Anaphylaxis

Question 1

Anaphylaxis - define

Answer 1

Anaphylaxis is a serious systemic hypersensitivity (allergic) reaction that is rapid in onset and may cause death.

Question 2

The mortality associated with anaphylaxis is less than …% in patients presenting to hospital.

Answer 2

The mortality associated with anaphylaxis is less than 1% in patients presenting to hospital.

Question 3

The overall risk of recurrent anaphylaxis is estimated at 1 in … per year within the UK.

Answer 3

The overall risk of recurrent anaphylaxis is estimated at 1 in 12 per year within the UK.

Question 4

A specific trigger is commonly identified in anaphylaxis but up to …% of cases may be idiopathic (i.e. no known cause). The most commonly recognised allergens include food, drugs and venom (e.g. insect bites or stings).

Answer 4

A specific trigger is commonly identified in anaphylaxis but up to 30% of cases may be idiopathic (i.e. no known cause). The most commonly recognised allergens include food, drugs and venom (e.g. insect bites or stings).

Question 5

Aetiology of anaphylaxis - broad range of allergens

Answer 5

Food (most common in young people): common examples include peanuts, walnuts, shellfish, Cow’s milk, eggs
Drugs: common examples include antibiotics, neuromuscular blocking agents, NSAIDs, Chlorhexidine
Venom: stinging insects (e.g. honeybees, fire ants, yellow jackets) and biting insects (less common)
Occupational: latex
Food additives

Question 6

In non-immunological mechanisms there is direct activation of mast cells and basophils leading to release of chemical mediators such as histamine. Examples include:

Answer 6

Physical factors: exercise, cold, heat. Exercise is often associated with a cofactor (e.g. food or drug)
Radiological contrast agents
Medications: NSAIDs, codeine, vancomycin. NSAIDs may cause both non-immunological and IgE-mediated reactions.

Question 7

The predominant mechanism of anaphylaxis is exposure to an allergen leading to …-mediated activation of mast cells and ….

Answer 7

The predominant mechanism of anaphylaxis is exposure to an allergen leading to IgE-mediated activation of mast cells and basophils.

Question 8

IgE is one of five types of antibody in the body. IgE, like all antibodies, are produced by B cells. IgE is normally involved in defence against parasitic disease, but is also central to the pathophysiology of ‘allergic’ disease. Allergy refers to an … immune response to an otherwise … substance (e.g. pollen/nuts).

Answer 8

IgE is one of five types of antibody in the body. IgE, like all antibodies, are produced by B cells. IgE is normally involved in defence against parasitic disease, but is also central to the pathophysiology of ‘allergic’ disease. Allergy refers to an exaggerated immune response to an otherwise innocuous substance (e.g. pollen/nuts).

Question 9

Sensitisation - allergies

Answer 9

In development of an allergic response there is an initial process called sensitisation. After entry of an allergen into the body, it is taken up by antigen-presenting cells that interact with T-helper type 2 (Th2) cells that signal for stimulation of B-cells within lymphoid tissue. This leads to allergen-specific IgE production by B cells. The released IgE then binds to mast cells and some basophils located around the body, particularly in the skin, gut and lungs.

Question 10

Re-exposure following sensitisation - allergies

Answer 10

Following sensitisation, patients may develop an allergic-reaction on re-exposure. If the patient is re-exposed to the same allergen and it diffuses in the proximity of these mast cells it can lead to binding on the IgE antibodies. Binding leads to cross-linking and aggregation that initiates intra-cellular signalling. If this signal is strong enough, it leads to activation and degranulation causing release of massive amounts of chemical mediators including histamine, tryptase, cytokines, prostaglandin and leukotrienes.

These chemical mediators act directly on tissue as well as recruit additional inflammatory cells (e.g. eosinophils). They cause local inflammation, vessel dilatation, loss of vascular integrity and fluid extravasation leading to oedema. The combination of oedema and massive vasodilatation can lead to airway obstruction, bronchoconstriction and reduced cardiac output. This culminates in marked hypoxia and hypotension that leads to anaphylactic shock.

