Anaphylaxis

Anaphylaxis is a severe, life threatening, systemic type one hypersensitivity reaction. It is characterised by rapid onset of symptoms affecting the airway, breathing or circulation.

It is a medical emergency requiring immediate recognition and treatment with adrenaline as the first line intervention. Delay in adrenaline administration is consistently associated with worse outcomes.

Pathophysiology

Antigen crosslinking of IgE bound to mast cells and basophils triggers rapid, massive degranulation with release of histamine, tryptase, leukotrienes and prostaglandins.

This produces widespread vasodilation, increased vascular permeability, smooth muscle contraction (bronchospasm) and mucosal oedema. Together these cause the characteristic combination of airway compromise, respiratory distress and circulatory collapse.

A minority of episodes occur through non IgE mediated mast cell activation (direct degranulation by certain drugs or physical triggers), producing a clinically identical picture managed in the same way.

The clinical criteria for anaphylaxis are met by rapid onset, typically within minutes to under two hours of exposure to the causative trigger, of:

• Symptoms affecting skin or mucosa (urticaria, flushing, angioedema), together with either
• Airway or breathing compromise (stridor, wheeze, breathlessness, hypoxia), or
• Circulatory compromise (hypotension, collapse, reduced consciousness).

Common triggers include food (particularly nuts, shellfish and eggs), insect stings, medications (antibiotics, particularly beta lactams, and neuromuscular blocking agents in the perioperative setting), and latex.

Gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) frequently accompany the more classically recognised features, and a sense of impending doom is a recognised and important prodromal symptom.

Biphasic reactions, in which symptoms recur hours after apparent initial resolution without further antigen exposure, occur in a meaningful minority and underpin the recommendation for a period of observation following successful initial treatment.

Severity can escalate extremely rapidly, and the absence of skin findings does not exclude anaphylaxis, an important point since a proportion of severe reactions present with predominant airway or circulatory compromise without prominent cutaneous manifestations.

Diagnosis is clinical and immediate, made at the bedside based on the rapid onset and combination of symptoms, without waiting for any laboratory confirmation, since treatment must begin without delay.

Serum tryptase, if measured, is most useful when taken as a series (immediately, at one to two hours and at twenty four hours after symptom onset). It supports a retrospective diagnosis and helps distinguish anaphylaxis from other causes of collapse.

A normal tryptase does not exclude the diagnosis, particularly with food triggered reactions.

Specific IgE testing or skin prick testing, performed after full recovery (typically four to six weeks later) rather than during the acute episode, helps identify the causative allergen and guide future avoidance.

Referral to an allergy specialist following any episode of anaphylaxis is appropriate for confirmation of the trigger, development of a personalised management plan, and consideration of desensitisation where relevant.

Intramuscular adrenaline, given into the anterolateral thigh, is the first line and most important treatment. Give it immediately on recognition of anaphylaxis, without waiting for other interventions.

The adult dose is five hundred micrograms (0.5 millilitres of 1 in 1000 solution), repeated after five minutes if there is inadequate response. Paediatric dosing is weight based.

Call for emergency assistance immediately, and position the patient supine with legs elevated (or in a position of comfort if breathless, avoiding sudden standing which can precipitate cardiovascular collapse from redistribution of the reduced circulating volume).

High flow oxygen, intravenous fluid resuscitation with rapid crystalloid boluses for hypotension, and continuous monitoring of airway, breathing, circulation and oxygen saturation are established alongside or immediately following the initial adrenaline dose.

Antihistamines and corticosteroids are considered as adjunctive treatments once the initial life threatening features have been addressed with adrenaline, though neither should delay or substitute for adrenaline administration, and evidence for their benefit in altering the acute course or preventing biphasic reactions is limited.

Refractory anaphylaxis not responding to repeated intramuscular adrenaline requires escalation to intravenous adrenaline infusion under specialist critical care guidance, given the significant risk of arrhythmia with intravenous bolus dosing outside a monitored setting.

Patients on beta blockers may show reduced response to adrenaline, and glucagon is considered as an adjunctive treatment in this specific circumstance given its adrenaline independent mechanism of action.

Observation for a minimum period following resolution of symptoms (commonly six to twelve hours, longer for severe reactions or those with asthma) is recommended given the risk of biphasic reaction.

Every patient should be discharged with a prescription for and training in the use of an adrenaline autoinjector, a written personalised anaphylaxis action plan, and referral to an allergy specialist for trigger identification and long term management planning.