What are the clinical criteria for diagnosing anaphylaxis?

Diagnosing Anaphylaxis

Anaphylaxis is diagnosed clinically when any one of three NIAID/FAAN 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

Criterion 1: Skin/Mucosal Involvement Plus One Additional System

Sudden onset (minutes to hours) of skin or mucosal symptoms (generalized hives, itching, flushing, swollen lips/tongue/uvula) AND at least one of the following: 1, 2

• Respiratory compromise: shortness of breath, wheeze, cough, stridor, or hypoxemia 1
• Reduced blood pressure or end-organ dysfunction: hypotonia (collapse), syncope, or incontinence 1, 3

Criterion 2: Multi-System Involvement After Allergen Exposure

Two or more of the following occurring suddenly after exposure to a likely allergen: 1, 2

• 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
• Persistent gastrointestinal symptoms (crampy abdominal pain, vomiting) 1, 2

Criterion 3: Isolated Hypotension After Known Allergen

Reduced blood pressure after exposure to a known allergen for that specific patient: 1, 2

• Adults: systolic BP <90 mm Hg or >30% decrease from baseline 1
• Infants (1 month to 1 year): systolic BP <70 mm Hg 1
• Children (1-10 years): systolic BP <[70 mm Hg + (2 × age in years)] 1
• Children >10 years: systolic BP <90 mm Hg 1

Critical Clinical Considerations

Validation and Performance

The NIAID/FAAN criteria were prospectively validated in emergency department settings, demonstrating a positive likelihood ratio of 3.26 and negative likelihood ratio of 0.07, confirming their reliability for real-world diagnosis. 1, 2

Anaphylaxis Without Skin Findings

Skin findings are absent in 10-20% of anaphylaxis cases—do not delay diagnosis or treatment waiting for cutaneous manifestations. 3 Anaphylaxis can present with isolated respiratory compromise or hypotension after allergen exposure. 1

Clinical Judgment Supersedes Criteria

Epinephrine administration is not limited to patients meeting formal diagnostic criteria. 2, 4 For example, a patient developing generalized urticaria immediately after allergen immunotherapy may warrant epinephrine for impending anaphylaxis, even before full criteria are met. 1 Clinical judgment takes precedence over rigid adherence to criteria. 4

Timing and Progression

Symptoms typically begin within minutes to several hours after allergen exposure. 4 The more rapidly anaphylaxis develops, the more likely it is severe and life-threatening. 4 Mild initial symptoms can progress rapidly to fatal reactions, making early recognition essential. 4

Essential Clinical Assessment Components

Systematically evaluate: 4

• Level of consciousness 4
• Upper and lower airways (stridor, wheeze, respiratory distress) 4
• Cardiovascular system (blood pressure, pulse, perfusion) 4
• Skin (urticaria, angioedema, flushing) 4
• Gastrointestinal system (cramping, vomiting, diarrhea) 4
• Additional symptoms (lightheadedness, headache, uterine cramps) 4

Key Differential Diagnoses to Exclude

Vasovagal Reaction (Most Common Mimic)

Distinguished by: 4

• Absence of urticaria 4
• Bradycardia (not tachycardia) 4
• Normal or increased blood pressure (not hypotension) 4

Other Mimics

Consider acute anxiety, myocardial dysfunction, pulmonary embolism, systemic mast cell disorders, foreign-body aspiration, acute poisoning, hypoglycemia, and seizure disorder. 4

Common Pitfalls to Avoid

• Do not wait for laboratory confirmation—anaphylaxis is a clinical diagnosis requiring immediate action. 4
• Do not distinguish between isolated allergen-associated urticaria and anaphylaxis—isolated urticaria may respond to antihistamines, but anaphylaxis requires immediate epinephrine. 1
• Do not delay epinephrine while waiting for additional criteria to develop—impending anaphylaxis warrants treatment based on clinical suspicion. 2, 4
• Do not assume skin involvement is required—10-20% of cases lack cutaneous findings. 3