What are the criteria for diagnosing anaphylaxis?

Diagnostic Criteria for Anaphylaxis

Anaphylaxis is diagnosed when any ONE of three clinical criteria is fulfilled, based on the widely endorsed NIAID/FAAN diagnostic criteria that have been prospectively validated in emergency department settings. 1, 2

The Three Diagnostic Criteria

Criterion 1: Skin/Mucosal Involvement PLUS Respiratory or Cardiovascular Compromise

Acute onset (minutes to several hours) of skin or mucosal tissue involvement (generalized hives, pruritus, flushing, swollen lips/tongue/uvula) AND at least one of the following: 1

• Respiratory compromise: dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory 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

Two or more of the following occurring rapidly (minutes to several hours) after exposure to a likely allergen: 1

• Skin/mucosal tissue involvement (generalized hives, itch/flush, swollen lips/tongue/uvula) 1
• Respiratory compromise (dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia) 1
• Reduced blood pressure or associated symptoms (hypotonia, syncope, incontinence) 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 (minutes to several hours): 1

• Adults: systolic BP <90 mm Hg or >30% decrease from baseline 1
• Infants (1 month to 1 year): systolic BP <70 mm Hg 3
• Children (1-10 years): systolic BP <(70 mm Hg + [2 × age]) 1
• Children >10 years: systolic BP <90 mm Hg or >30% decrease from baseline 1

Critical Clinical Considerations

Skin Symptoms Are Common But Not Required

• Cutaneous manifestations occur in >90% of anaphylaxis cases but their absence does not rule out the diagnosis. 1
• Severe episodes with rapid cardiovascular collapse can occur without any skin findings, particularly when progression is very rapid. 1
• Skin signs may be delayed, absent, or not observed in up to 10-20% of cases, including fatal reactions. 1, 4

Timing and Progression

• Symptoms typically develop within minutes of allergen exposure, though onset can occur up to several hours later. 1
• The more rapidly anaphylaxis develops after exposure, the more likely it is to be severe and life-threatening. 1
• Biphasic reactions occur in 4-5% of cases (range 0.18-14.7%), with symptom recurrence 1-78 hours after initial resolution. 1

Essential Historical Questions

When evaluating for anaphylaxis, specifically ask about: 1

1. Cutaneous manifestations: pruritus, flushing, urticaria, angioedema 1
2. Airway obstruction: upper or lower airway involvement 1
3. Gastrointestinal symptoms: nausea, vomiting, diarrhea 1
4. Cardiovascular symptoms: syncope, presyncope, hypotension 1
5. Temporal relationship: agents encountered before the reaction, timing of symptom onset 1

Additional Symptoms That May Occur

Beyond the core diagnostic criteria, anaphylaxis may present with: 1

• Conjunctival erythema, throat tightness, dysphagia, dysphonia, hoarseness 1
• Dry staccato cough, nasal pruritus, nasal congestion, rhinorrhea 1
• Chest pain, dysrhythmia, feeling of faintness/dizziness 1
• Confusion/altered mental status, sense of impending doom 1
• Pruritus in external auditory canals, uterine contractions 1

Key Differential Diagnoses to Exclude

Vasovagal (Vasodepressor) Reaction - Most Common Mimic

Distinguished from anaphylaxis by: 1

• Bradycardia (not tachycardia) 1
• Absence of urticaria, angioedema, flushing, and pruritus 1
• Cool, pale skin (not flushed) 1
• Normal or increased blood pressure 1
• No bronchospasm or breathing difficulty 1

Important caveat: Bradycardia can occasionally occur in true anaphylaxis due to the Bezold-Jarisch cardioinhibitory reflex, particularly in patients with conduction defects or taking sympatholytic medications. 1

Other Conditions to Consider

• Flushing syndromes: carcinoid, pheochromocytoma, postmenopausal flush, red man syndrome from vancomycin 1
• Postprandial syndromes: scombroid fish poisoning (histamine from spoiled fish), monosodium glutamate reaction 1
• Nonorganic disease: panic attacks, vocal cord dysfunction 1
• Other acute events: acute asthma, foreign body aspiration, pulmonary embolism, myocardial dysfunction, seizure 1

Diagnostic Performance and Clinical Application

Validation of Criteria

The NIAID/FAAN criteria demonstrated a positive likelihood ratio of 3.26 and negative likelihood ratio of 0.07 in prospective emergency department validation studies. 2

Clinical Judgment Supersedes Formal Criteria

• Epinephrine administration should not be delayed while waiting for additional diagnostic criteria to develop if anaphylaxis is suspected. 2
• Clinical judgment determines the need for epinephrine, not strict adherence to diagnostic criteria alone. 2
• A patient presenting to the emergency department with a history meeting diagnostic criteria but completely resolved symptoms should still receive an anaphylaxis diagnosis. 1

Laboratory Testing Has Limited Acute Utility

• Serum tryptase and plasma/urinary histamine metabolites may help confirm the diagnosis retrospectively but are not useful for acute diagnosis. 1
• Blood samples must be drawn with strict timing: tryptase peaks 1-2 hours after symptom onset. 1
• Normal tryptase does not exclude anaphylaxis. 1

Common Pitfalls to Avoid

1. Do not wait for skin symptoms to appear before diagnosing anaphylaxis - up to 20% of cases lack cutaneous findings. 1, 4

2. Do not assume bradycardia rules out anaphylaxis - while typical of vasovagal reactions, it can occur in true anaphylaxis. 1

3. Do not dismiss isolated gastrointestinal symptoms after allergen exposure - when combined with one other system, this meets Criterion 2. 1

4. Do not rely on laboratory tests for acute diagnosis - anaphylaxis is a clinical diagnosis requiring immediate treatment. 5, 6

5. Do not discharge patients immediately after symptom resolution - observe for 4-10 hours depending on severity due to biphasic reaction risk. 1, 5