anaphylaxis

quick recognition

• 4 systems to consider: cutaneous, respiratory, cardiovascular, gastrointestinal
• urticaria/angioedema are not required — absence does not rule out anaphylaxis
• throat tightness alone does not meet criteria unless exposed to a known/highly probable allergen
• onset typically minutes to a few hours after allergen exposure
• anaphylaxis is a clinical diagnosis — do not wait for labs to treat

diagnosis

WAO 2020 criteria

Acutely (minutes to hours) after allergen exposure, highly likely when:

Criterion 1 — skin/mucosal involvement plus any of:

• respiratory compromise (dyspnoea, wheeze, stridor, hypoxaemia)
• reduced BP or associated symptoms (syncope, incontinence, hypotonia)
• severe GI symptoms (especially after non-food allergens)

Criterion 2 — after exposure to a known or highly probable allergen:

• hypotension (SBP <90 mmHg or >30% decrease from baseline)
• bronchospasm (excluding symptoms triggered by common inhalant allergens without ingestion)
• laryngeal involvement (stridor, vocal changes, odynophagia)

NIAID/FAAN 2006 criteria

1. Cutaneous symptoms plus respiratory compromise or reduced BP
2. Two or more systems involved after exposure to a likely allergen (cutaneous, respiratory, cardiovascular, GI)
3. Reduced BP after exposure to a known allergen (SBP <90 or >30% drop)

clinical course

Pattern	Frequency	Description
uniphasic	80–95%	symptoms peak and resolve within hours
biphasic	~5%	symptoms recur 1–48 h after complete resolution, without re-exposure
protracted	rare	symptoms persist >4 h
refractory	rare	persistent despite ≥3 doses epinephrine + supportive management

tryptase

• specific serum marker for mast cell activation — supports but does not diagnose anaphylaxis
• draw within 15 min–3 h of reaction onset
• can be normal in food-induced anaphylaxis or if normotensive
• results may take weeks to return

mechanisms

Pathway	Trigger examples
IgE-mediated (most common)	foods, venoms, latex, drugs
IgG / immune complex	infusions, blood products
complement-mediated (C3a/C5a)	dialysis membranes, protamine
non-immunologic — direct mast cell	opioids, vancomycin, radiocontrast
physical	exercise, cold, heat
idiopathic	no identifiable trigger
cofactor-dependent	exercise + food/NSAIDs/alcohol
mastocytosis / mast cell activation disorder	multiple mechanisms

management

step 1: immediate actions

• ABCs, IV access, O₂, monitors
• remove trigger if ongoing (stop IV drug infusion)
• lie patient supine (left lateral decubitus if pregnant → reduce aortocaval compression)
• do not sit patients up unless in respiratory extremis

step 2: epinephrine

IM (first-line):

• 0.5 mg IM (0.01 mg/kg up to 0.5 mg) of 1 mg/mL (1:1,000) solution
• inject into anterolateral thigh
• repeat every 5–15 minutes as needed

IV (second-line — perioperative/ICU or refractory):

• use 0.1 mg/mL (1:10,000) solution
• push: 0.1 mg IV over 1–10 min (impending arrest, drip not yet available)
• infusion: 0.1–0.2 mcg/kg/min, titrate q2–3 min by 4 mcg/min

Epinephrine MOA: α₁ (vasoconstriction, decreased airway oedema) + β₁ (inotropy, chronotropy) + β₂ (bronchodilation, mast cell stabilisation)

PAF timing: platelet activating factor peaks 60–90 min after onset → epinephrine is less effective after PAF stimulation → early administration is critical

step 3: adjunctive therapy

• IV crystalloid bolus — especially if persistently hypotensive after epinephrine
• inhaled SABA — reasonable if ongoing expiratory wheezing, but consider whether anaphylaxis is being undertreated (may need more epinephrine instead)
• glucagon — consider if on beta-blockers and not responding to epinephrine
  • 1–5 mg slow IV bolus over 5 min, then 5–15 mcg/min infusion if needed
  • rapid infusion → vomiting (caution with unprotected airway)

step 4: escalation

• stridor, muffled voice, airway compromise → call for anaesthesia/ICU/airway service
• vitally unstable after 1–2 doses of epinephrine + IV fluids → activate code/ICU

monitoring and disposition

biphasic reaction risk factors

• unknown trigger
• severe initial reaction
• required >1 dose of epinephrine
• cutaneous manifestations
• wide pulse pressure
• delay in initial epinephrine administration (the only modifiable factor)

observation duration

Risk level	Minimum observation
lower risk, symptoms fully resolved	≥1 hour asymptomatic
severe reaction, >1 dose epi, unknown trigger, poor baseline cardiorespiratory reserve	≥6 hours (consider admission)

• all patients observed until complete resolution of signs and symptoms

what NOT to do

• not recognising anaphylaxis — urticaria/angioedema are not required
• not giving epinephrine at all — the most common fatal error
• delaying epinephrine — waiting for full diagnostic criteria or trying antihistamines first
• IV epinephrine when IM would suffice — higher risk, more complications
• prioritising antihistamines or steroids over epinephrine — no evidence these prevent biphasic reactions or improve outcomes
• confusing vasovagal syncope with anaphylaxis — vasovagal = bradycardia; anaphylaxis = tachycardia

differential diagnosis

Category	Mimics
common	vasovagal syncope (bradycardia, rapid recovery), acute spontaneous urticaria/angioedema, acute asthma
cardiovascular	MI, PE, other shock (hypovolaemic, cardiogenic, septic, obstructive)
flushing disorders	carcinoid, phaeochromocytoma, VIPoma
postprandial	scombroid poisoning, pollen-food allergy syndrome, food poisoning
angioedema (non-anaphylactic)	hereditary angioedema, ACE inhibitor–induced, DPP-IV inhibitor–induced
drug reactions	vancomycin infusion reaction (red man syndrome)
non-organic	vocal cord dysfunction, hyperventilation, panic attack (can trigger stress-induced urticaria), factitious disorder
mast cell disease	mastocytosis (can also cause anaphylaxis)

disposition and follow-up

• refer to allergist as outpatient
• epinephrine autoinjector prescription:
  • yes → food allergy, venom allergy, idiopathic anaphylaxis
  • probably not needed → drug allergy (avoidance is primary strategy)