Anaphylaxis

1. History

• Exposure history: Identify the suspected trigger — foods (peanut, tree nuts, shellfish, milk, egg), medications (antibiotics, NSAIDs, anesthetics), insect stings (Hymenoptera), latex, contrast dye, or unknown [2][5]
• Timing: Onset typically within minutes to 1–2 hours of exposure; alpha-gal reactions may be delayed up to 10 hours [3]
• Symptom progression: Rapid onset of multisystem involvement — skin (urticaria, flushing, angioedema), respiratory (dyspnea, stridor, wheeze), GI (cramping, vomiting), cardiovascular (dizziness, syncope) [6-7]
• Cofactors that lower threshold: Exercise, alcohol, concurrent illness, fever, menstruation, NSAIDs, aspirin [8]
• Prior episodes: History of previous anaphylaxis, severity, triggers, and response to treatment
• Important negatives: Absence of skin findings does not exclude anaphylaxis — up to 10–20% of cases lack cutaneous involvement [8]

2. Alarm Features

• Stridor, hoarseness, tongue/uvula swelling → impending airway obstruction
• Hypotension (SBP <90 mmHg in adults, or >30% decrease from baseline) [6-7]
• Hypoxemia, cyanosis, respiratory arrest
• Altered mental status, syncope, incontinence → end-organ hypoperfusion
• Rapid progression of symptoms despite initial treatment
• Refractory anaphylaxis: Failure to respond to appropriate epinephrine dosing — accounts for <0.5% of severe cases but carries a 26.2% fatality rate [9]

3. Medications

• First-line: Intramuscular epinephrine (see Treatment Plan below) [3-4]
• Adjunctive only (after epinephrine):
  • H1 antihistamines (cetirizine preferred over diphenhydramine for less sedation and longer duration) [6]
  • H2 antihistamines (famotidine)
  • Inhaled beta-2 agonists (albuterol) for bronchospasm [6]
  • Glucagon for patients on beta-blockers with refractory hypotension [10]
• Corticosteroids: No proven benefit in acute anaphylaxis; do not reliably prevent biphasic reactions [6][8]
• Medications that increase risk of severe/fatal anaphylaxis: Beta-blockers (blunt epinephrine response), ACE inhibitors [2]
• Contraindicated: Do NOT substitute antihistamines or corticosteroids for epinephrine as initial treatment [6][11]

4. Diet

• Common food triggers: Peanuts, tree nuts, shellfish, fish, cow's milk, egg, wheat, soy, sesame [2][5]
• Alpha-gal syndrome: Red meat allergy following tick bite — delayed onset (3–6 hours); consider in recurrent idiopathic anaphylaxis with tick exposure history [3]
• Food-dependent exercise-induced anaphylaxis (FDEIA): Occurs when exercise follows ingestion of culprit food (commonly wheat) within 4–6 hours [8]
• Long-term: Strict avoidance of identified food allergens; label reading education; cross-contamination awareness

5. Review of Systems

• Skin: Urticaria, flushing, pruritus, angioedema (most common presenting feature)
• Respiratory: Dyspnea, wheeze, stridor, cough, chest tightness, throat tightness, hoarseness
• Cardiovascular: Lightheadedness, presyncope/syncope, palpitations, chest pain
• GI: Nausea, vomiting, abdominal cramping, diarrhea
• Neurologic: Anxiety, sense of impending doom, confusion, altered consciousness
• Genitourinary: Incontinence (sign of end-organ dysfunction)

6. Collateral History and Family History

• Witnesses to the event can clarify timing, exposure, and symptom progression
• Prior allergy testing results, previous anaphylaxis episodes, and prior ED visits
• Family history: Atopy, asthma, hereditary alpha-tryptasemia (HαT — autosomal dominant, associated with elevated baseline tryptase and increased anaphylaxis risk) [3][9]
• Mast cell disorders: Family or personal history of mastocytosis [12]
• Social context: Occupation (food handlers, healthcare workers with latex exposure), outdoor activities (insect sting risk)

