2. Anaphylaxis: diagnosis and management

Simon G A Brown, Raymond J Mullins and Michael S Gold
Med J Aust 2006; 185 (5): 283-289. || doi: 10.5694/j.1326-5377.2006.tb00563.x
Published online: 4 September 2006
How common is anaphylaxis?

Anaphylaxis is uncommon but not rare, with new cases arising at rates of between 8.4 and 21 per 100 000 patient-years.2-4 An Australian survey of parent-reported allergy and anaphylaxis found that 1 in 170 school children had suffered at least one episode of anaphylaxis.5 Another Australian study showed that, in areas where native Myrmecia ant species are prevalent, 1 in 50 adults have experienced anaphylaxis after stings from native Myrmecia species (Box 1) or honeybees.6 Deaths from anaphylaxis are uncommon, estimated to occur at a rate of 1 per 3 million population per year.7 In areas where sting allergy is common, the death rate may be higher than this. Hospital-based studies suggest a death rate in the order of 1 per 100–200 episodes of anaphylaxis treated in an emergency department.8,9

There is some evidence that the incidence of food allergy and anaphylaxis — like that of allergic rhinitis and atopic dermatitis — may be increasing.10-12

What causes anaphylaxis?

Food, insect venoms or medication trigger most cases of anaphylaxis, with a variable proportion of patients experiencing idiopathic anaphylaxis (in which extensive evaluation fails to identify an underlying cause) (Box 2). In emergency department studies, food allergy is the commonest cause in children — responsible for about 80% of anaphylactic reactions in which the cause has been identified13 — whereas, in adults, foods are implicated in only 20%–30% of cases.8,9 This difference is reflected in mortality statistics: the median ages for lethal reactions to foods and to insect venoms or medications are 22–24 years and 55–67 years, respectively.14

What happens in anaphylaxis?

Anaphylactic mediators cause vasodilation, fluid extravasation, smooth muscle contraction and increased mucosal secretions. Death may occur from hypoxaemia (due to upper airway angioedema, bronchospasm and mucus plugging) and/or shock (due to massive vasodilation, fluid shift into the extravascular space and depressed myocardial function).17 While compensatory tachycardia in response to hypotension is considered a characteristic feature, sudden bradycardia with cardiovascular collapse and cardiac arrest may occur before any skin features become apparent.18 The cause of this phenomenon is unclear, but it is an important clinical feature to recognise in order to avoid making an initial misdiagnosis of a “panic attack” or “vasovagal reaction” in cases where dyspnoea, nausea, anxiety, and bradycardia may occur just before cardiovascular collapse.

Suspecting the diagnosis
Clinical features

The clinical features of anaphylaxis are summarised in Box 3. Skin features are almost universal if reactions are closely observed, but erythema (and even angioedema) may be subtle and missed if not carefully looked for (Box 4). Respiratory symptoms are more common in children, whereas cardiovascular and cutaneous symptoms dominate in adults.13 In part, this may be related to the higher frequency of atopy, asthma and food allergy in children.13 Pre-existing lung disease is associated with an increased frequency of respiratory compromise from any cause,6,9 and poorly controlled asthma appears to be the main risk factor for childhood death due to food allergy.19

Confusion, collapse, unconsciousness and incontinence are strongly associated with the presence of hypotension and hypoxia. In adults, the occurrence of dyspnoea, profuse sweating, nausea, vomiting and abdominal pain are also significant, as they correlate with the presence of hypotension.9

Acute management
Ancillary medications

Medications such as antihistamines, H2 receptor antagonists, corticosteroids and antileukotrienes have no proven impact on the immediate and dangerous effects of anaphylaxis, although they may ameliorate mild allergic reactions confined to the skin. The only registered antihistamine for parenteral use in Australia, promethazine, can worsen vasodilation and hypotension, and its use is not advised.17,31 Until human research clarifies the potential risks and benefits of antihistamines, it is prudent to restrict antihistamine use to oral, selective, non-drowsiness-inducing antihistamines, with or without oral or injectable corticosteroids, for the symptomatic relief of mild skin symptoms. Based on their use in treating asthma, corticosteroids are commonly given to reduce the risk of biphasic anaphylaxis (see below), although there is currently no evidence to support their effectiveness for this purpose.


The time course of anaphylaxis can be classified as “uniphasic”, “protracted” or “biphasic”.33 Although most reactions respond rapidly to treatment and do not recur (uniphasic reactions), an observation period is recommended. This is because, in some patients, symptoms may fail to improve or may worsen as the effect of adrenaline wears off (protracted anaphylaxis) or may return after early resolution (biphasic reaction). No clinical feature consistently identifies patients at risk of a biphasic reaction. Expert consensus is that a reasonable length of observation after symptom resolution is 4–6 hours in most patients, with more prolonged observation in those with severe or refractory symptoms and those with reactive airway disease, as most fatalities associated with anaphylaxis occur in these patients.1

Poorly controlled asthma is the main risk factor for death in children. Age over 35 years and previous severe reactions are the main risk factors for hypotension and death in adults.