Question 11

… is characterised by sudden onset airway and/or breathing and/or circulatory dysfunction often with typical skin/mucosal changes.

Answer 11

Anaphylaxis is characterised by sudden onset airway and/or breathing and/or circulatory dysfunction often with typical skin/mucosal changes.

Question 12

‘Airway’ clinical features in anaphylaxis (A-E) - 3

Answer 12

Throat/tongue swelling
Horse voice
Stridor

Question 13

‘Breathing’ clinical features anaphylaxis (A-E) - 5

Answer 13

Dyspnoea
Wheeze
Hypoxia
Persistent cough
Respiratory arrest

Question 14

‘Circulation’ clinical features in anaphylaxis (A-E) - 5

Answer 14

Pale, clammy
Dizziness
Tachycardia
Hypotension
Cardiac arrest

Question 15

‘Disability’ clinical features in anaphylaxis (A-E) - 4

Answer 15

Assessment of conscious level is vital. Decreased brain perfusion may reduce conscious level and compound airway obstruction. Features may include:

Reduced Glasgow coma score (GCS)
Agitation
Confusion
‘Feeling of impending doom’

Question 16

‘Exposure’ clinical features in anaphylaxis (A-E) - 2

Answer 16

Cutaneous findings are often the first feature of anaphylaxis, but may be absent in 10-20% of cases. Signs may be subtle (e.g. patchy erythema only). The two classic signs are urticaria and angio-oedema:

Urticaria: red, itchy, raised papules or plaques
Angio-oedema: swelling affecting deeper tissue. Commonly seen in lips, mouth and/or face

Question 17

Basic investigations - A-E anaphylaxis

Answer 17

A series of basic investigations should be requested including urgent bloods (e.g. full blood count, urea & electrolytes), arterial or venous blood gas, 12-lead ECG and chest x-ray. These investigations are not specific to anaphylaxis, instead they represent a routine set of investigations for any critically unwell patient.

Other investigations may be warranted depending on the suspected trigger or co-morbidities of the patient.

Question 18

… cell tryptase is one of the major proteins released during activation and degranulation. This means its concentration will increase during an episode of anaphylaxis. Therefore, mast cell tryptase can be used as a surrogate marker of anaphylaxis and analysis of this protein is used in the follow-up of anaphylaxis. Importantly, it is NOT useful in the initial recognition and management of anaphylaxis.

Answer 18

Mast cell tryptase is one of the major proteins released during activation and degranulation. This means its concentration will increase during an episode of anaphylaxis. Therefore, mast cell tryptase can be used as a surrogate marker of anaphylaxis and analysis of this protein is used in the follow-up of anaphylaxis. Importantly, it is NOT useful in the initial recognition and management of anaphylaxis.

Question 19

The principal pharmacological treatment of anaphylaxis is intramuscular …

Answer 19

The principal pharmacological treatment of anaphylaxis is intramuscular adrenaline.

Question 20

The emergency management of anaphylaxis should be in line with the Resuscitation council 2021 guidelines. In a patient with suspected anaphylaxis the following algorithm should be followed:

Answer 20

Question 21

Adrenaline is the principal medication used to treat anaphylaxis. It is given as an intramuscular (IM) injection (even if the intravenous route is available) into the anterolateral aspect of the anterior thigh. The concentration of adrenaline should be 1:… that is equivalent to 1mg/ml. The dose depends on the age of the patient:

Answer 21

Adrenaline is the principal medication used to treat anaphylaxis. It is given as an intramuscular (IM) injection (even if the intravenous route is available) into the anterolateral aspect of the anterior thigh. The concentration of adrenaline should be 1:1000 that is equivalent to 1mg/ml. The dose depends on the age of the patient:

Adult and child >12 years old: 500 micrograms IM (0.5 mL of 1mg/mL adrenaline)
6-12 years old: 300 micrograms IM (0.3 mL of 1mg/mL adrenaline)
6 months - 6 years: 150 micrograms IM (0.15 mL of 1mg/mL adrenaline)
< 6 months: 100-150 micrograms IM (0.1-0.15 mL of 1mg/mL adrenaline)

