Pathophysiology and causation in Anaphylaxis

Pathophysiology and causation

Definition

Anaphylaxis is defined as a severe reaction of sudden onset that has the potential to be fatal (Arnold and Williams 2011, NICE 2011).

Most episodes of this systemic response to a specific allergen will occur within one hour of exposure (Arnold and Williams 2011), although in a minority of cases response may occur as quickly as within three minutes or as long as within six hours depending on the route of exposure and nature of the allergen (RCUK 2008, Lockey and McCann 2012).

Response may be quicker if exposure involves ingestion of certain food products associated with an increased risk of an anaphylactic reaction, such as nuts or shellfish, insect stings or bites, or intravenous administration of medication. Conversely, secondary to a slower rate of absorption, response may be delayed when medication is administered or mammalian food, such as certain meat products, is ingested (Figure 1) (RCUK 2008, Mustafa 2012).

Figure 1

Precipitants of anaphylaxis

Food-related reactions are most prevalent among young children, while medication causes the majority of anaphylactic reactions in those over 55 years (Reading 2009, Arnold and Williams 2011, NICE 2011). The most common precipitants of anaphylaxis are (Tupper and Visser 2010, Mustafa 2012):

• Foods such as dairy products, nuts and shellfish.
• Certain medications such as antibiotics and non-steroidal anti-inflammatory drugs.
• Venomous bites and stings.
• Intravenously administered contrast materials used in medical investigations.
• Latex.

An Australian study found venomous stings and bites accounted for 30% of cases of anaphylaxis, food products were associated with 18%, iatrogenic causes accounted for 22% of cases, idiopathic causes for 25%, with other rarer causes comprising the remaining 5% of anaphylactic reactions (Brown 2006). These figures probably over-represent the proportion of episodes attributable to venomous stings and bites as these are more prevalent in tropical areas, and medication exposure may account for a greater proportion of episodes in the UK (Mustafa 2012).

Overall rates of anaphylaxis do not appear to differ significantly between countries, with rates varying between 0.05% and 2% of the total population (González-Pérez et al 2010, Dunbar and Luyt 2011, Mustafa 2012, Caton and Flynn 2013). Latex-associated anaphylaxis peaked globally during the 1980s, probably because of universal precautions taken during the early recognition of human immunodeficiency virus (HIV) syndrome, however incidence has declined with the increased use of latex-free products in health care (Reading 2009).

The paucity and acknowledged inaccuracy of data make accurate analysis of causative factors challenging (House of Lords Science and Technology Committee 2007, Sheikh et al 2008). However, it is estimated that food allergy affects approximately 6% of those under three years in the UK (Department of Health (DH) 2006) and 6-8% of all children in the United States (US), and that food-induced anaphylaxis is the most common anaphylaxis treated in US hospitals (Shah and Pongracic 2008).

The most common food products associated with anaphylactic reactions are:

• Tree nuts.
• Peanuts.
• Fish.
• Shellfish.
• Milk.
• Eggs.
• Kiwi fruit.

Almost any food may be implicated (Brown 2006, Shah and Pongracic 2008, Arnold and Williams 2011, Dunbar and Luyt 2011). There has been a particularly marked rise in the incidence of peanut allergy over the past 20 years, with a 120% rise in incidence noted in the UK between 2001 and 2005 (Information Centre for Health and Social Care 2007). Peanut allergy is the most common life-threatening food allergy, with more than 250,000 children in the UK thought to experience allergic or anaphylactic reactions to peanuts or other nuts (House of Commons Health Committee 2004, Reading 2009).

Complete time out activity 1

What advice should healthcare professionals give to parents of young children who may have anaphylactic reactions to certain foods?

Once completed your time out activity is saved and stored in "My Modules”.

Anaphylaxis should be graded as immune, non-immune or idiopathic in nature (Brown 2006). Since the clinical manifestations and emergency treatment do not differ, the necessity to identify immunologically driven anaphylaxis from non-immune and idiopathic reactions is not necessary during the initial management of the reaction.

Pathophysiology of anaphylaxis that is immune in nature

• Anaphylaxis can be characterised as an immunologically driven response to an allergen.
• The allergen will prompt an antibody response that leads to the activation of mast cells and basophils, causing release of histamine, platelet-activating factor and heparin, among other chemicals (Ben-Shoshan and Clarke 2011).
• At its most severe, this causes widespread vasodilation and tissue permeability in conjunction with tissue swelling.
• Widespread tissue permeability may lead to sequestering of fluid from the intravascular to the extravascular space, and patients may present with clinical shock and associated acute respiratory distress secondary to soft tissue swelling in the upper and lower respiratory tract (Bryant 2007, Arnold and Williams 2011).
• The immunoglobulin most commonly associated with this allergen-provoked reaction is immunoglobulin E (IgE) (Arnold and Williams 2011).

Pathophysiology of anaphylaxis that is non-immune in nature

• Anaphylaxis that is not immunologically driven has been termed non-immune, and results from direct provocation of mast cells rather than as an antibody-driven response.
• These reactions might include those encountered during the administration of contrast media in radiology departments, for example (Carchietti and Cecchi 2009, Arnold and Williams 2011).
• In some instances, anaphylaxis is idiopathic in nature; that is, there is no established cause for it, and idiopathic episodes may account for up to 20% of all cases (Tupper and Visser 2010, NICE 2011).
• Other rare causes of the reaction include heat, cold, sunlight and exercise (Arnold and Williams 2011).

Complete time out activity 2

Consider the implications of potential non-immune reactions for medical and nursing staff working in radiology departments. What should staff be particularly aware of, how should they care for patients receiving contrast media, and what resources will they need to maintain patient safety?

Once completed your time out activity is saved and stored in "My Modules”.

Learning points

1. Anaphylaxis is an increasingly common and potentially life-threatening allergic reaction accounting for approximately 20 deaths a year in the UK, with up to 50% of these deaths being iatrogenic.
2. Anaphylaxis is defined as a severe reaction of sudden onset that has the potential to be fatal. Most episodes of this systemic response to a specific allergen will occur within one hour of exposure, although in a minority of cases response may occur as quickly as within three minutes or as long as within six hours depending on the route of exposure and nature of the allergen.
3. The most common precipitants of anaphylaxis are foods such as dairy products, nuts and shellfish, certain medications such as antibiotics and non-steroidal anti-inflammatory drugs, venomous bites and stings, intravenously administered contrast materials used in medical investigations, and latex.
4. The most common food products associated with anaphylactic reactions are tree nuts, peanuts, fish, shellfish, milk, eggs and kiwi fruit, although almost any food may be implicated.
5. Peanut allergy is the most common life-threatening food allergy, with more than 250,000 children in the UK thought to experience allergic or anaphylactic reactions to peanuts or other nuts.
6. Anaphylaxis can be characterised as an immunologically driven response to an allergen. The allergen will prompt an antibody response that leads to the activation of mast cells and basophils, causing release of histamine, platelet-activating factor and heparin. The immunoglobulin most commonly associated with this allergen-provoked reaction is immunoglobulin E (IgE).