After the acute episode

Before examining the surrounding circumstances to define a cause for the patient’s symptoms (Box 2), it is important to first determine whether anaphylaxis occurred by carefully reviewing the available documentation. Short-lived bouts of urticaria and/or angioedema lasting less than 12 hours should prompt suspicion of an allergic cause, although on their own they do not satisfy a definition of anaphylaxis. As typical cutaneous features may be absent in up to 20% of cases, anaphylaxis should be considered in the differential diagnosis of any episode of severe, acute-onset respiratory distress, bronchospasm or cardiovascular collapse (Box 9).

Details of exposure to potential triggers, including occupational allergens (eg, latex) and cofactors, in the preceding 8 hours should be recorded while memory of the event is fresh. Almost all anaphylactic reactions to insect venoms or to food or medication occur within 1 and 6 hours, respectively.2

Medical practitioners should record the presence of known food or drug hypersensitivity and consider the possibility of accidental exposure. Ask patients about symptoms of contact urticaria (eg, during food preparation) or itching in the mouth and throat after eating certain foods (oral allergy syndrome). The latter indicates an allergy to structurally similar proteins in pollen and in some fruit and vegetables.2 If an insect sting has occurred, factors that may help identify the cause are the insect’s appearance, the presence of a stinger left in the skin (pathognomonic for honeybee sting) and the location where the sting occurred (stings by jack jumper ants or bulldog ants are more common in bushland).


In-vitro testing for allergen-specific IgE (using a radioallergosorbent test [RAST] or ImmunoCAP [Phadia AB, Uppsala, Sweden]) is a useful initial screening test for a variety of allergens. In-vitro testing has limitations because the test lacks sensitivity and is limited by the range of allergens available and the ability to claim Medicare rebates for only four allergens at a time.

Skin prick testing, to assess sensitisation to food, and skin prick testing (or sometimes intradermal testing), to assess allergy to medications or insect venom, are more sensitive than in-vitro testing. As these carry a small risk of inducing anaphylaxis, they should only be carried out in an environment in which resources for treating anaphylaxis are available. Measurement of total IgE and in-vitro testing using food mixes frequently provide misleading or irrelevant results and should not be requested.

There is currently no test to confirm tick bite allergy. Skin testing for jack jumper ant allergy is not yet available outside the Royal Hobart Hospital in Tasmania, although an in-vitro test is available from SouthPath Laboratories in South Australia (this detects only 80% of cases, and, while the subject of ongoing research, there is no validated test to detect allergy to related ant species).

Some drug reactions (eg, to NSAIDS, radiographic contrast agents) are independent of IgE, and there are numerous difficulties in assessing some cases of antibiotic allergy. To establish a diagnosis in cases in which the causative agent is in doubt, challenge testing under controlled conditions may sometimes be required, although a negative challenge test does not always exclude the diagnosis.

There is no scientific validity for “alternative” therapies such as cytotoxic or Vega testing, hair analysis and kinesiology, and their use should be discouraged.34

Long-term management

Anaphylaxis to insect stings can be prevented with venom immunotherapy,23 which reduces the risk of anaphylaxis from repeated stings and is associated with an improved quality of life compared with carrying an EpiPen alone.24 Attempts to modify the severity of food allergy using similar techniques have thus far failed, although novel methods of inducing tolerance hold some promise for the future.35

For most patients, anaphylaxis is a disorder for which the risk of relapse is chronic but the event itself is unpredictable.2 The mainstays of long-term management of anaphylaxis include:

A number of resources for patients and health care professionals, including guidelines for dealing with anaphylaxis in specific settings such as schools and childcare centres, prescribing guidelines and written action plans, are available on the ASCIA website ( The EpiPen doses commonly recommended by specialist bodies (such as ASCIA) differ from those in the package insert. ASCIA recommends prescribing EpiPen Junior (0.15 mg) for patients weighing 10–20 kg and EpiPen (0.3 mg) for patients weighing over 20 kg.

Wearing a MedicAlert bracelet (Australia MedicAlert Foundation, Adelaide, SA) may give attending medical or paramedical personnel access to additional information about known allergies, reduce the risk of administration of allergenic medication, and facilitate earlier recognition and treatment of anaphylaxis.

Despite their widespread clinical use, medications such as antihistamines and corticosteroids have no proven efficacy in preventing or treating anything other than mild cutaneous allergic symptoms. Furthermore, the cost of maintaining or using these medications in people with anaphylaxis due to other causes needs to be balanced against the cost of purchasing an additional EpiPen. Large doses of adrenaline may be required to treat hypotensive anaphylaxis,18 so Australians living in remote areas may need additional supplies beyond the single EpiPen unit subsidised by the current Pharmaceutical Benefits Scheme for individuals over 17 years of age. Even if an initial EpiPen injection has been effective, patients should seek emergency medical care without delay. Patients who live or work in remote areas should consider having access to means of summoning emergency assistance, such as a mobile telephone or, in some cases, an emergency satellite beacon.

