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Acute Anaphylaxis

Key facts:

Authors: Alice Verran and Ann Anthony
Top Tip: Treat before you investigate. Use IV adrenaline with caution


Key Differential Diagnoses

  • Asthma
  • All causes of collapse
  • All causes of hypotension

Key Investigations

  • ABG
  • U+E, LFT, Bone, Glucose, Tryptase (within 6h)
    CXR, ECG

Key Treatment

  • Assess ABC rapidly (?ITU) + IVI
  • IM ADRENALINE (1:1000) 0.5 ml (500 mcg); or IV (1:10,000) 0.5 ml (50 mcg) if severely ill, peri-arrest or pulseless; ie the dose is different
  • NEB SALBUTAMOL 5mg (if wheezy)

Key Management Decisions

  • Intubate and ventilate
  • ITU


Acute onset and rapid progression are characteristic of anaphylaxis. Hypotension and airway obstruction are ominous signs



  • Anaphylaxis is an acute, life-threatening, usually IgE-mediated allergic reaction that occurs in previously sensitised people, when they are reexposed to the sensitising antigen.
  • Diagnosis is clinical
  • Acute onset and rapid progression are characteristic of anaphylaxis
  • Recurrent episodes are common
  • There is often (but not always) a history of previous sensitivity to an allergen, or recent history of exposure to a new drug (eg vaccination) 
  • Initially patients usually develop skin symptoms include generalised itching, urticaria and erythema, rhinitis, conjunctivitis and angio-oedema
  • Anaphylactic reactions can vary in severity and rate of progression - they may progress rapidly (over a few minutes) 
  • Occasionally in a biphasic manner, with symptoms recurring 12-24h later
  • Rarely manifestations may be delayed by a few hours (adding to diagnostic difficulty), or persist for more than 24 hours


  • Severe, life-threatening, generalised or systemic hypersensitivity reaction


  • Anaphylaxis can occur at any age
  • In one study, the mean age was 29.3 years (range, 0.8 to 78.2 years). In another, there was an age range of 1-79 years, with a mean of 37 years
  • 1-3 episodes per 10,000 population pa
  • Lifetime prevalence: 1-2%
  • Rare cause of hospital admission (0.02%)
  • Prevalence appears to be rising
  • Anaphylaxis is probably underdiagnosed


When allergen binds to IgE-sensitised mast cells and basophils, histamine is released from their intracellular granules. Mast cells are widely distributed but are most concentrated in skin, lungs, and GI mucosa; histamine facilitates inflammation and is the primary mediator of clinical atopy. Histamine causes the following:

  • Local vasodilation (causing erythema)
  • Increased capillary permeability and edema (producing a wheal)
  • Surrounding arteriolar vasodilation mediated by neuronal reflex  mechanisms (causing flare)
  • Stimulation of sensory nerves (causing itching)
  • Smooth muscle contraction in the airways (bronchoconstriction) and in the GI tract (increasing GI motility)
  • Increased salivary and bronchial gland secretions
  • When released systemically, histamine is a potent arteriolar dilator and can cause extensive peripheral pooling of blood and hypotension; cerebral vasodilation may be a factor in vascular headache


  • IgE dependent mechanisms. Common allergens include foods (especially nuts eg peanuts, tree nuts; shellfish); venom (bee, wasp stings); drugs: beta-lactam antibiotics (penicillins and cephalosporins), vaccines, NSAIDs, muscle relaxants, radiocontrast media, heparin, iron injections; blood products, immunoglobulins; other: latex
  • IgE independent immunologic mechanisms: eg IgG mediated, T cell activation. Causes include dextran and infliximab
  • Direct mast cell activation: May be due to physical factors (exercise, cold, heat, sunlight/UV radiation), alcohol, drugs (acetylcysteine)
  • Idiopathic: unknown trigger? mastocytosis/clonal mast cell disorder?

Risk factors

  • Comorbidities: asthma (particularly if poorly controlled), atopy, COPD, psychiatric disorders (due to under recognition), cardiovascular disease, mastocytosis
  • Concurrent medications:, alcohol/antidepressants/sedatives etc impair recognition of symptoms, beta-Blockers and ACE inhibitors worsen them
  • Recent anaphylactic reaction
  • Age: children (under recognised), adolescents (risk-taking behaviour), elderly (increased mortality due to multiple medications)


  • Symptoms are acute in onset, variable and may affect:
    Skin/mucosal tissue: pruritus, generalised hives, flushing, swelling of lips, tongue, uvula/palate, larynx, nose, eyes + other areas (angio-oedema)
  • Respiratory tract: dyspnoea, wheeze, nasal congestion, rhinorrhoea, sneezing, hoarseness, cough 
  • GI: nausea, vomiting, abdominal pain, diarrhoea, incontinence
  • Cardiovascular: chest pain, palpitations, syncope, altered mental status, shock, cardiac arrest
  • CNS: sense of impending doom, throbbing headache, dizziness, confusion, tunnel vision, loss of consciousness
  • Other: metallic taste in mouth, dysphagia, dysphonia, uterine contractions

Key Questions

  • “Have you been exposure to a known allergy/trigger?"
  • “When did symptoms start, and what are you current medications?"
  • “Has this happened before?”
  • “Are you asthmatic?”


