Introduction

Acute allergic reactions resulting from the degranulation of mast cells present as a continuum of responses from mild cutaneous erythema and urticaria to severe hypotension, collapse, and death. Different authorities include varying components of this continuum in the definition of anaphylaxis.¹ Anaphylaxis may be defined as a severe acute allergic reaction that involves the respiratory tract and/or results in circulatory compromise with hypotension.

Along with the increasing incidence of allergic diseases anaphylaxis admissions to Australian, USA and UK hospitals have increased. Australian studies reported a two- to fourfold rise in anaphylaxis hospital admissions over an 11-year period from 1994.^2,3 The most dramatic rise was reported in children less than 5 years of age, with an almost 7-fold increase in hospital admissions from anaphylaxis. The increasing reactions are predominately due to foods. Despite the increase in admissions, death from anaphylaxis in childhood remains rare (the Australian mortality rate has remained stable at 1 per million population per year over an 11-year time period. ³ Thus there is a paradox that although anaphylaxis admissions are increasing, particularly in children less than 5 years of age, death from anaphylaxis remains rare, with the majority of deaths occurring in teenage or adult years rather than in early childhood.

Pathophysiology

Anaphylaxis is due to mast cell mediator release. Those mediators with vasoactive and/or bronchoconstrictive activities (histamine and the sulfidopeptide leukotrienes) are principal factors in the development of anaphylaxis. An increase in vascular permeability causes loss of fluid from the circulation into the interstitial space. The relative contributions of the mediators to the various clinical features are not completely defined. Mediators may directly compromise cardiac muscle function, and the intravascular volume depletion and haemoconcentration further compromises the cardiac output. Secondary cardiac arrhythmias can occur. Both upper and lower airways are affected. Laryngeal oedema results in a variable degree of upper airway obstruction, and bronchospasm and increased mucus secretion compromise the lower airways. Bronchospasm is more marked in asthmatic patients or in those taking beta-blockers.

Aetiology

The triggering agent can be identified in about three-quarters of patients presenting to emergency departments. ⁴

In one childhood series the triggers were:⁵

In a more recent series, food anaphylaxis comprised 85% of presentations to a tertiary paediatric hospital emergency department.⁶

Clinical features

Symptoms occur along a continuum, from reactions that are primarily cutaneous in nature, through mild to moderate anaphylactic reactions that may have respiratory symptoms but without tachypnoea or hypotension, to severe life-threatening anaphylaxis with hypotension and hypoxia.

In children, cutaneous (90% of cases) and respiratory (80% of cases) manifestations occur earlier and are more common than gastrointestinal and cardiovascular manifestations. In ‘food’ anaphylaxis, gastrointestinal symptoms are more frequent, whereas cardiovascular symptoms are rare. Gastrointestinal symptoms include abdominal discomfort and vomiting. Gastrointestinal features are associated with cardiovascular rather than respiratory manifestations. The cutaneous features of pruritus, erythema, urticaria, and angio-oedema occur in nearly all children. These are commonly the first symptoms experienced, occurring within minutes following allergen exposure. Life-threatening symptoms and signs include loss of consciousness, syncope, dizziness, light-headedness, cerebral dysfunction, hypotension, hypoxia, stridor, cyanosis, and laryngeal oedema.

Table 22.5.1 lists the frequency of the presenting symptoms and signs in children admitted to hospital for anaphylaxis.

Biphasic anaphylactic reactions are defined as worsening of symptoms, requiring new therapy, after the resolution of anaphylaxis, and occur in 3–20% of anaphylactic presentations.^5,6 The reaction usually occurs 4–10 hours after the initial event; however, it has been described up to 48 hours later. Biphasic reactions are not accurately predicted from the initial clinical features. The more severe the initial anaphylactic event and/or its inadequate treatment with adrenaline, the more likely a biphasic reaction will occur.⁶

Investigations

Anaphylaxis is a clinical diagnosis, and investigations do not have a role in the acute management. On occasions, it may be difficult to differentiate anaphylaxis from other cardiac, respiratory, or neurological episodes. In this situation, determination of plasma levels of mast cell mediators (histamine and mast cell tryptase) may provide additional diagnostic help.⁷ Mast cell tryptase occurs in an alpha form that is constitutively released and a beta form that is released only following mast cell activation. In anaphylaxis, mediators are elevated in approximately 50% of patients presenting to emergency departments and in approximately 80% of fatal cases. Histamine elevation is better correlated than tryptase with the severity of the symptoms. However, histamine and tryptase may also be elevated in milder cases of acute allergic reactions with cutaneous reaction alone.

It is necessary to collect blood for histamine within 10 minutes to 1 hour following the reaction, as histamine levels peak at 5–10 minutes and decline rapidly to baseline by 15–60 minutes. Tryptase should be collected not later than 6 hours after the initial reaction. Peak levels of beta-tryptase occur at 1–2 hours and decline with a half-life of approximately 2 hours. If blood is collected in the initial 30 minutes after a reaction, tryptase elevation may not be detected. Tryptase is stable and can be identified in plasma or serum stored at room temperature for several days. Interpretation of tryptase levels is often difficult and is improved if baseline levels are available; however, in the majority of cases this is unlikely to be present. Comparison with a baseline may be helpful in cases with recurrent presentation where the diagnosis is uncertain.

The reliability of measuring mast cell tryptase post mortem has been questioned, because elevation of tryptase may be seen in control cases where death has occurred from other causes. Constitutionally raised levels of mast cell tryptase in the non-acute phase have been associated with an increased incidence of severe reactions following insect stings, suggesting that the patients most likely to develop anaphylaxis may have either an increased mast cell mass or an increased mast cell releasability.

The investigation of allergic triggers requires referral to a consultant allergist for performance of appropriate skin prick and blood tests to determine the presence of specific IgE antibodies. Serum allergen specific IgE levels determined via UniCAP® above which patients have a >95% chance of having an immediate IgE-mediated reaction⁸ have been determined for some foods (e.g. cow’s milk, egg, peanut, wheat). It is not possible to predict the severity of a future allergic reaction based on the skin prick test size or allergen specific IgE levels.