Diagnosis
There is no universally accepted clinical definition of anaphylaxis. However, a consensus of international experts agreed that anaphylaxis is highly likely when any one of the following three criteria are fulfilled:32
1 - Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalised urticaria, pruritus or flushing, swollen lips/tongue/uvula) and at least one of the following:
- Reduced peak expiratory flow [PEF], hypoxaemia
- Respiratory compromise (e.g., dyspnoea, wheeze/bronchospasm, stridor)
- Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (e.g., palpitations, chest discomfort, syncope, collapse)
2 - Two or more of the following that occur rapidly (minutes to several hours) after exposure to a likely allergen for that patient:
- Involvement of the skin/mucosal tissue (e.g., generalised hives, pruritus, flushing, swollen lips/tongue/uvula)
- Respiratory compromise (e.g., dyspnoea, wheeze-bronchospasm, stridor, reduced PEF, hypoxaemia)
- Reduced BP or associated symptoms (e.g., palpitations, chest discomfort, syncope, collapse)
- Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3 - Reduced BP after exposure to known allergen (minutes to several hours)
- Infants and children: low systolic BP (age specific) or › 30% decrease in systolic BP
- Adults: systolic BP ‹ 90 mm Hg or › 30% decrease from the baseline values of the patient
Anaphylaxis is diagnosed by considering symptoms, time of onset, all exposures and events in the few hours prior to onset of symptoms (e.g. exercise, drug intake, infections, alcohol, stress) and medical history. However, in many cases, the cause remains unknown.
Following an anaphylactic episode, a blood test is performed to measure tryptase, a protein released by the body during anaphylaxis, and histamine; plasma histamine levels should ideally be measured 15 to 60 minutes after the onset of symptoms, while the timeframe for tryptase is 15 minutes to 2 hours after onset. However, these tests are not specific to anaphylaxis and tryptase is a more useful measure for reactions induced by insect stings and drugs than when food is the trigger. There are also number of other biomarkers, e.g. platelet-activating factor and bradykinin, but these are not so widely used.
A number of methods are available to investigate the specific cause of anaphylaxis:
Skin prick test
These should be performed about 6 weeks after the anaphylactic episode to allow time for recovery of mast cell reactivity. A drop of allergen solution is placed on the skin and ‘pushed’ into the epidermis by a sterile needle; the same is done with drops of histamine and saline for comparison. A positive wheal greater than 3 mm in diameter indicates an immune reaction to a specific allergen.33

RAST (Radioallergosorbent test)
A blood sample is used to test for immune reactions to a specific trigger by mixing the sample with the suspected allergen. If an antibody-allergen complex forms, it can be detected using radioactivity-based techniques. The results must therefore be interpreted in the context of the clinical reactions.
| Antibody (kUA/L)34 | PPV* | |
|---|---|---|
| Peanut | > 14 | 100% |
| Milk | > 15 > 5 |
95% 95% (infant ≤2 years) |
| Egg | > 7 > 2 |
98% 95% (infant ≤2 years) |
*Positive predictive value (chance of being allergic)
Although the RAST test can be used in patients who cannot discontinue antihistamines or who have severe atopic dermatitis, it is more expensive and less accurate than the skin prick test, and results are not immediately available.
Oral challenge
Helps determine if there is an intolerance or allergy to a particular food and can also test if a patient has outgrown their allergy. However, these pose some risk to the patient and can be costly.35
Differential diagnosis
Diagnosis of anaphylaxis can be difficult because it presents with symptoms that are common to other conditions, such as generalised urticaria, acute asthma, syncope, food poisoning, panic attack, aspiration of a foreign body and cardiovascular conditions (myocardial infarction, pulmonary embolus) or neurological events (seizure, stroke). Less common conditions include postprandial syndromes, flush syndromes and excess endogenous histamine syndromes, as well as hypovolaemic shock and phaeochromocytoma.
However, taking a thorough history to try to determine possible precipitating factors and careful consideration of the three clinical criteria for diagnosing anaphylaxis should make it clear when anaphylaxis is present.
For example, a patient presenting with a severe asthma exacerbation does not fulfil criterion 1, as there will be no skin involvement. Differential diagnosis is age related to some extent, as foreign body aspiration may be more likely in young children, while MI and stroke are more common in older patients.
- 32 - Bjornsson HM, Graffeo CS. West J Emerg Med 2010;XI(5):456-61.
- 33 - Morris A. Current Allergy & Clinical Immunology 2006;19(1):18-21.
- 34 - Sampson HA. Food allergy. J Allergy Clin Immunol 2003;111:S540-7.
- 35 - Burks W. Pediatrics 2003;111;1617-25.
