How to Diagnose Anaphylaxis
Anaphylaxis is diagnosed clinically when any one of three NIAID/FAAN criteria is fulfilled, and this diagnosis must be made rapidly without waiting for laboratory confirmation, as treatment with intramuscular epinephrine should never be delayed. 1
Clinical Diagnostic Criteria (NIAID/FAAN)
Anaphylaxis is highly likely when any ONE of the following three criteria is met 1:
Criterion 1: Acute Skin/Mucosal Involvement PLUS Respiratory or Cardiovascular Compromise
- Sudden onset (minutes to several hours) of skin or mucosal symptoms (generalized hives, itching, flushing, swollen lips-tongue-uvula) 1
- AND at least one of the following:
Criterion 2: Two or More Organ Systems After Allergen Exposure
Two or more of the following occurring suddenly after exposure to a likely allergen 1:
- Skin/mucosal symptoms (generalized hives, itch-flush, swollen lips-tongue-uvula) 1
- Respiratory symptoms (shortness of breath, wheeze, cough, stridor, hypoxemia) 1
- Reduced blood pressure or end-organ dysfunction (hypotonia/collapse, incontinence) 1
- Gastrointestinal symptoms (crampy abdominal pain, vomiting) 1
Criterion 3: Isolated Hypotension After Known Allergen Exposure
Reduced blood pressure after exposure to a known allergen for that patient 1:
- Adults: Systolic BP <90 mm Hg or >30% decrease from baseline 1
- Infants (1 month-1 year): Systolic BP <70 mm Hg 1
- Children (1-10 years): Systolic BP <[70 mm Hg + (2 × age)] 1
- Children (11-17 years): Systolic BP <90 mm Hg 1
Essential Clinical Assessment
Initial Evaluation Components
Assess the following systems systematically 1:
- Level of consciousness (impairment suggests hypoxia) 1
- Upper and lower airways: dysphonia, stridor, cough, wheezing, shortness of breath 1
- Cardiovascular system: hypotension with or without syncope, cardiac arrhythmias, tachycardia 1
- Skin: diffuse or localized erythema, pruritus, urticaria, angioedema 1
- Gastrointestinal system: nausea, vomiting, diarrhea 1
- Additional symptoms: lightheadedness, headache, uterine cramps, feeling of impending doom, unconsciousness 1
Critical Diagnostic Pitfalls
Skin findings may be absent in 10-20% of anaphylaxis cases, particularly in rapidly progressive reactions with cardiovascular collapse—diagnosis and treatment should never wait for cutaneous manifestations 2, 3. Tachycardia is typical, but may be absent in patients with conduction defects, increased vagal tone (Bezold-Jarisch reflex), or those taking sympatholytic medications 1.
Key Differential Diagnoses to Exclude
Vasovagal Reaction (Most Common Mimic)
The vasodepressor reaction is most commonly confused with anaphylaxis 1:
- Urticaria is absent 1
- Heart rate is typically bradycardic (not tachycardic) 1
- Bronchospasm or breathing difficulty is generally absent 1
- Blood pressure is usually normal or increased 1
- Skin is typically cool and pale (not flushed) 1
Other Conditions to Consider
Additional diagnoses that may present with abrupt collapse 1:
- Acute anxiety (panic attack, hyperventilation syndrome) 1
- Myocardial dysfunction 1
- Pulmonary embolism 1
- Systemic mast cell disorders 1
- Foreign-body aspiration 1
- Acute poisoning 1
- Hypoglycemia 1
- Seizure disorder 1
Clinical Judgment Overrides Criteria
Epinephrine administration is not limited to patients meeting NIAID/FAAN diagnostic criteria—clinical judgment takes precedence 1. For example, a patient undergoing immunotherapy who develops generalized urticaria immediately after injection may appropriately receive epinephrine if impending anaphylaxis is suspected, despite not yet meeting formal criteria 1. When in doubt, it is better to give epinephrine 3.
Isolated allergen-associated urticaria that may respond to antihistamines should be distinguished from anaphylaxis requiring prompt epinephrine 1.
Laboratory Testing Role
Anaphylaxis is a clinical diagnosis that must be made rapidly; confirmatory testing has poor sensitivity and should never delay treatment 3. Serum tryptase levels can be obtained when the clinical diagnosis is unclear, reflecting mast cell degranulation, but results are not available in time to guide acute management 4.
Timing and Progression
The more rapidly anaphylaxis develops after exposure, the more likely the reaction is severe and potentially life-threatening 3. Symptoms typically begin within minutes to several hours of allergen exposure 1, 5. Anaphylaxis occurs as a continuum—symptoms not immediately life-threatening may progress rapidly unless treated promptly 1.