Definition and epidemiology
Anaphylaxis is an acute, severe, systemic hypersensitivity reaction with rapid onset that can be fatal. It typically involves two or more organ systems (skin/mucosa, respiratory, cardiovascular, gastrointestinal) or isolated hypotension after exposure to a known allergen.
- Lifetime prevalence is estimated at roughly 1-2% of the population, with rising incidence over recent decades.
- Common triggers vary by age: foods (peanut, tree nuts, shellfish, milk, egg) predominate in children; insect stings and medications (antibiotics, NSAIDs, neuromuscular blockers) are more common triggers in adults.
- Fatal anaphylaxis is rare but underreported; risk factors for fatality include asthma, delayed epinephrine administration, and upright posture during the reaction.
- Anaphylaxis is diagnosed clinically; do not wait for tryptase results to treat.
- Intramuscular epinephrine in the anterolateral thigh is first-line and should never be delayed.
- Antihistamines and steroids are adjuncts only, not substitutes for epinephrine.
- Biphasic reactions can occur hours later, so observe patients after initial treatment.
- Beta-blocker use can blunt the response to epinephrine; consider glucagon for refractory hypotension.
- Serum tryptase can be normal in food-triggered anaphylaxis, so a normal level does not rule it out.
- Urticaria/angioedema may be absent in up to 10-20% of true anaphylaxis cases.
- All patients should be discharged with an epinephrine auto-injector and allergy follow-up.
Etiology and risk factors
Common triggers
- