Anaphylaxis

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction, which is characterised by rapidly developing and life threatening problems with the airway, breathing and/or circulation, usually associated with skin and mucosal changes. However, the latter may be absent in up to 20% of cases.¹

It usually has a rapid onset with multiple organ involvement and is mostly caused by specific antigens in sensitised individuals.

The range of possible presentations can make diagnosis difficult but medical treatment must be started as soon as possible.

A significant number of cases of anaphylaxis are idiopathic.¹

Incidence of Anaphylaxis

1 in 300 people will experience anaphylaxis at some point in their lives however the overall prognosis of anaphylaxis is good, with a case fatality rate of under 1% in those presenting to hospitals in the UK.

Each year in the UK there are 2030 reported deaths due to anaphylaxis in the UK with approximately 10 from food triggers and 10 from peri-operative anaesthesia.²

Signs and Symptoms of Anaphylaxis

Overall prognosis is good if treatment is started promptly, with a fatality rate of <1%. The typical signs and symptoms of anaphylaxis are shown below.

Airway problems: lip and tongue swelling/angioedema, nasal congestion, sneezing, tightness of throat/hoarse voice/stridor.

 

Breathing problems: tachypnoea, bronchospasm/wheeze, increased mucous secretions, exhaustion due to increased work of breathing, confusion due to hypoxia, cyanosis, respiratory arrest.

Circulation problems: hypotension, tachycardia, arrhythmia, myocardial ischemia, cardiac arrest, signs of shock.

Neurological problems: confusion, agitation, loss of consciousness

Skin and mucosal problems: urticaria, erythema, pruritus

Gastrointestinal problems: stomach cramps, nausea, vomiting, diarrhoea

Psychological problems: A feeling of impending doom

 

Common agents known to cause anaphylaxis include:

• Antibiotics, especially penicillin (the most common cause of drug induced anaphylaxis), aspirin and NSAIDs (second most common cause of drug induced anaphylaxis).
• Angiotensin Converting Enzyme Inhibitors
• Food, e.g. peanuts, egg and seafood (food is the most common cause of anaphylaxis in children) The clinical cross-reactivity with other foods in the same group is unpredictable.
• Insect stings (bees and wasps)
• Hereditary C1 esterase inhibitor deficiency (usually inhibited as an autosomal dominant, but also occurs with lymphoma and certain connective tissue disorders)
• Idiopathic

 

Less commonly:

• Physical triggers, e.g. exercise, cold
• Biological fluids, e.g. transfusions, semen
• Latex

 

Anaphylaxis is likely when all three of the following criteria are met:

• Acute onset of illness and sudden progression
• Skin and/ or mucosal changes, e.g. flushing, urticaria, angioedema
• Life threatening Airway and/ or Breathing and/ or Circulation problems

Skin or mucosal changes alone are not a sign of an anaphylactic reaction.

Skin or mucosal changes can be subtle or absent in up to 20% of reactions, e.g. some patients can have only a decrease in blood pressure, i.e. a circulation problem.

 

Anaphylaxis requires:

1. Acute onset of illness with a sudden progression
2. Skin or mucosal changes
3. Life threatening ABC problems

 

Allergic Response

Allergic anaphylaxis is an example of immediate type 1 hypersensitivity. The patient becomes sensitised to an allergen. On a further exposure to that allergen, the responsible allergenic antigen binds to an antigen-specific IgE antibody, leading to mast cell degranulation. The response is caused by the binding of an antigen to an antigen-specific antibody leading to mast cell degranulation. Histamine and other mediators, including leukotrienes, tumour necrosis factor and various cytokines, are released from mast cells and basophils following exposure to this antigen. This causes:

• Increased bronchial smooth muscle tone causing wheeze and shortness of breath
• Decreased vascular tone
• Increased capillary permeability leading to hypotension and an urticarial rash

 

The response is usually uniphasic, reported biphasic response varies from 1-20%.

