Anaphylaxis

Introduction

Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction. It is a clinical diagnosis, made at the bedside from the pattern of onset and organ systems involved, not from a laboratory test - waiting for confirmation before treating is a fatal mistake.¹

Most cases are IgE-mediated, triggered by re-exposure to an allergen that cross-links IgE on mast cells and basophils, causing massive release of histamine and other mediators. This produces vasodilatation, increased vascular permeability, bronchospasm and mucosal oedema - the physiological basis for every feature of the reaction and every element of its treatment.

Common triggers include food (nuts, shellfish, milk, egg), drugs (antibiotics, particularly penicillins, and neuromuscular blocking agents used in anaesthesia), insect venom (wasp and bee stings) and latex. In a significant minority no trigger is ever identified.

Not every severe reaction is IgE-mediated. Some agents - opioids, NSAIDs, radiocontrast media and vancomycin among them - can trigger direct, non-immune mast cell degranulation (previously called an anaphylactoid reaction). Clinically the presentation and emergency management are identical, since both pathways converge on the same mediator release; the distinction mainly matters for subsequent allergy testing, which relies on demonstrating IgE sensitisation and so is less useful after a non-IgE reaction.

• Risk factors for a more severe reaction: poorly controlled asthma, mastocytosis or a raised baseline tryptase, concurrent beta-blocker or ACE inhibitor use, and a rapid-onset reaction to a parenteral trigger
• Perioperative anaphylaxis is a distinct and heavily examined scenario: neuromuscular blocking agents are the commonest cause, followed by chlorhexidine, latex and antibiotics given at induction. It is easy to miss because the patient is anaesthetised, unable to report symptoms, and drapes hide skin changes - unexplained hypotension, tachycardia, bronchospasm or a rising airway pressure after induction should trigger this diagnosis

Recognition

The Resuscitation Council UK definition rests on three features occurring together: sudden onset and rapid progression of symptoms, life-threatening airway, breathing or circulatory problems, and (usually, but not always) skin or mucosal changes.²

Onset is typically within minutes of exposure for intravenous triggers (drugs given parenterally) and can take longer - up to an hour or more - for ingested triggers such as food. A faster onset generally predicts a more severe reaction.

History

• What was eaten, given or applied in the preceding hour, and the timing relative to symptom onset
• Any previous reaction to the same or a related exposure, and how it was treated
• Known allergies, atopy (asthma, eczema, hay fever) and any prior anaphylaxis
• Current medications, particularly beta-blockers and ACE inhibitors, which can worsen severity or blunt the response to adrenaline
• Whether an adrenaline auto-injector was used before arrival, and when

Immediate management

Management follows the same ABCDE structure as any acutely unwell patient, but with one crucial addition made as the very first step: intramuscular adrenaline.

1. Remove the trigger if possible (stop an infusion, remove a stinger) without delaying treatment
2. Call for help - resuscitation team or 999
3. Give IM adrenaline into the anterolateral thigh, mid-third, without waiting for IV access
4. Position the patient - flat with legs raised for hypotension, sitting up if breathing is the main problem, left lateral if pregnant or unconscious; never sit or stand a hypotensive patient up suddenly
5. High-flow oxygen (15 L/min via non-rebreathe mask)
6. IV fluid bolus (500-1000 mL balanced crystalloid) for hypotension, reassessing after each bolus
7. Reassess every 5 minutes and repeat IM adrenaline if there is no improvement

Repeat the IM dose after 5 minutes if there is no improvement in the patient's condition - most patients respond to one or two doses. If a third dose is needed, or the patient remains unstable, this is refractory anaphylaxis and needs critical care or anaesthetic input for an IV adrenaline infusion.

Second-line treatment

UK guidance changed in 2021: antihistamines and corticosteroids are no longer considered essential emergency treatment for anaphylaxis. They do not act quickly enough to reverse the airway, breathing or circulatory compromise that defines the reaction, and steroids in particular were removed from the algorithm because there is no good evidence they reduce biphasic reactions or improve outcome.²

• A non-sedating oral antihistamine may be considered after the initial resuscitation, once the patient is stable, mainly to treat persistent urticaria or itch
• Routine corticosteroids are no longer recommended
• Bronchodilators (nebulised salbutamol) if wheeze persists despite adrenaline
• Glucagon (1-2 mg IV/IM) for patients on beta-blockers who do not respond to adrenaline, since beta-blockade can blunt the adrenaline response

Investigations

Investigation is secondary to treatment and should never delay it. Mast cell tryptase is the main test used to support the diagnosis retrospectively, since it is unhelpful acutely.

• Mast cell tryptase - ideally three samples: as soon as possible after treatment starts, at 1-2 hours, and a baseline at 24 hours or at follow-up; a rise and fall supports mast cell degranulation, though a normal level does not exclude anaphylaxis
• Clinical monitoring - continuous ECG, pulse oximetry and repeated blood pressure throughout

Observation and discharge

A biphasic reaction is a recurrence of symptoms after apparent resolution, without further allergen exposure, thought to occur in a meaningful minority of cases. It usually happens within several hours but has been reported up to 72 hours later, which underpins the observation periods recommended before discharge.

Before discharge

• Prescribe and demonstrate use of two adrenaline auto-injectors, to be carried at all times
• Give a written anaphylaxis action plan
• Advise on allergen avoidance where a trigger is known or suspected
• Advise wearing medical alert identification
• Refer to a specialist allergy clinic for confirmation of the trigger and ongoing management - this is not optional, as most patients who die from anaphylaxis were never referred after a previous reaction
• Consider whether the reaction should be reported (for example via the MHRA Yellow Card scheme if drug-induced)

Differential diagnosis

• Vasovagal syncope - pallor and bradycardia rather than tachycardia, no respiratory or skin involvement, rapid spontaneous recovery lying flat
• Asthma exacerbation - wheeze without the circulatory or mucosal features of anaphylaxis
• Panic attack - can mimic breathlessness and a sense of impending doom, but without objective airway, breathing or circulatory compromise
• Hereditary or bradykinin-mediated angioedema - angioedema without urticaria or itch, does not respond to adrenaline or antihistamines, needs C1 esterase inhibitor concentrate
• Scombroid poisoning - histamine toxicity from poorly stored fish, mimicking an allergic reaction but not immune-mediated

Cardiac arrest in anaphylaxis

Anaphylaxis can progress to cardiac arrest despite treatment, usually through a combination of profound vasodilatation, capillary leak causing severe hypovolaemia, and airway obstruction. Standard ALS applies, with modifications: consider prolonged CPR since the underlying process may resolve, give larger and more rapid IV fluid boluses to counter the capillary leak, and continue IV adrenaline (now dosed as in cardiac arrest rather than the IM anaphylaxis dose) as part of the resuscitation.

Red flags

Prognosis

With prompt recognition and treatment, most anaphylactic reactions resolve completely. Fatalities are rare but occur, most often from delayed or omitted adrenaline, inadequate observation leading to a missed biphasic reaction, or failure to arrange follow-up and auto-injector provision after a first reaction. The single most important determinant of outcome is how quickly adrenaline is given.

UK data suggest food-triggered fatal reactions are more common in teenagers and young adults, often occurring outside the home and sometimes with a delay before adrenaline is administered - a pattern that has driven public health measures such as clearer food allergen labelling and wider availability of auto-injectors in schools and public venues. Drug-induced fatal anaphylaxis, by contrast, more often occurs in a healthcare setting where the reaction begins within minutes of exposure and adrenaline should be immediately to hand.