When do you diagnose anaphylaxis?

When to Diagnose Anaphylaxis

Diagnose anaphylaxis immediately when any one of three clinical criteria is met: (1) acute skin/mucosal involvement plus respiratory compromise or hypotension, (2) two or more organ systems involved after allergen exposure, or (3) isolated hypotension after known allergen exposure. 1, 2

The Three Diagnostic Criteria (NIAID/FAAN)

The diagnosis requires fulfillment of any single criterion from the following three options:

Criterion 1: Skin/Mucosal Involvement Plus One Major System

• Acute onset (minutes to hours) of generalized hives, itching, flushing, or swollen lips/tongue/uvula PLUS at least one of: 1, 2
  • Respiratory compromise: dyspnea, wheeze, bronchospasm, stridor, reduced peak flow, or hypoxemia 1
  • Reduced blood pressure or end-organ dysfunction: hypotonia, collapse, syncope, or incontinence 1

Criterion 2: Two or More Organ Systems After Allergen Exposure

• Rapid onset after exposure to a likely allergen, with two or more of the following: 1, 2
  • Skin/mucosal symptoms (hives, itch, flush, swelling) 1
  • Respiratory compromise 1
  • Reduced blood pressure or end-organ dysfunction 1
  • Persistent gastrointestinal symptoms (crampy abdominal pain, vomiting) 1

Criterion 3: Isolated Hypotension After Known Allergen

• Reduced blood pressure alone after exposure to a known allergen for that specific patient: 1, 2
  • Adults: systolic BP <90 mmHg **or** >30% decrease from baseline 1
  • Infants (1 month-1 year): systolic BP <70 mmHg 1, 2
  • Children (1-10 years): systolic BP <70 mmHg + (2 × age in years) 1, 2
  • Children >10 years: systolic BP <90 mmHg 1, 2

Critical Clinical Pearls

Skin Findings Are NOT Required

• 10-20% of anaphylaxis cases present without any cutaneous manifestations—do not wait for hives or flushing to make the diagnosis. 2, 3, 4
• Isolated respiratory compromise or isolated hypotension after allergen exposure (especially insect stings or inhalant exposures) can represent anaphylaxis without skin involvement. 2, 3

Clinical Judgment Overrides Formal Criteria

• Administer epinephrine whenever anaphylaxis is suspected, even if formal NIAID/FAAN criteria are not yet fully met. 2, 5, 3
• For example, immediate generalized urticaria after allergen immunotherapy warrants epinephrine despite not meeting full criteria. 2

Timing Matters for Severity

• Symptoms typically begin within minutes to several hours after allergen exposure. 1, 2, 3, 6
• More rapid onset correlates with higher severity and greater risk of life-threatening outcomes—median time to arrest is 5 minutes for iatrogenic reactions, 15 minutes for envenomations, and 30 minutes for foods. 2, 4

Validation of These Criteria

• The NIAID/FAAN criteria were prospectively validated in emergency department settings with a positive likelihood ratio of 3.26 and negative likelihood ratio of 0.07, confirming strong diagnostic utility. 2, 3
• These criteria are endorsed by the American Academy of Allergy, Asthma & Immunology, American College of Allergy, Asthma & Immunology, and World Allergy Organization as the standard for clinical practice. 2, 5, 3

Common Pitfalls to Avoid

Do Not Delay for Laboratory Confirmation

• Anaphylaxis is a clinical diagnosis—do not wait for serum tryptase levels or other laboratory tests before treating. 3, 6, 7
• Tryptase can be obtained when the diagnosis is unclear, but treatment must not be delayed. 6, 7

Distinguish from Vasovagal Reaction

• Vasovagal reaction is the most common mimic: look for bradycardia (not tachycardia), absence of urticaria, and normal or increased blood pressure. 3
• Anaphylaxis typically presents with tachycardia and hypotension. 3

Recognize Biphasic Reactions

• Biphasic anaphylaxis (recurrence after complete resolution) occurs in 4-5% of cases, typically within 1-78 hours after initial reaction. 1
• Patients require observation for 4-12 hours depending on severity and risk factors. 1, 6

Even Resolved Symptoms Warrant Diagnosis

• A patient who arrives in the emergency department asymptomatic but with a history meeting NIAID/FAAN criteria should still receive an anaphylaxis diagnosis, even though acute epinephrine is no longer indicated. 1