Life-threatening conditions

• asthma (can present with similar symptoms and signs to anaphylaxis, particularly in children)
• Septic shock (hypotension with petechial/purpuric rash).

Non-life-threatening conditions

• Vasovagal episode
• Panic attack or hyperventilation syndrome
• Breath holding episode in a child
• Systemic mast cell disorders
• Idiopathic (non-allergic) urticaria or angioedema.

 

Mast Cell Tryptase

Mast cell tryptase is released during the anaphylactic reaction and may be measured in the blood.

It reaches its peak blood concentration approximately 1-2 hours after the reaction. This is useful to aid later diagnosis and treatment and can help in the diagnosis in uncertain cases.

The half-life of tryptase is short (approximately 2 hours) and concentrations may be back to normal within 6-8 hours, so timing of any blood samples is very important.

Measurement of mast cell tryptase is recommended in all patients with suspected anaphylaxis when the diagnosis remains uncertain.¹

The Resuscitation Council recommend that three tryptase levels are taken:

• As soon as resuscitation has started
• 1-2 hours after symptoms have started
• 24 hours later or in convalescence (some people have raised baseline tryptase levels)

Current NICE guidelines recommend all adults and young people over 16yrs who present with a suspected anaphylactic reaction should have a sample taken as soon as possible after emergency treatment has started, and a second sample ideally within 1-2 hours (but no later than 4 hours) from the onset of symptoms.

Testing should be considered in all children under 16yrs who present with suspected venom-related, drug-related or idiopathic anaphylaxis only.

Emergency Treatment – Overview

Key steps in the emergency treatment of anaphylaxis are:

• Initial steps
  • Call for help, lie the patient flat and raise the patients legs
  • Establish an airway if necessary and apply high flow oxygen
  • Apply appropriate monitoring (blood pressure, pulse oximetry, ECG)
  • Remove the trigger if possible
• Adrenaline
  • Give immediately or as soon as it becomes available
  • See next slide for further details.
• Fluid challenge
  • Give a crystalloid fluid bolus
  • Adults: 500-1000ml intravenously
  • Children: 20ml/kg intravenously

Adrenaline

Adrenaline is the most important drug in the treatment of anaphylaxis and there is no absolute contraindication for its administration in treating this condition.

When to administer adrenaline

Adrenaline may be administered in life-threatening anaphylactic reactions, even when the following relative contraindications are present:

• Coronary artery disease
• Uncontrolled hypertension
• Serious ventricular arrhythmias
• The second stage of labour

 

What affect does it have?

Adrenalines alpha-adrenoceptor actions reverse the peripheral vasodilatation and reduce oedema. It also has a beta-receptor action that causes airway dilation, increases the force of myocardial contraction and suppresses the histamine and leukotriene release.

 

How much to give?

Adrenaline IM dose Use 1 mg/mL [1:1000] adrenaline

Adult and child* > 12 years: 500 micrograms IM (0.5 mL of 1 mg/ml adrenaline)

6 12 years: 300 micrograms IM (0.3 mL)

6 months 6 years: 150 micrograms IM (0.15 mL)

< 6 months: 100 150 micrograms IM (0.1 to 0.15 mL)

*Give 300 micrograms IM (0.3 mL) in a child who is small or prepubertal

Very important! These are very small volumes. They are NOT to be given intravenously, and are NOT the adrenaline concentrations used in cardiac arrest (which is 1:10,000)

Warning: Rapid intravenous infusions of adrenaline may cause death from cerebrovascular haemorrhage, or cardiac arrhythmias or infarction.

 

• Repeat the IM adrenaline dose after 5 minutes if there is no improvement in the patients condition.
• Nebulised adrenaline can be a useful adjunct in managing upper airway obstruction due to laryngeal oedema, but it should only be considered after intramuscular (or intravenous) adrenaline has been administeredbut not as a substitute. Recommended doses are 5 mL of 1 mg/mL (1:1 000) adrenaline
• IV adrenaline should only be given by experienced specialists in an appropriate setting.