7. Risk Factors

• Severe/fatal anaphylaxis risk factors: [2]
  • Coexisting asthma (especially poorly controlled)
  • Mast cell disorders (systemic mastocytosis, elevated baseline tryptase)
  • Older age and underlying cardiovascular disease
  • Peanut/tree nut allergy
  • Drug-induced reactions
  • Concurrent beta-blocker or ACE inhibitor use
• Biphasic reaction risk factors: [9][13]
  • Severe initial presentation (hypotension, hypoxia)
  • Multiple doses of epinephrine required
  • Delayed epinephrine administration
  • Unknown trigger
  • Wide pulse pressure
  • History of prior biphasic reaction

8. Differential Diagnosis

• Acute asthma exacerbation — isolated lower airway; no urticaria/angioedema/hypotension
• Vasovagal syncope — bradycardia (vs. tachycardia in anaphylaxis), no urticaria/angioedema
• Panic attack/hyperventilation — no objective findings (urticaria, hypotension, wheeze)
• Hereditary angioedema — recurrent angioedema without urticaria; does NOT respond to epinephrine or antihistamines
• ACE inhibitor–induced angioedema — isolated angioedema, no urticaria
• Carcinoid syndrome — episodic flushing, diarrhea; elevated 5-HIAA
• Systemic mastocytosis — recurrent flushing, hypotension; elevated baseline tryptase [12]
• Vocal cord dysfunction — inspiratory stridor, no urticaria
• Septic/cardiogenic shock — fever, infection source; or cardiac history
• Foreign body aspiration — acute onset, no systemic features
• Scombroid fish poisoning — histamine-mediated; flushing, urticaria after fish ingestion [8][14]

9. Past Medical History

• Prior anaphylaxis episodes (triggers, severity, treatment response)
• Asthma — strongest risk factor for fatal food-induced anaphylaxis
• Atopic dermatitis, allergic rhinitis, food allergies
• Mast cell disorders, elevated baseline tryptase
• Cardiovascular disease (limits hemodynamic reserve)
• Medications: beta-blockers, ACE inhibitors, NSAIDs
• Prior allergy testing and immunotherapy history

10. Physical Exam

• Vitals: Tachycardia, hypotension, tachypnea, hypoxemia; note that bradycardia may occur in patients on beta-blockers
• Skin: Generalized urticaria, flushing, angioedema (lips, tongue, uvula, periorbital)
• HEENT: Tongue/uvula swelling, oropharyngeal edema, rhinorrhea, conjunctival injection
• Lungs: Wheeze, stridor, decreased air movement, accessory muscle use
• Cardiovascular: Tachycardia, weak pulses, delayed capillary refill, hypotension
• Abdomen: Diffuse tenderness (mast cell–mediated GI involvement)
• Neuro: Altered mental status, agitation, obtundation (late sign of shock)
• Pediatric pearl: Hypotension may be a late finding in children — tachycardia alone may indicate shock [15]

11. Lab Studies

• Serum tryptase (most important lab): [3][9][16]
  • Draw within 2 hours of symptom onset (peaks at 30–60 min, returns to baseline by ~2–4 hours)
  • Elevated if >11.4 ng/mL, but more sensitive: acute tryptase ≥ (1.2 × baseline) + 2 ng/mL
  • An acute/baseline ratio of ≥1.685 may optimize sensitivity and specificity (94.4% each) [17]
  • Draw a baseline tryptase at follow-up when patient is well
  • If baseline tryptase ≥8 ng/mL → evaluate for hereditary alpha-tryptasemia and clonal mast cell disease [3]
• CBC: May show hemoconcentration from capillary leak
• BMP: Assess renal function, electrolytes
• Lactate: If concern for shock
• ABG/VBG: If respiratory compromise
• Tryptase has pooled sensitivity of only ~49% and specificity of ~82% — a normal tryptase does NOT rule out anaphylaxis [16]

12. Imaging

• Imaging is generally NOT required for the diagnosis of anaphylaxis — it is a clinical diagnosis
• Chest X-ray: Consider if persistent respiratory symptoms, concern for pneumothorax, or alternative diagnosis (pulmonary edema, aspiration)
• CT neck/soft tissue: If concern for deep-space airway edema not responding to treatment
• Chest CT/CTA: Only if pulmonary embolism is in the differential