Question 22

Adult and child >12 years old: … micrograms IM adrenaline

Answer 22

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

Question 23

Adrenaline treats anaphylaxis by its action on two receptors:

Answer 23

Alpha-adrenergic receptors: causes vasoconstriction that reverses peripheral vasodilation and reduces tissue oedema
Beta-adrenergic receptors: causes bronchodilation, increases myocardial contractility and suppresses histamine/leukotriene release. Also inhibits mast cell activation

Question 24

A second dose of adrenaline may be given after …

Answer 24

A second dose of adrenaline may be given after 5 minutes if there is no improvement. If there is no improvement after two doses of adrenaline treatment should follow the refractory anaphylaxis algorithm in line with the resuscitation council guidance.

Question 25

Anti-histamines in anaphylaxis ?

Answer 25

The use of anti-histamines was traditionally part of the initial management of anaphylaxis. However, they are currently NOT recommended as part of the initial management. They can be used to treat skin symptoms (e.g. urticaria/angio-oedema) that occur alongside anaphylaxis but use should not delay administration of adrenaline and IV fluids.

A second-generation non-sedating agent (e.g. cetirizine) should be given via the oral route. If the oral route is not available, chlorphenamine may be given intravenously or intramuscularly. This is a first-generation sedating anti-histamine.

Question 26

The use of corticosteroids (e.g. intravenous hydrocortisone) was traditionally part of the initial management of anaphylaxis. Is it still advised?

Answer 26

The use of corticosteroids (e.g. intravenous hydrocortisone) was traditionally part of the initial management of anaphylaxis. The primary use was to prevent the late phase inflammatory response (i.e. biphasic reaction). However, there is little evidence they shorten protracted symptoms. Therefore, the routine use of steroids is no longer advised.

Corticosteroids may be considered for refractory reactions or ongoing asthma/shock after the initial resuscitation. Importantly, they should not be given in preference to adrenaline.

Question 27

Patients with evidence of hypotension/shock or those that have a poor initial response to adrenaline should be given an intravenous fluid bolus. The initial bolus should be:

Answer 27

Adults: 500-1000 mL of non-glucose-containing crystalloid (e.g. 0.9% sodium chloride, Hartmann’s)
Children: 10 mL/kg of non-glucose-containing crystalloid (e.g. 0.9% sodium chloride, Hartmann’s)

Question 28

Refractory anaphylaxis - define

Answer 28

Defined as anaphylaxis requiring ongoing treatment despite two appropriate doses of adrenaline.

Question 29

Refractory anaphylaxis

Answer 29

The exact mechanism of refractory anaphylaxis is poorly understood. However, it is likely due to a combination of delayed administration of adrenaline, ongoing release of inflammatory mediators or diminished response to adrenaline.

Patient with refractory anaphylaxis should be referred to the critical care team for ongoing support. The principal treatment is initiation of an adrenaline infusion. Repeated doses of intramuscular adrenaline should be given at 5 minute intervals whilst the intravenous infusion is being prepared and ongoing fluid resuscitation should be administered.

For more information, see the refractory anaphylaxis algorithm published by the resuscitation council.

Question 30

Biphasic reaction refers to …

Answer 30

This refers to the recurrence of symptoms several hours later in the absence of exposure to the allergen.

Question 31

The biphasic reaction is estimated to occur in around 5% of patients with anaphylaxis. The median time to developing a biphasic reaction is … hours. It can be difficult to distinguish this reaction from sustained anaphylaxis that had a transient response to adrenaline or further absorption of the allergen in the gastrointestinal tract (food allergies).

Answer 31

The biphasic reaction is estimated to occur in around 5% of patients with anaphylaxis. The median time to developing a biphasic reaction is 12 hours. It can be difficult to distinguish this reaction from sustained anaphylaxis that had a transient response to adrenaline or further absorption of the allergen in the gastrointestinal tract (food allergies).

