10.4 Immediate-Type Allergy: Diagnostics, Anaphylaxis, Food, Venom & Drug Allergy
Key Takeaways
- First-line treatment of anaphylaxis is intramuscular adrenaline 0.01 mg/kg (maximum 0.5 mg in adults) into the anterolateral thigh, repeated after 5 minutes if needed.
- Serum tryptase is best taken about 1 to 2 hours after the onset of anaphylaxis and compared with a baseline sample taken at least 24 hours after the reaction.
- In peanut allergy, sensitisation to the storage protein Ara h 2 predicts systemic reactions, whereas Ara h 8, a Bet v 1 homologue, is linked to mild oral allergy syndrome.
- Venom immunotherapy is usually given for 3 to 5 years, and lifelong treatment is considered in patients with mastocytosis or a raised baseline tryptase after a severe sting reaction.
- Alpha-gal syndrome, triggered by tick bites, causes delayed urticaria or anaphylaxis about 3 to 6 hours after eating red meat.
10.4 Immediate-Type Allergy: Diagnostics, Anaphylaxis, Food, Venom & Drug Allergy
Allergology is part of Session 2 of the official timetable. Dermatologists in many European countries carry out allergy testing themselves, so questions test both the tests and emergency care.
Mechanism
In type I hypersensitivity, a first exposure produces allergen-specific IgE, which binds the high-affinity receptor FcεRI on mast cells and basophils (sensitisation). On re-exposure, the allergen cross-links IgE, and the cells release histamine, tryptase, leukotrienes, and prostaglandins within minutes. Symptoms include urticaria, angioedema, rhinoconjunctivitis, asthma, gut symptoms, and anaphylaxis. A late-phase reaction can follow after 4–8 hours.
Non-IgE mast cell activation (formerly "pseudoallergy") can mimic allergy. Examples are the MRGPRX2 receptor (fluoroquinolones, neuromuscular blocking agents, icatibant), NSAID cross-intolerance through COX-1 inhibition, radiocontrast media, and opioids.
Diagnostic Tests
| Test | Use and Key Points |
|---|---|
| Skin prick test (SPT) | Standardised extracts pricked into the forearm, read at 15–20 minutes; positive control histamine and negative control saline; a wheal ≥ 3 mm greater than the negative control is positive. Stop oral antihistamines several days before. Positive tests show sensitisation, which is significant only with a matching history |
| Intradermal test | More sensitive; used for drugs and venoms; higher risk of systemic reactions |
| Specific IgE | Serum test (for example ImmunoCAP); useful with extensive eczema, dermographism, or if antihistamines cannot be stopped |
| Component-resolved diagnostics | Tests IgE to individual molecules to estimate risk (see table below) |
| Basophil activation test | Flow cytometry of CD63 or CD203c after allergen exposure; helpful for drugs, venoms, and foods in specialist centres |
| Oral food or drug provocation test | The gold standard; done under supervision with resuscitation available; contraindicated after SJS/TEN or DRESS |
| Serum tryptase | Taken about 1–2 hours after the start of a reaction and compared with a baseline taken at least 24 hours later. A peak above (1.2 × baseline) + 2 ng/mL supports mast cell activation. A raised baseline suggests mastocytosis or hereditary alpha-tryptasaemia |
Important Allergen Components
| Component | Source | Meaning |
|---|---|---|
| Ara h 2 (2S albumin) | Peanut | High risk of systemic reactions |
| Ara h 8 | Peanut (Bet v 1 homologue) | Cross-reactivity with birch pollen; usually mild oral allergy syndrome |
| Bet v 1 | Birch pollen | Pollen-food syndrome with apple, hazelnut, carrot, stone fruits |
| Lipid transfer proteins (for example Pru p 3, peach) | Plant foods | Stable proteins; severe reactions, common in Southern Europe |
| Tri a 19 (omega-5 gliadin) | Wheat | Food-dependent exercise-induced anaphylaxis |
| Tropomyosin | Shellfish, mites | Cross-reactivity between crustaceans and house dust mites |
| Galactose-alpha-1,3-galactose (alpha-gal) | Red meat, cetuximab | Delayed anaphylaxis 3–6 hours after red meat, after tick bites |
| Api m 1; Ves v 1, Ves v 5 | Honeybee; wasp (yellow jacket) | Separate true double sensitisation from cross-reactivity when choosing venom immunotherapy |
Anaphylaxis
Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction. It is likely when skin or mucosal symptoms appear suddenly with airway, breathing, or circulation problems, or when two or more organ systems are involved after likely allergen exposure. Skin signs are absent in a minority of cases.
Emergency Treatment
- Call for help, and remove the trigger if possible.
