Immediate Hypersensitivity

Food Allergy

Clinical Findings

Immediate hypersensitivity IgE-mediated allergic reactions to foods commonly occur within 2 hours of ingestion and are much less common in adults as a de novo food allergy than in children.

Typical reactions include a combination of emesis, diarrhea, urticaria with or without angioedema, bronchial hypersensitivity, and hypotension.

A serum tryptase may be elevated during anaphylactic reactions within a few hours after the exposure.

The most common systemic food allergies are caused by milk, egg, wheat, soy, fish, shellfish, peanuts, and tree nut allergens.

Shellfish, peanuts, and tree nuts are the most common causes of food anaphylaxis in adults; milk and egg allergies are more common in children but often resolve by adulthood.

Laboratory Tests

Diagnosis of food allergy is based on a correlative history, skin tests, and serum specific IgE tests.

There is no role for specific IgG or IgA testing for evaluating food immediate hypersensitivity.

Because of frequent false-positive IgE tests the use of indiscriminate screening of IgE panels to foods is not recommended; oral food challenge with a reproducible immediate hypersensitivity reaction remains the gold standard for diagnosis. Food challenge, however, should only be conducted by an experienced provider in a setting equipped to treat anaphylaxis.

Differential Diagnosis

Other IgE-mediated food reactions include oral allergy syndrome and hypersensitivity to alpha-gal (galactose-alpha-1,3-galactose). Oral allergy syndrome and pollen-associated food allergy syndrome result from cross-reactivity between certain food and pollen proteins. Affected individuals have known seasonal pollen allergies (most commonly tree pollens) and experience itching of the oral mucosa upon ingestion of cross-reactive raw fruits and vegetables. In contrast to systemic food allergy, symptoms are mostly limited to the oropharynx.

Treatment

Management of food allergy involves strict avoidance of the food and guaranteed access to epinephrine autoinjectors.

The use of oral immunotherapy to treat food allergy in children and adolescents, should only be performed by an experienced allergist immunologist.

Venom Allergy

Most systemic allergic reactions to insect stings are caused by honeybees, vespids (yellow jackets, hornets, wasps, honeybee), and fire ants.

Systemic anaphylactic reactions can occur after stinging events at any age. Patients at highest risk for anaphylaxis from subsequent stings are those who have had a history of recent or severe reactions, or both; thus, the risk of a systemic reaction declines over elapsed time since the last sting.

If a systemic allergy is suspected because symptoms include generalized urticaria, anaphylaxis, angioedema, wheezing, or diarrhea, refer the patient to an allergist for confirmative venom allergy testing; initiation of venom immunotherapy is commonly recommended. In the interim, patients should be given self-administrated epinephrine for those with continuing exposure.

Anaphylaxis

Anaphylaxis is the most serious and potentially life-threatening manifestation of mast cell and basophil mediator release. The National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network definition of anaphylaxis and criteria for diagnosis are shown in the following table:

Presentation	Time to Onset of Symptoms	Clinical Manifestations
Criterion 1: Acute onset of illness	Minutes to 2-3 hours	One of the following combinations of symptoms: – Skin or mucosa, or both1 with Respiratory compromise2 or hypotension or end-organ dysfunction3
Criterion 2: After exposure to likely allergens	Minutes to 2-3 hours	Involvement of two or more of the following systems: – Skin or mucosa, or both1 – Respiratory compromise2 – Hypotension or end-organ dysfunction3 – Persistent GI symptoms4
Criterion 3: After exposure to known allergens	Minutes to 2-3 hours	Involvement of the cardiovascular system: – Hypotension

Anaphylaxis is defined under these circumstances:

(1) an allergen exposure followed by the acute onset of illness involving skin or mucosal tissue and either respiratory compromise or hypotension (systolic blood pressure < 90 mm Hg or 30% < known baseline);

(2) a likely allergen exposure followed by the acute onset of at least two of these conditions: skin or mucosal tissue involvement, respiratory compromise, hypotension, and persistent GI symptoms;

or (3) a known allergen exposure followed by hypotension.

IgE-dependent anaphylaxis is an acute syndrome initiated by a new allergen exposure after a prior exposure has sensitized the patient with anti-allergen IgE antibodies; IgE-mediated anaphylaxis cannot occur on first-time exposure to allergens like medications, insect venoms, latex, and foods.

Conversely, other anaphylactic reactions (sometimes called “anaphylactoid”), such as radiocontrast media, certain medications (most NSAIDs, opioids, and vancomycin), and COVID mRNA vaccine reactions, are due to different immunologic mechanisms and can occur with first-time exposure.

Clinical Findings

Symptoms and Signs

Symptoms and signs typically start to occur within 30 minutes of initial exposure but may rarely appear up to several hours later. These include:

(1) skin manifestations (typically urticaria, flushing, blotchy rashes, and pruritus);

(2) respiratory distress (wheezing, stridor, bronchospasm, and airway angioedema);

(3) GI symptoms (cramping, emesis, and diarrhea [especially in food allergy]);

and (4) hypotension.

⚠️ Anaphylaxis is potentially fatal, especially if untreated. ⚠️

Laboratory Findings

Laboratory evaluation obtained shortly after onset of symptoms can support a diagnosis of anaphylaxis but should not take the place of expedient treatment.

Elevated serum tryptase within 4–6 hours following onset of anaphylaxis is most useful because it is a specific biomarker of mast cell degranulation.

Plasma histamine generally peaks 30 minutes after onset of symptoms, making it difficult to obtain during peak levels.

Referral to an allergist is necessary because of concern for future reactions and need for appropriate education and intervention. Specific serum IgE or skin testing to suspected allergens may be performed optimally 4–6 weeks after a severe reaction; this delayed testing is to avoid falsely negative testing during a post-reaction “refractory” period where IgE consumed during anaphylaxis has not yet been regenerated. The positive predictive value of these tests depends highly on a suggestive temporal relationship to suspected allergen exposure.

Treatment

Administration of intramuscular epinephrine (0.01 mg/kg of a 1:1000 [1 mg/mL] solution, maximum 0.5 mg in adults) at the onset of suspected anaphylaxis is the cornerstone of therapy and should not be delayed. There is no absolute contraindication to administering intramuscular epinephrine in the setting of anaphylaxis.

Supportive measures, such as oxygen, intravenous fluids and, if required, airway management are also appropriate.

Adjunctive therapies may include antihistamines, bronchodilators, and corticosteroids. Self-administered epinephrine at the earliest signs of recurrence can be life-sparing, whereas antihistamines and corticosteroids have limited value in reversing anaphylaxis.

When to Refer

Cutaneous or skin prick allergen testing produces a localized pruritic wheal (induration) and flare (erythema) that is maximal at 15–20 minutes. Such testing is used most commonly to diagnose allergic respiratory disease (rhinitis and asthma) and IgE-mediated allergy to food, drugs (penicillins), and hymenoptera venom. Allergen extracts are available for pollens, fungi, animal danders, and dust mites and are appropriately selected for the patient’s geographic area.