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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Anaphylaxis is a clinical diagnosis; do not wait for labs.
- First-line treatment is intramuscular epinephrine 0.3-0.5 mg of 1 mg/mL solution in the mid-outer thigh.
- Airway edema, wheezing, hypotension, syncope, or GI symptoms after allergen exposure should trigger immediate treatment.
- Antihistamines and corticosteroids are adjuncts only; they do not replace epinephrine.
- Observe for biphasic reaction and discharge with epinephrine auto-injectors, education, and allergy follow-up.
Overview
Anaphylaxis is a severe systemic allergic reaction with rapid onset and possible airway, breathing, circulatory, cutaneous, and gastrointestinal involvement. It is commonly IgE-mediated but can also occur through non-IgE mechanisms. Common triggers include foods, medications, insect stings, latex, and biologic agents. Because deterioration can be abrupt, epinephrine should be administered immediately when anaphylaxis is suspected.
Epidemiology
Lifetime prevalence of anaphylaxis in the United States is estimated at approximately 1-2%. Food triggers predominate in children and young adults, while medications and venom are common in adults. Risk factors for fatal reactions include asthma, delayed epinephrine, cardiovascular disease, beta-blocker use, mast cell disorders, and lack of auto-injector access.
Clinical Features
Symptoms
Pruritus, flushing, urticaria, or sense of impending doom after exposure
Tongue, lip, uvular, or throat swelling; hoarseness; dysphagia
Wheezing, dyspnea, chest tightness, or stridor
Dizziness, syncope, hypotension, or collapse
Cramping abdominal pain, vomiting, or diarrhea after allergen exposure
Anaphylaxis may occur without urticaria, especially in severe cardiovascular presentations
Signs
Hypotension, tachycardia, weak pulses, or shock
Angioedema, urticaria, flushing, or generalized erythema
Wheeze, decreased air entry, hypoxemia, or increased work of breathing
Stridor, drooling, hoarseness, or rapidly progressive oropharyngeal edema
Altered mental status from hypoxia or shock
Investigations
First-line
Clinical assessmentDiagnosis is clinical. Treat immediately when airway, breathing, circulatory, or multisystem involvement follows likely allergen exposure.
Vital signs and continuous monitoringPulse oximetry, cardiac monitoring, blood pressure, respiratory status, and response to epinephrine.
Airway evaluationAssess voice change, stridor, tongue/uvular swelling, drooling, and need for early intubation.
Second-line
Serum tryptaseCan support diagnosis if drawn within 1-2 hours of symptom onset, but normal tryptase does not exclude anaphylaxis and treatment must not wait.
Point-of-care glucose / ECGUse if altered mental status, syncope, chest pain, or older patient with cardiovascular disease.
Specialist
Allergy evaluationOutpatient allergist referral for trigger identification, avoidance plan, venom/food/drug evaluation, and immunotherapy where appropriate.
Management
NIAID Food Allergy Guidelines, AAAAI/ACAAI practice parameters, and ACEP emergency care principles1
Immediate treatment
- Remove trigger and call for help; place patient supine with legs elevated unless respiratory distress requires sitting upright.
- Epinephrine IM into mid-outer thigh: adults 0.3-0.5 mg of 1 mg/mL solution; repeat every 5-15 minutes if needed.
- High-flow oxygen and continuous monitoring.
- Two large-bore IVs; isotonic crystalloid boluses for hypotension.
- Prepare for early airway management if stridor, voice change, progressive edema, or refractory hypoxemia.
2
Adjunctive therapy
- Albuterol nebulizers for bronchospasm after epinephrine.
- H1 antihistamine such as diphenhydramine for urticaria/pruritus; H2 blocker may be added.
- Corticosteroids are often given but have delayed onset and do not treat acute airway or circulatory compromise.
- Glucagon for refractory anaphylaxis in patients taking beta-blockers.
3
Refractory anaphylaxis
- Repeated IM epinephrine while preparing epinephrine infusion in a monitored setting.
- Aggressive IV fluids because distributive shock can involve profound capillary leak.
- Vasopressors such as norepinephrine for persistent hypotension despite epinephrine and fluids.
- Early critical care/anesthesia support for airway or shock.
4
Observation and discharge
- Observe at least 4-6 hours after symptom resolution; longer for severe, refractory, or unknown-trigger reactions.
- Prescribe two epinephrine auto-injectors and teach use before discharge.
- Provide written allergy action plan and strict return precautions.
- Refer to allergy/immunology for trigger evaluation and prevention.
Complications
- Upper airway obstruction: Laryngeal edema can progress rapidly and make delayed intubation difficult
- Distributive shock: Vasodilation and capillary leak can cause cardiovascular collapse
- Biphasic reaction: Recurrence after initial resolution, usually within hours
- Cardiac arrest: Usually from hypoxia, severe bronchospasm, or refractory shock
- Medication error: IV bolus epinephrine at the wrong concentration can cause dangerous tachyarrhythmia or hypertension
USMLE Step 2 CK Exam Tips
- 1Anaphylaxis answer is IM epinephrine first — not antihistamines, not steroids, not observation.
- 2Give epinephrine even if there is no rash when hypotension or airway symptoms follow allergen exposure.
- 3Correct route for initial treatment is intramuscular in the lateral thigh.
- 4Beta-blocker use + refractory anaphylaxis = give glucagon.
- 5Angioedema with urticaria/wheeze/hypotension is treated as anaphylaxis; isolated ACE inhibitor angioedema behaves differently.
- 6Do not discharge without epinephrine auto-injectors and education.
practicetest your knowledge on anaphylaxisApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — emergency medicine and beyond.
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