13. Special Tests

• NIAID/FAAN diagnostic criteria (3-criteria clinical tool) — validated and widely used [6-7]
• Serum tryptase with the "Rule of Twos" (see Lab Studies above) [9]
• Allergy testing (outpatient, after recovery):
  • Skin prick testing and/or serum-specific IgE to suspected triggers
  • Performed ≥4 weeks after the event to avoid false negatives during the refractory period [9]
• Alpha-gal IgE: If delayed-onset anaphylaxis after red meat ingestion [3]
• Bone marrow biopsy: Consider in recurrent idiopathic anaphylaxis, severe insect sting anaphylaxis, or elevated baseline tryptase — to evaluate for systemic mastocytosis [9]
• REMA score: Predictive tool for clonal mast cell disease in patients with Hymenoptera anaphylaxis [9]

14. ECG

• Obtain ECG in all patients with cardiovascular symptoms (hypotension, syncope, chest pain) or those receiving IV epinephrine
• Findings to watch for:
  • ST-segment changes (epinephrine-induced demand ischemia or Kounis syndrome — allergic acute coronary syndrome)
  • Arrhythmias (tachyarrhythmias, bradycardia in beta-blocker users)
  • QTc prolongation
• Arrhythmia and acute coronary syndrome after IM epinephrine are rare (only 7 case reports in the literature) [8]
• Continuous cardiac monitoring recommended for patients receiving IV epinephrine or with refractory anaphylaxis [18]

15. Assessment

• Anaphylaxis is a clinical diagnosis — there are no pathognomonic symptoms, exam findings, or lab results [3]
• Diagnosis is highly likely when any 1 of 3 NIAID/FAAN criteria is met: [6-7]
  • Acute skin/mucosal involvement + respiratory compromise OR hypotension
  • ≥2 organ systems involved rapidly after exposure to a likely allergen
  • Hypotension after exposure to a known allergen
• Severity stratification: Laryngeal, respiratory, or cardiovascular involvement carries the highest mortality risk [3]
• Biphasic reactions occur in ~1–7% of cases (up to 20% in some series), typically within 12 hours [9][13][19]
• Complications: Airway obstruction, cardiovascular collapse, cardiac arrest, hypoxic brain injury, death

16. Treatment Plan

The following algorithm outlines the outpatient management approach:

17. Disposition

• Observation minimum: [2][14][20]
  • Nonsevere, prompt response, low risk: Observe ≥1 hour (some guidelines recommend ≥4 hours)
  • Moderate severity: Observe 4–6 hours
  • Severe (respiratory compromise): Observe 6–8 hours
  • Hypotension or cardiovascular compromise: Observe 12–24 hours
• Admission criteria: [7]
  • Refractory anaphylaxis requiring multiple epinephrine doses or IV epinephrine
  • Persistent hypotension despite treatment
  • Severe respiratory compromise requiring intubation
  • Significant comorbidities (asthma, cardiovascular disease, mast cell disorder)
  • Lack of access to epinephrine or emergency services after discharge
• ICU admission: Refractory anaphylaxis, hemodynamic instability requiring vasopressors, intubation
• Allergy/immunology consultation: Recurrent anaphylaxis, idiopathic anaphylaxis, elevated baseline tryptase, suspected mast cell disorder [9]

18. Follow Up / Return Precautions

• At discharge: [3][7]
  • Prescribe 2 epinephrine autoinjectors with hands-on training for patient and caregivers
  • Provide a written anaphylaxis action plan
  • Educate on trigger avoidance
• Follow-up timing:
  • Primary care: Within 1–2 weeks to document allergy history, ensure EAI prescription, and review prevention strategies [3]
  • Allergist referral: Within 4–6 weeks for formal allergy testing (skin prick/specific IgE) and consideration of immunotherapy (e.g., venom immunotherapy) [9]
  • Baseline tryptase should be drawn at follow-up when patient is well [8]
• Return precautions — seek immediate care for:
  • Recurrence of any symptoms (urticaria, swelling, breathing difficulty, dizziness) — biphasic reaction can occur up to 72 hours [2]
  • Use of epinephrine autoinjector
  • Any new exposure to the suspected trigger
• Expected course: Most uniphasic reactions resolve within hours with appropriate treatment; ~90% respond to 1–2 doses of epinephrine [8]