Question 32

The biphasic reaction is estimated to occur in around ..% of patients with anaphylaxis. The median time to developing a biphasic reaction is 12 hours. It can be difficult to distinguish this reaction from sustained anaphylaxis that had a transient response to adrenaline or further absorption of the allergen in the gastrointestinal tract (food allergies).

Answer 32

The biphasic reaction is estimated to occur in around 5% of patients with anaphylaxis. The median time to developing a biphasic reaction is 12 hours. It can be difficult to distinguish this reaction from sustained anaphylaxis that had a transient response to adrenaline or further absorption of the allergen in the gastrointestinal tract (food allergies).

Question 33

Risk factors for developing a biphasic reaction include:

Answer 33

Severe initial presentation
More than one dose of adrenaline required
Delay in giving adrenaline (>30-60 minutes from initial symptoms)

Question 34

Due to the risk of a biphasic reaction patients are traditionally observed for a period of 6-12 hours, however, fatal outcomes are very rare. More recently, depending on a patients risk of developing a biphasic reaction, observation may be for a shorter period of time.

Deemed at low risk: minimum .. hours observation from resolution
Deemed at moderate risk: minimum of … hours observation from resolution
Deemed high risk: minimum of … hours observation from resolution

Answer 34

Deemed at low risk: minimum 2 hours observation from resolution
Deemed at moderate risk: minimum of 6 hours observation from resolution
Deemed high risk: minimum of 12 hours observation from resolution

Question 35

Follow-up management in anaphylaxis

Answer 35

Information on discharge and follow-up in an allergy clinic are important following anaphylaxis.

Question 36

Discharge information

Several broad principles are required prior to discharging a patient following an anaphylactic reaction (list 4)

Answer 36

Review by a senior clinician: helps to determine whether further observation is warranted and patient is safe to go home
Patient information on anaphylaxis: should discuss clinical features of anaphylaxis, the biphasic reaction and what to do if they occur. Also need to give advice on avoiding triggers (if possible) and provide information about support groups
Prescriptions: patients should be prescribed a new or replacement adrenaline auto-injector (except in drug induced reactions unless it would be difficult to avoid the drug). There are various brands (e.g. Epipen®) and patients should be trained how to use them. Usually come as dose of 300 mcg (adults) or 150 mcg (children). Patients should have two devices at all times
Referral: patients should be referred to an allergy/immunology clinic on discharge

Question 37

Allergy clinic referral - anaphylaxis

Answer 37

All patients should be referred to an allergic clinic on discharge. Each patient will be reviewed by a clinical immunologist or allergist to determine whether the reaction was true anaphylaxis and the likely underlying cause. This should be conducted in an outpatient clinic once the patient is stable and discharged from hospital

Numerous test can be requested including mast cell tryptase to compare with the level at the time of the reaction, allergen-specific IgE antibodies and skin-prick testing.

Question 38

Allergen specific IgE antibodies:

Answer 38

Allergen specific IgE antibodies: this describes performing assays for IgE specific to an allergen to help diagnose allergic disease. This is an in vitro blood test that has no risk to the patient and is generally not affected by medications. A positive test means the patient is sensitised to the allergen and may have a clinical reaction to it. However, sensitisation alone is not enough to diagnose an allergy because not all patients will develop symptoms on re-exposure

Question 39

Skin testing: this describes …

Answer 39

Skin testing: this describes a rapid, sensitive and cost-effective in vivo test. Allergens are introduced into the skin by a ‘skin prick’. The allergens comes into contact with cutaneous mast cells that leads to a transient urticarial reaction if the patient is ‘allergic’. It cannot be performed in patients at high risk of anaphylaxis on re-exposure

Question 40

Complications of anaphylaxis

Answer 40

Anaphylaxis is a life-threatening condition that can lead to death without urgent treatment.
Without treatment, anaphylaxis can be fatal but thankfully the mortality is estimated as <1% in patients presenting to hospital. Approximately 50% of deaths are due to circulatory collapse (shock) and 50% due to respiratory arrest.

Allergic reaction secondary to food are more likely to lead to respiratory arrest. Insect stings/bites and medications are more likely to lead to circulatory collapse.