticorten, Sterapred) |
|---|---|
| Description | Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. |
| Adult Dose | 20-40 mg PO qd with quick taper |
| Pediatric Dose | 1-2 mg/kg/d PO with quick taper; not to exceed 20-40 mg |
| Contraindications | Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease |
| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use |
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