- Intramuscular adrenaline (epinephrine) 1 mg/mL into the anterolateral thigh: 0.01 mg/kg, maximum 0.5 mg in adults. Repeat after 5 minutes if there is no improvement.
- Lie the patient flat with legs raised (or sitting if breathless; left side if pregnant). Do not stand them up suddenly.
- High-flow oxygen, IV fluids for hypotension, and inhaled bronchodilators for wheeze.
- Antihistamines and corticosteroids are second-line. They do not treat airway obstruction or shock.
- Observe for a possible biphasic reaction, take tryptase samples, and refer to an allergist.
- Prescribe two adrenaline auto-injectors with training and a written action plan. Adult devices usually contain 0.3 mg or more; 0.15 mg devices are for small children.
Risk factors for severe reactions: uncontrolled asthma, older age, cardiovascular disease, mastocytosis, beta-blocker or ACE inhibitor use, and cofactors such as exercise, alcohol, NSAIDs, and infection.
Food Allergy
- IgE-mediated: milk, egg, peanut, tree nuts, sesame, fish, and shellfish. Symptoms begin within minutes to 2 hours.
- Pollen-food syndrome: itching of the mouth and throat from raw fruit and vegetables in pollen-allergic patients (for example birch and apple). Cooking usually destroys these labile proteins.
- Management: avoidance, clear labelling advice, an emergency plan, and adrenaline for those at risk. Oral immunotherapy for peanut is available for children in the EU under specialist supervision.
- Early introduction of peanut and egg in infancy reduces the risk of developing allergy in high-risk infants.
Hymenoptera Venom Allergy
- Large local reaction: swelling over 10 cm lasting more than 24 hours, next to the sting. The risk of a later systemic reaction is low.
- Systemic reaction: from generalised urticaria to anaphylaxis.
- Diagnosis: skin tests (prick and intradermal), specific IgE and components, and baseline tryptase. A raised baseline tryptase or mastocytosis predicts severe reactions.
- Venom immunotherapy (VIT): indicated after systemic reactions beyond the skin, and in adults with generalised skin reactions when risk factors are present. It is highly effective (wasp VIT more than honeybee VIT). It is usually given for 3–5 years, and lifelong VIT is considered in mastocytosis, very severe reactions, or ongoing high exposure (beekeepers).
Immediate Drug Allergy
- Beta-lactams: most patients labelled "penicillin allergic" can tolerate penicillin after assessment. Delabelling by skin testing and drug provocation reduces the use of broad-spectrum alternatives. Cross-reactivity with cephalosporins depends mainly on similar R1 side chains (for example amoxicillin with cefadroxil). Cross-reactivity with carbapenems is about 1%.
- NSAIDs: most reactions are cross-intolerance from COX-1 inhibition (NSAID-exacerbated respiratory disease, cutaneous disease, or NSAID-induced urticaria and angioedema). Selective COX-2 inhibitors are usually tolerated. A smaller group react to a single NSAID through an allergic mechanism.
- Perioperative anaphylaxis: neuromuscular blocking agents, antibiotics, chlorhexidine, patent blue dye, and latex.
Latex Allergy
Immediate IgE allergy to natural rubber latex proteins (Hev b allergens) mainly affected healthcare workers and children with spina bifida. It is linked to the latex-fruit syndrome (banana, avocado, kiwi, chestnut). Delayed contact allergy to rubber accelerators (thiurams, carbamates) is a different, type IV problem.
Allergen Immunotherapy (AIT)
AIT gives increasing doses of the allergen subcutaneously (SCIT) or sublingually (SLIT) for about 3 years. It induces allergen-specific IgG4 blocking antibodies, regulatory T cells, and IL-10, producing long-lasting tolerance. Indications include allergic rhinitis with or without asthma (grass, birch, house dust mite) and venom allergy. Uncontrolled asthma is a contraindication, and SCIT injections need about 30 minutes of observation afterwards.
Ten minutes after a wasp sting, a 40-year-old man develops widespread urticaria, throat tightness, wheeze, and a blood pressure of 80/50 mmHg. What is the first drug to give?
A 50-year-old woman had anaphylaxis after a honeybee sting. Her baseline serum tryptase, taken 2 weeks later, is 24 ng/mL, and skin examination shows reddish-brown macules that urticate when rubbed. How does this affect venom immunotherapy?
A 25-year-old woman with birch pollen allergy has itching of the mouth after eating raw apple and raw peanuts. Component testing shows IgE to Ara h 8 and Bet v 1, with negative Ara h 2. What does this pattern suggest?
A 45-year-old forester has had two episodes of urticaria and hypotension at night, about 4 hours after eating beef for dinner. He recalls many tick bites. What is the most likely diagnosis?