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Allergy and Immunology· Topic 1.1 Anaphylaxis· 1.1.1
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Anaphylaxis

Anaphylaxis is an acute, potentially fatal systemic hypersensitivity reaction from massive mast cell and basophil mediator release, presenting within minutes as skin, respiratory, cardiovascular, and gastrointestinal involvement after allergen exposure. It is a clinical, treat-first diagnosis, and intramuscular epinephrine is the immediate life-saving therapy.

6 min readReviewed 2026-07-19

Key facts

Nature
Acute systemic IgE-mediated (type I) hypersensitivity
Skin involvement
Urticaria or angioedema in ~90%
First-line treatment
IM epinephrine 0.3-0.5 mg, repeat q5-15 min
Shock mechanism
Distributive (vasodilation, capillary leak)
Supportive test
Serum tryptase within 1-2 h
Late risk
Biphasic reaction hours later
Disposition
Two epinephrine autoinjectors + allergy referral

Overview

  • Definition: anaphylaxis is an acute, potentially fatal systemic hypersensitivity reaction caused by rapid, massive release of mediators from mast cells and basophils, producing multi-system involvement within minutes of exposure.
  • Cardinal presentation: sudden urticaria or angioedema (present in about 90 percent) with respiratory compromise and/or hypotension after contact with an allergen.
  • Why it is an emergency: it can kill quickly through upper-airway obstruction and distributive shock, and delayed epinephrine is the strongest predictor of death.
  • First-line treatment: intramuscular epinephrine given immediately is the only intervention shown to reduce mortality; antihistamines and glucocorticoids are adjuncts, not substitutes.
  • Late hazard: a biphasic reaction can recur hours after apparent resolution, so patients are observed.

Epidemiology

  • Common triggers: foods (peanut, tree nuts, shellfish, milk, egg), Hymenoptera stings, drugs (beta-lactams, NSAIDs), and latex; a proportion is idiopathic.
  • Age pattern: food is the leading trigger in children, whereas drugs and insect stings predominate in adults.
  • At-risk groups: prior anaphylaxis, atopy, and asthma, which worsens severity.

Risk factors

  • Prior anaphylaxis or known allergy: the strongest predictor of a future episode.
  • Asthma, especially poorly controlled: associated with more severe, fatal reactions.
  • Specific exposures: foods, Hymenoptera stings, beta-lactams and NSAIDs, latex, perioperative agents, and radiocontrast media.
  • Mast cell disease: systemic mastocytosis or an elevated baseline tryptase.
  • Beta-blocker or ACE inhibitor use: more severe reactions that are harder to treat.

Pathophysiology

  • IgE-mediated mechanism (type I): allergen cross-links specific IgE on mast cells and basophils, triggering degranulation.
  • Non-IgE direct activation: agents such as opioids, vancomycin, and radiocontrast can directly activate mast cells and produce an identical picture.
  • Mediator release: histamine, prostaglandin D2, leukotrienes, and tryptase drive vasodilation, increased vascular permeability, and bronchoconstriction.
  • Distributive shock: hypotension arises from peripheral vasodilation and capillary leak in a hyperdynamic state, not from impaired cardiac contractility.

Clinical features

  • Skin and mucosa (about 90 percent): urticaria, flushing, pruritus, and angioedema.
  • Respiratory: throat tightness, stridor, wheeze, dyspnea, and hypoxemia from laryngeal edema and bronchospasm.
  • Cardiovascular: hypotension, tachycardia, syncope, and shock.
  • Gastrointestinal: crampy abdominal pain, vomiting, and diarrhea.
  • Tempo: onset within minutes to a few hours, and the faster the onset the more severe the reaction.
  • Biphasic course: symptoms can recur hours after initial resolution without re-exposure.

