Key Facts

Severe allergic reactions are common presentations to emergency departments. The key clinical decision is whether the reaction constitutes anaphylaxis (requiring adrenaline) or a non-anaphylactic allergic reaction (managed with antihistamines and observation).

Epidemiology

Allergic disease affects approximately 30-40% of the UK population. ED attendances for allergic reactions have doubled over the past 20 years. Acute urticaria is the most common allergic presentation. Angioedema without anaphylaxis accounts for approximately 100,000 ED attendances annually.

Aetiology

• IgE-mediated (type I): Food, drugs, insect stings, latex — rapid onset (minutes to hours)
• Non-IgE mediated: ACEi-induced angioedema (bradykinin-mediated), contrast media reactions
• Hereditary angioedema: C1 esterase inhibitor deficiency — autosomal dominant
• Chronic spontaneous urticaria: Autoimmune (anti-IgE or anti-FcεRI antibodies) in many cases

Pathophysiology

Allergic reactions involve mast cell and basophil degranulation releasing histamine, leukotrienes, and prostaglandins. In non-anaphylactic reactions, these mediators cause localised effects (urticaria, angioedema) without systemic cardiovascular or respiratory compromise. HAE is mediated by excess bradykinin production due to C1 esterase inhibitor deficiency — this is NOT a histamine-mediated process.

Acute Urticaria

• Raised, itchy wheals (hives) on any body surface
• Each wheal lasts <24 hours, new ones may appear
• Resolves spontaneously or with antihistamines

Angioedema (Without Anaphylaxis)

• Deep swelling of eyelids, lips, tongue, hands, feet, genitalia
• Non-pitting, often asymmetric
• May affect larynx (stridor) — monitor closely
• ACEi-induced: Occurs in ~0.5% of users; may develop after years of use

Hereditary Angioedema

• Recurrent episodes of angioedema WITHOUT urticaria
• Family history (autosomal dominant)
• Often triggered by trauma, stress, infection, oestrogens
• Does NOT respond to antihistamines, steroids, or adrenaline

Red Flags

• Tongue/laryngeal swelling with voice change or stridor — imminent airway obstruction
• Any sign of ABC compromise — escalate to anaphylaxis protocol
• Recurrent angioedema without urticaria — consider HAE (check C4, C1 inhibitor)
• ACEi use with angioedema — stop ACEi permanently (can switch to ARB with caution)

Bedside

• Clinical assessment: Identify whether anaphylaxis criteria are met (ABC involvement)
• Observations: SpO2, BP, HR, RR — monitor for progression
• Airway assessment: Voice change, stridor, tongue protrusion

Bloods

• Serum tryptase: If anaphylaxis suspected (take at 1h and 24h)
• C4 level: Screening test for HAE — low C4 between and during attacks
• C1 esterase inhibitor level and function: Confirm HAE diagnosis
• Specific IgE / RAST: For suspected allergens (food, drug, venom)
• FBC: Eosinophilia may suggest allergic/parasitic cause

Imaging

• Not routinely required; lateral soft tissue neck X-ray if concern about laryngeal oedema

Special Tests

• Skin prick testing: Specialist allergy clinic — 6 weeks post-reaction
• Drug provocation testing: For drug allergy confirmation
• Autologous serum skin test: For chronic spontaneous urticaria (autoimmune)

Non-pharmacological

• Allergen avoidance: Identify and remove trigger
• Patient education: Provide written allergy action plan
• MedicAlert bracelet: For severe allergies
• Dietitian referral: If food allergy (ensure nutritional adequacy)

Pharmacological

Acute urticaria/angioedema (no ABC compromise):

• Cetirizine 10mg PO or chlorphenamine 10mg IV/IM (acute setting)
• Prednisolone 40mg PO for 3-5 days if severe or not responding
• Ranitidine 50mg IV (H2 blocker) — adjunct in severe urticaria

ACEi-induced angioedema:

• Stop ACEi permanently
• Supportive care; adrenaline/antihistamines have limited efficacy (bradykinin-mediated)
• If severe airway compromise — intubation or surgical airway
• Consider icatibant (bradykinin B2 receptor antagonist) if available

Hereditary angioedema:

• Acute attack: C1 esterase inhibitor concentrate (Berinert 20 IU/kg IV) or icatibant 30mg SC
• Prophylaxis: Danazol 200-600mg/day (androgenic side effects) or tranexamic acid 1-1.5g BD-TDS; lanadelumab SC (anti-kallikrein antibody)

Chronic urticaria (>6 weeks):

• Non-sedating antihistamine (cetirizine/loratadine) — up to 4× standard dose
• Add ranitidine or montelukast
• Omalizumab (anti-IgE) for refractory chronic spontaneous urticaria (NICE TA339)

Referral Criteria

• Suspected anaphylaxis — allergy clinic referral + auto-injector prescription
• Recurrent angioedema without urticaria — immunology (HAE workup)
• Chronic urticaria refractory to antihistamines — dermatology/allergy
• Drug allergy confirmation needed — specialist allergy service

• Acute urticaria: Self-limiting in most cases; resolves within days to weeks
• Chronic urticaria: 50% resolve within 1 year; some persist for years; omalizumab effective in ~70%
• ACEi angioedema: Resolves within 24-72 hours of stopping ACEi; rare fatalities from airway obstruction
• HAE: Lifelong condition; laryngeal attacks carry mortality risk; modern treatments have dramatically improved outcomes
• Drug allergy: Accurate documentation prevents re-exposure; most drug 'allergies' are intolerances not true IgE-mediated allergy

Distinguishing Anaphylaxis from Severe Allergic Reaction

Types of Angioedema