Anaphylaxis: Diagnosis, Emergency Algorithm, and Adrenaline

1. Definition & criteria (WAO 2020)

Anaphylaxis is an acute, systemic, potentially fatal hypersensitivity reaction characterized by rapid onset and progression. It is highly likely when any one of the following criteria is met:

1. Acute onset (minutes to hours) of skin/mucosal involvement (urticaria, lip angioedema, pruritus) plus at least one of the following: respiratory symptoms (dyspnea, bronchospasm, stridor, hypoxemia) or hypotension / signs of hypoperfusion.
2. Acute onset of ≥ 2 of the following 4 symptoms after exposure to a likely allergen: skin/mucosal involvement, respiratory compromise, cardiovascular compromise, persistent GI symptoms (vomiting, cramping).
3. Hypotension after exposure to a known allergen (systolic BP < 90 mmHg or a > 30% decrease from baseline in adults).

2. Pathogenesis

IgE-mediated reactions (food allergens, insect venoms, medications) → allergen binds to IgE on mast cells and basophils → degranulation → release of histamine, tryptase, leukotrienes, prostaglandins, PAF → vasodilation, ↑ vascular permeability, bronchospasm, hypotension. Non-immunological mechanisms (direct degranulation caused by opioids, radiocontrast media, physical exertion) were formerly termed 'anaphylactoid reactions'; WAO 2020 classifies all under 'anaphylaxis'.

3. Triggers

• Foods: nuts (peanuts, tree nuts), seafood, milk, eggs, soy, wheat, sesame.
• Hymenoptera venoms (bees, wasps).
• Medications: β-lactams, NSAIDs, neuromuscular blockers, iodinated contrast media, monoclonal antibodies.
• Latex.
• Food-dependent exercise-induced anaphylaxis (often wheat ω-5 gliadin).
• Idiopathic anaphylaxis.

4. Clinical presentation

In 10–20% of patients, cutaneous manifestations may be absent (especially in drug-induced anaphylaxis and in children) — an atypical presentation does not rule out the diagnosis.

5. Severity grading (Ring & Messmer)

• I — cutaneous symptoms only.
• II — mild-to-moderate GI/respiratory symptoms.
• III — severe bronchospasm, shock, loss of consciousness.
• IV — cardiac arrest.

6. Emergency management algorithm

Immediate actions

1. Stop exposure to the trigger (discontinue offending drug infusion, remove bee stinger).
2. Call for help, activate the resuscitation team.
3. Positioning: supine with legs elevated (unless upper airway obstruction or pregnancy is present — place in the left lateral position). If breathing is difficult — upright.
4. Epinephrine IM: 0.01 mg/kg (1:1000, i.e., 0.01 mL/kg), maximum 0.5 mg in adults and 0.3 mg in children, injected into the anterolateral thigh. Repeat every 5–15 minutes if no response.
5. Oxygen 6–10 L/min via face mask, target SpO₂ > 94%.
6. Establish venous access, infuse normal saline 20 mL/kg (bolus) in case of hypotension.

Second-line medications (after epinephrine!)

• Salbutamol 2.5–5 mg via nebulizer — for bronchospasm.
• H₁-blocker (diphenhydramine 25–50 mg IV or chloropyramine 20 mg IV) — relieves skin itching, does not halt the reaction.
• H₂-blocker (ranitidine — restricted in Russia since 2020; famotidine 20 mg IV).
• Corticosteroids (methylprednisolone 1–2 mg/kg IV or hydrocortisone 200 mg) — to prevent biphasic reactions; onset of action in 4–6 hours.
• Glucagon 1–5 mg IV — for anaphylaxis induced by β-blockers (refractory to epinephrine).
• Vasopressors (norepinephrine, dopamine) — for refractory hypotension.

7. Why epinephrine comes first

• α1 — vasoconstriction → ↑ blood pressure, ↓ edema.
• β1 — inotropic and chronotropic effects.
• β2 — bronchodilation, ↓ mast cell mediator release.
• IM injection into the thigh — faster and safer than SC or IV.
• Delay in epinephrine administration is the primary factor in mortality (studies show that > 50% of fatal cases did not receive epinephrine or received it too late).

8. Observation after resolution

• Mild reaction — 4–6 h of observation.
• Moderate-severe — 12–24 h (risk of biphasic reaction).
• Anaphylactic shock — ICU.
• Serum tryptase — diagnostic confirmation (drawn 30 min – 4 h from onset; repeat at 24 h as baseline).

9. Secondary prevention

• Allergological workup in 4–6 weeks (skin tests, specific IgE).
• AIT — for hymenoptera venom (80–90% efficacy).
• Trigger avoidance, patient and family education.
• Medical alert bracelet indicating the allergen.
• Epinephrine auto-injector (EpiPen, Anapen — limited availability in Russia) — 2 doses for high-risk patients.
• Training in self-care and caregivers of children.

10. Special situations

• Pregnancy: epinephrine is used without restrictions; pregnancy category C, but the risk of maternal death outweighs it.
• β-blockers: reduce epinephrine efficacy; glucagon + additional doses of epinephrine.
• Children: epinephrine dose 0.01 mg/kg up to max 0.3 mg; auto-injectors 0.15 mg (up to 25 kg), 0.3 mg (> 25 kg).
• Systemic mastocytosis: rule out in patients with recurrent anaphylaxis without a clear trigger (elevated baseline tryptase).

11. Differential diagnosis

• Vasovagal syncope (bradycardia + pallor, no urticaria).
• Panic attack.
• Acute myocardial infarction.
• Pulmonary embolism.
• Carcinoid syndrome.
• Scombroid fish poisoning (tuna, mackerel — histamine).
• Hereditary angioedema (C1-inhibitor deficiency) — does not respond to epinephrine; C1-esterase inhibitor, icatibant are used.

12. FAQ

Why intramuscularly instead of subcutaneously?
I.m. injection into the thigh achieves peak concentration faster (8 min vs 34 min s.c.), lower risk of ischemia, more precise dosing.

Can antihistamines be used instead of epinephrine?
No. They do not halt anaphylaxis; delayed administration of epinephrine is associated with mortality.

How many times can epinephrine be repeated?
Every 5–15 min if there is no effect; if > 2 doses are needed, initiate IV infusion at 0.1–1 mcg/kg/min under monitoring.

What is a biphasic reaction?
Reappearance of symptoms 1–72 h (most commonly 8–10 h) after initial resolution — occurs in 5% of patients. The rationale for prolonged observation.

Is an EpiPen needed for "mild" allergy?
Following a history of anaphylaxis — mandatory. In high-risk cases (allergy to nuts, seafood, venom, asthma) — recommended at all times.

See also: Immune cells · Pediatric asthma · Glucocorticoids · Myocardial infarction · Immunology catalog