Differential diagnosis

  • Vasovagal syncope: bradycardia and pallor without urticaria, bronchospasm, or true shock.
  • Bradykinin-mediated angioedema (hereditary or ACE inhibitor): swelling without urticaria or pruritus and a poor response to epinephrine (Angioedema).
  • Acute asthma exacerbation: wheeze and dyspnea without urticaria or hypotension (Asthma).
  • Septic or other distributive shock: fever and an infection source rather than acute allergen exposure (Sepsis).
  • Scombroid poisoning: histamine from spoiled fish producing a flushing and urticarial mimic, but affecting others who ate the same fish and resolving without epinephrine.
  • Panic attack or vocal cord dysfunction: subjective throat closure without objective skin or airway findings.
  • Carcinoid syndrome: episodic flushing and diarrhea over a chronic course.
  • Mast cell activation syndrome or mastocytosis: recurrent episodes with elevated tryptase.
  • Acute coronary syndrome or arrhythmia: cardiovascular collapse without allergic features.

Diagnosis

  • Diagnose clinically and treat first, using the standard criteria (any one of three fulfills the diagnosis):
    • Acute onset over minutes to hours of skin or mucosal involvement plus either respiratory compromise or hypotension or end-organ dysfunction.
    • Two or more of the following after exposure to a likely allergen: skin or mucosal signs, respiratory compromise, hypotension, or persistent gastrointestinal symptoms.
    • Hypotension after exposure to a known allergen for that patient.
  • Supportive laboratory test, serum tryptase: draw within 1 to 2 hours of onset (it peaks about 1 hour and can stay elevated for roughly 5 hours); an elevated level supports the diagnosis, but a normal level does not exclude it and is common in food-triggered anaphylaxis.
  • After recovery, identify the trigger: refer to allergy for specific IgE or skin testing, and measure a baseline tryptase to screen for mastocytosis.
  • Never delay treatment for testing: epinephrine is given on clinical grounds.

Clinical pearl. Anaphylaxis is a treat-first diagnosis: give intramuscular epinephrine the moment criteria are met. A normal tryptase never rules it out because it is frequently normal in food-triggered reactions, and waiting for a lab result or for a second organ system to declare itself is how patients die.

Management

  • First, give intramuscular epinephrine to stabilize the patient: 0.3 to 0.5 mg IM (0.01 mg/kg, 1 mg/mL concentration) into the anterolateral thigh, repeated every 5 to 15 minutes as needed; there is no absolute contraindication in anaphylaxis.
  • Position and oxygenate: lay the patient supine with legs elevated (avoid sudden upright posture, which can precipitate fatal empty-ventricle arrest) and give high-flow oxygen.
  • Restore volume: 1 to 2 L of IV crystalloid bolus for hypotension.
  • If refractory to repeated IM dosing: start an epinephrine IV infusion 0.05 to 0.5 mcg/kg/min, titrated to response, and add another vasopressor if shock persists.
  • If on a beta-blocker and refractory: glucagon 1 to 5 mg IV over 5 minutes, then a 5 to 15 mcg/min infusion.
  • Secure the airway early: prepare for intubation when there is stridor or airway angioedema.
  • Add adjuncts (never in place of epinephrine): an H1 antihistamine (diphenhydramine 25 to 50 mg IV) with an H2 blocker (famotidine 20 mg IV) for cutaneous symptoms, inhaled albuterol for bronchospasm, and a glucocorticoid (methylprednisolone 1 to 2 mg/kg IV) with no acute mortality benefit.
  • Observe for a biphasic reaction: monitor for 4 to 6 hours, longer after severe or refractory episodes.
  • Discharge safely: prescribe two epinephrine autoinjectors, provide an anaphylaxis action plan, arrange allergy referral, and counsel trigger avoidance.

Complications

  • Death: from upper-airway obstruction or refractory distributive shock, usually with delayed epinephrine.
  • Biphasic reaction: recurrence hours after initial recovery.
  • Hypoxic-ischemic injury and arrhythmia: consequences of prolonged hypoxia or shock.
  • Protracted anaphylaxis: symptoms persisting despite treatment.