When to refer

Specialist evaluation is recommended after a diagnosis of possible anaphylaxis — to identify or confirm the cause, to educate regarding appropriate avoidance strategies, to help in drafting an emergency action plan and to advise whether immunotherapy is appropriate. There is anecdotal evidence that certain medications used to manage blood pressure and heart problems (α-blockers, β-blockers and ACE inhibitors) may worsen anaphylaxis or interfere with the action of adrenaline administered in an emergency. However, this poorly defined risk needs to be balanced against the proven benefits that these medications provide. For patients taking cardiac medications, the relative risks and benefits of their use should be considered in consultation with an allergist and/or other specialists.

Despite the frightening nature of anaphylactic episodes, compliance with advice to avoid known triggers and to carry and use injectable adrenaline is nowhere near 100%.2 Denial and “acting out” by teenagers is also common, and peer pressure or bullying at school may prompt some patients to take unnecessary risks. Review from time to time or after further episodes offers an opportunity to re-educate patients on the use of EpiPen and to ensure that the device is renewed at appropriate intervals. Psychological morbidity and negative impact on quality of life are not uncommon in patients and their caregivers, and some require emotional support and counselling as well as medical advice.

5 Differential diagnosis of anaphylaxis

Tissue swelling

Conditions mimicking upper airway oedema

Flushing syndromes

Neurological syndromes

Other causes of collapse

Acute respiratory distress


ACE = angiotensin-converting enzyme. * Isolated angioedema lacks any other organ or systemic features and thus by definition is not anaphylaxis. Neuroendocrine tumours that secrete vasoactive intestinal polypeptide. “Red man syndrome” is flushing and erythema associated with infusion of vancomycin (or occasionally other antibiotics). It is thought to be due to histamine release, and may be related to dose or infusion rate. § Although included here to prompt a consideration of this underlying disease, systemic mastocytosis is, strictly speaking, a cause of anaphylaxis.

9 Case scenario*

A 63-year-old man experienced sudden cardiovascular collapse at 02:00 in his home. This had been preceded by urticaria and a desire to open his bowels. He was hypotensive, but responded to treatment by paramedics (two 0.5 mg doses of intramuscular adrenaline into the lateral thigh, 5 minutes apart, and rapid intravenous infusion of 2 L saline).

Earlier that evening, he had eaten a buffet meal consisting of bread, various meats, vegetables, salads, sauces and alcohol, had been dancing, and had taken ibuprofen for a headache before retiring to bed at midnight. Concurrent medical problems included ischaemic heart disease (treated daily with a β-blocker).

The patient was observed in the emergency department for 24 hours. There were no ECG changes, and there was no melaena or rise in troponin level. His serum mast cell tryptase level was later reported as 25 μg/L on arrival in the emergency department, falling to 15 μg/L at the time of discharge, confirming the diagnosis of anaphylaxis.


Allergy testing showed no convincing evidence of food hypersensitivity. The diagnostic possibilities of food or drug hypersensitivity were considered, with or without involvement of cofactors like alcohol, exercise and consumption of an NSAID.

The long interval between exercise and onset of a reaction was considered to make exercise an unlikely cofactor. In-hospital graded challenge with ibuprofen was negative. A provisional diagnosis of idiopathic anaphylaxis was made, although it was not possible to completely exclude an unidentified food allergen or summation anaphylaxis (eg, unidentified food allergen ± NSAID ± exercise).

The initial difficulties in resuscitation, requiring two doses of adrenaline and fluid resuscitation, were considered partially attributable to β-blockade. After discussions with his cardiologist, it was concluded that the patient could be safely given an alternative cardiac medication and that the risk from untreated anaphylaxis outweighed the theoretical risk of adrenaline triggering myocardial ischaemia.

The patient was advised to carry and use injectable adrenaline (EpiPen) in an emergency, and to document the circumstances in any future reactions to assist in identifying an avoidable trigger.

ECG = electrocardiogram. NSAID = non-steroidal anti-inflammatory drug.
* This is a fictional case scenario based on similar real-life cases.

  • Simon G A Brown1
  • Raymond J Mullins2
  • Michael S Gold3

  • 1 University of Western Australia and Fremantle Hospital, Fremantle, WA.
  • 2 Australian National University, Canberra, ACT.
  • 3 Women’s and Children’s Hospital and University of Adelaide, Adelaide, SA.



The authors are grateful for the many helpful comments by Dr Bob Heddle.

Competing interests:

None identified.

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