Emergency Treatment Other

There is no role for anti-histamine use in the immediate treatment of anaphylaxis. After the patient has been stabilised, a non-sedating anti-histamine can be given to help alleviate cutaneous symptoms.

The routine use of corticosteroids to treat anaphylaxis is not advised. If the patient is suffering from ongoing asthma/shock after initial resuscitation steroids may be considered, however must not be given preferentially to adrenaline. There is little evidence that steroids shorten symptoms or prevent biphasic reactions.¹

Consider inhaled bronchodilator therapy with salbutamol and/or ipratropium for the persisting respiratory symptoms.

Further Treatment

C1 esterase inhibitor

Non-histaminergic angioedema such as ACE-induced angioedema and hereditary angioedema can present very similarly to anaphylaxis. Hereditary angioedema caused by C1 esterase inhibitor deficiency is resistant to steroids, antihistamines and adrenaline.

Anaphylaxis due to C1 esterase inhibitor deficiency is resistant to adrenaline, steroids and antihistamines and needs treatment with C1 esterase inhibitor concentrate or fresh frozen plasma.

Glucagon

Patients who are taking beta blockers may be resistant to the therapeutic effects of adrenaline. Animal studies and case reports suggest that glucagon can be successfully used to overcome the beta blockade, if initial adrenaline doses are unsuccessful.

Learning bite

Glucagon can be helpful in patients with anaphylaxis who are taking beta blockers.

 

Further Management

Patients who have required two doses of IM adrenaline or a previous biphasic reaction will need to be observed for a minimum of 6 hours after their symptoms have resolved.

If the patient has required more than two doses of adrenaline, has severe asthma or their reaction has involved severe respiratory compromise, or they may continue to absorb the allergen (e.g. slow release medicaitons), then they will require a minimum of 12 hours observation after resolution of symptoms. This is also the case for presentations at night or where access to emergency care is difficult.

NICE recommends³ that prior to discharge, a healthcare professional with the appropriate skills and competencies should offer patients (or their parent/carer) the following:

• information about anaphylaxis, including the signs and symptoms of anaphylaxis
• information about the risk of a biphasic reaction (and clear instructions to return to hospital if symptoms return)
• information on what to do if anaphylaxis occurs
• prescription of adrenaline auto-injectors and demonstration of the correct use of the adrenaline injector and when to use it
• advice about how to avoid the suspected trigger
• information about the need for referral to a specialist allergy service and the referral process
• information about patient support groups

Patients should be provided with an emergency management or action plan.

Adrenaline auto-injector

• A prescription for two should be given rather than a single auto-injector
• Patients should be advised to have the auto-injector easily available at all times (including for example in school, on holidays or when away from home).
• Three types are commercially available (EpiPen , Jext and Emerade ).
• They come in 0.3ml and 0.15ml strengths (EpiPen and Jext ) and 0.5ml, 0.3ml and 0.15ml strengths (Emerade ) with varying shelf-lives, prices and needle lengths.

You should be comfortable with demonstrating the brand approved in your local area.

1. Resuscitation Council UK. Emergency Treatment of Anaphylactic Reactions. Guidelines for healthcare providers. 2021.
2. Pumphrey RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp 2004; 257: 116-128; discussion 128-132, 157-160, 276-285.
3. National Institute for Health and Care Excellence (NICE). Anaphylaxis: assessment and referral after emergency treatment. [CG134] 2011. Last updated: 24 August 2020
4. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000; 30(8): 1144-1150.
5. National Institute for Health and Care Excellence (NICE). Anaphylaxis. [QS119] 2016. Last updated: 31 July 2024.
6. National Institute for Health and Care Excellence (NICE). Angio-oedema and anaphylaxis: Scenario: Anaphylaxis with or without angio-oedema. NICE CKS. Last revised in August 2024.