Prognosis

  • Excellent with prompt epinephrine: outcomes are strongly tied to how quickly epinephrine is given.
  • Fatal reactions cluster: in asthmatics, in adolescents and young adults with food allergy, and when treatment is delayed.
  • Recurrence risk is lifelong: for the identified trigger, mandating a carried autoinjector.

Prevention

  • Avoid the identified trigger: the foundation after allergy evaluation.
  • Carry two epinephrine autoinjectors at all times: and train the patient and caregivers in their use.
  • Venom immunotherapy for Hymenoptera-sting anaphylaxis: given over 3 to 5 years, reduces the risk of a future systemic reaction to roughly 5 percent.
  • Document drug allergies and use graded challenge, premedication, or desensitization when an implicated agent is unavoidable.
  • Optimize asthma control: to reduce the severity of any future reaction.

Key points

  • Anaphylaxis is a clinical, treat-first diagnosis made by the three-criteria set, not by laboratory testing.
  • Intramuscular epinephrine 0.3 to 0.5 mg in the anterolateral thigh, repeated every 5 to 15 minutes, is first-line and mortality-reducing; antihistamines and steroids are adjuncts only.
  • Skin findings occur in about 90 percent, but their absence does not exclude anaphylaxis.
  • Watch for biphasic reactions and observe for 4 to 6 hours.
  • Discharge with two autoinjectors and allergy referral, and offer venom immunotherapy for sting-triggered anaphylaxis.

Practice questions

Board-style vignettes on this article, free with it. Pick an answer to see why each choice is right or wrong.

Vignette
A 47-year-old woman is evaluated in the emergency department 35 minutes after generalized hives, throat tightness and lightheadedness began within minutes of eating cashew chicken. She has hypertension treated with lisinopril. Temperature is 36.8 °C (98.2 °F), blood pressure is 72/38 mm Hg, pulse rate is 134/min, respiration rate is 28/min, and oxygen saturation is 91% with oxygen by mask. Generalized urticaria is present. There is no stridor. Diffuse expiratory wheezing is heard. The extremities are warm. Over the past 25 minutes she has received epinephrine 0.5 mg intramuscularly in the thigh three times at 5-minute intervals, 2 L of saline and nebulized albuterol; she remains hypotensive. Which of the following is the most appropriate next step in management?
Vignette
high-yield
A 52-year-old woman is evaluated in the outpatient infusion center for itching, hives, tongue swelling, chest tightness and dizziness that began 4 minutes after the start of her first dose of intravenous ampicillin. She has hypertension treated with metoprolol succinate 100 mg daily. Temperature is 37.0 °C (98.6 °F), blood pressure is 82/50 mm Hg, pulse rate is 96/min, respiration rate is 26/min, and oxygen saturation is 92% breathing ambient air. She is speaking in full sentences. Urticarial wheals cover the trunk and arms, and the tongue is swollen. There is no stridor. Diffuse expiratory wheezes are heard bilaterally. The infusion has been stopped. Which of the following is the most appropriate initial treatment?
Vignette
high-yield
A 29-year-old man is evaluated in the emergency department for hives, wheezing and lightheadedness that began 15 minutes after he ate shrimp. He has mild intermittent asthma treated with albuterol as needed and no prior allergic reactions. On arrival 25 minutes after symptom onset, temperature is 36.9 °C (98.4 °F), blood pressure is 86/52 mm Hg, pulse rate is 124/min, respiration rate is 24/min, and oxygen saturation is 93% breathing ambient air. Urticarial wheals cover the trunk, and diffuse expiratory wheezes are heard. He receives intramuscular epinephrine 0.5 mg, intravenous saline, diphenhydramine and famotidine. Fifteen minutes later, blood pressure is 118/72 mm Hg and wheezing has resolved. Which of the following is the most appropriate test to confirm the diagnosis?

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