  • Pale, clammy skin, urticaria
  • Hypotension, tachycardia, bradycardia (a late sign), other dysrhythmia
  • Increased respiratory rate, wheezing/bronchospasm, stridor (laryngeal obstruction), cyanosis
  • Decreased level of consciousness


Mast cell tryptase can rule out anaphylaxis; intradermal testing can rule it in. Do not delay resuscitation to take blood samples


  • FBC, ESR, CRP,
  • ABG
  • U+E, LFT, Bone, Glucose, Tryptase (within 6h)


  • ECG. CXR

Key Investigation

  • Mast cell tryptase

Specialist investigations

  • Tryptase; timing important. Optimally measured 15mins-3 hrs after onset; within 6h; may be high
  • Histamine: optimally measure 15-60mins after onset. Special handling required
  • Allergen-specific IgE
  • Intradermal challenge testing (especially useful for drug causes)

Differential diagnoses

  • Asthma
  • All causes of collapse
  • All causes of hypotension

  • Acute generalized hives, vasovagal reaction, panic attack, aspiration of a foreign body (infants), neurologic event (seizure, stroke)

  • More rarely: postprandial syndromes (pollenfood syndrome, scombroidosis), excess endogenous histamine syndromes (mastocytosis), flush syndromes (perimenopausal flushing, carcinoid, autonomic epilepsy), capillary leak syndrome, vocal cord dysfunction syndrome


Remove bee stings. If patient is shocked, or has significant airway obstruction, treat immediately

Treatment (first line)

  • ABC (?ITU)


  • IM ADRENALINE (1:1000) 0.5 ml (500mcg); repeat at 5 minute intervals if no improvement. This route is not recommended after cardiac arrest
  • Or, IV (1:10,000) 0.5 ml (50mcg) if severely ill, peri-arrest or pulseless; ie the dose is different
  • NEB SALBUTAMOL 5mg (if wheezy)


  • High flow oxygen: >10 l/min
  • IVI + IV fluid challenge: 500 – 1000 mL. Repeat if necessary
  • Lie patient flat, elevate legs
  • Monitor cardiac and respiratory function


  • Any drug thought to be cause
  • Inform GP if drug cause possible

Treatment (second line)

  • Further bronchodilator therapy: salbutamol (nebulised or IV), ipratropium bromide (nebulised), aminophylline (IV)
  • Glucagon may be useful if patient on beta-blocker
  • (Longterm) consider prophylactic steroids for severe idiopathic cases


  • Always

Bed plan

  • Medical Admission or Observation Ward, when stable


  • ITU?

The Rest

Death is uncommon for patients who are treated appropriately


  • Side effects of adrenaline (hypertension, tachycardia, arrhythmias, MI – these may also occur due to exposure of subclinical coronary artery disease)

Risk stratification

  • Hypotension and airway obstruction are poor prognostic signs. Bradycardia is late sign


  • GP (ring)
  • Clinical immunology. Refer to regional centre


  • 1% mortality

2° Prevention
+ Health promotion

  • Educate patient about symptoms and signs of a recurrent attack, and known common triggers
  • For patients with recurrent or severe attacks, arrange
      - Skin prick or IgE testing
      - Medical alert bracelet/card/letter
      - Adrenaline autoinjecter (0.3g Epipen) for patients to carry at all times
  • 1 in 15 patients have a biphasic response with symptoms recurring 12-24 hours later - warn patients about this issue

Don't forget

  • IM and IV drug doses are different
  • Inform GP if drug cause possible
  • Timing important when testing for markers of degranulation
  • Histamine requires special handling

Red flags

  • Hypotension
  • Stridor
  • Hypoxia
  • Decreased conscious level

Synonyms: severe allergic reaction, anaphylactic shock, allergy, hypersensitivity, acute anaphylaxis guidelines, acute anaphylaxis treatment


national guidelines Emergency treatment of anaphylactic reactions. Guidelines for healthcare providers. Working Group of the Resuscitation Council (UK). January 2008

reviews The diagnosis and management of anaphylaxis practice parameter: 2010 Update. Lieberman P et al. The Journal of Allergy and Clinical Immunology. Volume 126, Issue 3 , Pages 477-480.e42, September 2010

Anaphylaxis: Recent advances in assessment and treatment. Estelle F et al. Journal of Allergy and Clinical Immunology Vol. 124, Issue 4, Pages 625-636, October 2009

World Allergy Organization anaphylaxis guidelines: Summary. Estelle F et al. The Journal of Allergy and Clinical Immunology

Anaphylaxis. Estelle F et al. Journal of Allergy and Clinical Immunology Vol. 125, Issue 2, Supplement 2, Pages S161-S181, February 2010

Anaphylaxis: diagnosis and management. Simon G A Brown, Raymond J Mullins and Michael S Gold. MJA; 185 (5): 283-289, 2006