15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions

1. Food Allergy

A named blueprint subsection. True IgE-mediated food allergy must be distinguished from food intolerance, which is far more common and is not immunologic.

Common adult food allergens: shellfish, fish, peanut, tree nuts, and, in adults with pollen sensitization, fruits and vegetables.

Diagnosis: the history drives everything. Skin prick testing and specific IgE identify sensitization, not clinical allergy — a positive test in someone who eats the food without reaction is not an allergy, and broad panel testing generates false positives that lead to unnecessary elimination diets. Oral food challenge remains the reference standard.

Distinctive syndromes:

• Pollen-food allergy syndrome (oral allergy syndrome) — itching and mild swelling of the lips and oropharynx after raw fruits or vegetables in a patient with pollen allergy, from cross-reacting heat-labile proteins. Cooked forms are tolerated, and systemic reactions are rare.
• Alpha-gal syndrome — delayed anaphylaxis 3 to 6 hours after eating mammalian meat, following a tick bite (Lone Star tick in the United States). The delay is what makes it easy to miss; the patient wakes at night with urticaria and does not connect it to dinner. It also causes reactions to cetuximab and to some gelatin-containing products.
• Food-dependent exercise-induced anaphylaxis — reaction only when the food (classically wheat) is followed by exercise.
• Eosinophilic esophagitis — a non-IgE food-driven disorder causing dysphagia and food impaction.

Management: strict avoidance of the confirmed allergen, an epinephrine autoinjector with an action plan, education on label reading and cross-contact, and referral for consideration of oral immunotherapy where appropriate.

2. Stinging Insect Hypersensitivity

Hymenoptera — honeybee, yellow jacket, hornet, wasp, fire ant.

Classify the reaction, because it determines everything that follows:

Venom immunotherapy is the single highest-yield fact here. After a systemic sting reaction in an adult, venom immunotherapy reduces the risk of a subsequent systemic reaction from roughly 30 to 60% down to a few percent, and the protection persists for years after a completed course. An adult with a systemic reaction and positive venom testing should be referred, and this is a rare instance in which a disease-modifying allergy treatment is genuinely curative.

Baseline serum tryptase should be measured in anyone with severe or hypotensive sting anaphylaxis, because an elevated level suggests clonal mast cell disease, which markedly increases risk and changes management.

3. Desensitization Therapy

An enumerated blueprint topic. Desensitization is not the same as immunotherapy.

Key point: desensitization induces temporary tolerance only while the drug is continuously present. If the drug is stopped for more than about 48 hours, the patient reverts to being allergic and must be desensitized again. Desensitization is appropriate for IgE-mediated reactions; it is contraindicated in severe delayed reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS.

The classic indication is penicillin desensitization for syphilis in pregnancy, where no adequate alternative exists.

4. Serum Sickness

An enumerated topic and a type III immune complex reaction.

• Timing: 7 to 14 days after first exposure — the delay is the diagnostic signature — or 1 to 3 days on re-exposure
• Triad: fever, rash (often urticarial or a serpiginous eruption at the sides of the hands and feet), and arthralgia, with lymphadenopathy
• Low complement (C3 and C4) with circulating immune complexes; proteinuria may occur
• Causes: heterologous antisera and antivenoms, monoclonal antibodies, and serum-sickness-like reactions from beta-lactams (notably cefaclor), sulfonamides, minocycline and bupropion

It is self-limited after withdrawal of the agent; NSAIDs and antihistamines suffice for mild disease, corticosteroids for severe cases. The delayed onset separates it from anaphylaxis, and low complement separates it from a simple drug exanthem.

5. Aspirin Idiosyncrasy and NSAID Hypersensitivity

An enumerated blueprint topic. Reactions to aspirin and NSAIDs are usually pharmacologic rather than immunologic, arising from cyclooxygenase-1 inhibition shunting arachidonic acid toward leukotriene production.

Aspirin-exacerbated respiratory disease (Samter triad)

The triad:

1. Asthma, often severe and difficult to control
2. Chronic rhinosinusitis with nasal polyposis — recurrent despite surgery
3. Respiratory reaction to aspirin and other COX-1 inhibitors — bronchospasm, profuse rhinorrhea and nasal congestion within 30 minutes to 3 hours

It typically develops in adulthood in someone who previously tolerated NSAIDs, which is why patients and clinicians dismiss the association.

Management: avoid COX-1 inhibitors; selective COX-2 inhibitors are generally tolerated, as is acetaminophen at standard doses. Aspirin desensitization followed by daily aspirin improves sinonasal outcomes and reduces polyp recurrence and is a recognized therapy — and it is also the pathway used when such a patient requires aspirin for coronary disease. Leukotriene-modifying drugs and biologics targeting type 2 inflammation are adjuncts.

Other NSAID reaction patterns: NSAID-exacerbated cutaneous disease in patients with chronic urticaria; NSAID-induced urticaria and angioedema in otherwise well patients; and single-NSAID IgE-mediated reactions, in which other chemically unrelated NSAIDs are tolerated.

6. Contrast-Related Allergy

An enumerated blueprint topic surrounded by persistent misconceptions.

Most immediate reactions to iodinated contrast are not IgE-mediated. They result from direct mast cell activation, and they range from urticaria to anaphylaxis-like reactions treated identically to anaphylaxis with epinephrine.

Myths worth explicitly rejecting:

• Shellfish allergy does not predict contrast reaction. The historical association with iodine is not immunologically valid; shellfish allergy is to tropomyosin, and iodine is not an allergen. A patient with shellfish allergy has no more contrast risk than anyone with atopy generally.
• Povidone-iodine skin reactions do not predict contrast reaction.
• The true risk factor is a prior reaction to contrast itself, along with asthma and severe atopy.

Management of a patient with prior contrast reaction:

1. Determine whether contrast is truly necessary, and whether an alternative modality (ultrasound, non-contrast CT, MRI) would answer the question
2. Use a different, low- or iso-osmolar agent where possible
3. Premedicate with corticosteroids and an antihistamine on a defined schedule before the study
4. Recognize that premedication reduces but does not eliminate breakthrough reactions, and that resuscitation capability must be available

Delayed contrast reactions — a maculopapular eruption 1 to 7 days after administration — are T-cell mediated and are managed symptomatically.

Gadolinium carries a distinct concern: nephrogenic systemic fibrosis in advanced kidney disease, though this risk is very low with modern group II agents.

7. Allergic Complications of Transfusion

A named blueprint subsection listing hemolytic transfusion reactions, transfusion-related acute lung injury, and transfusion-related urticaria and anaphylaxis. These are covered in detail in the transfusion medicine section; the allergy-specific points are:

• Isolated urticaria during transfusion is the only reaction for which the transfusion may be paused, treated with an antihistamine and cautiously resumed if symptoms resolve and no systemic features develop.
• Anaphylaxis during transfusion should prompt measurement of IgA levels, because an IgA-deficient recipient with anti-IgA antibodies can react to plasma-containing products. Such patients require washed cellular products or components from IgA-deficient donors.
• Any systemic feature — hypotension, bronchospasm, angioedema — means stop the transfusion and treat as anaphylaxis, not pause and resume.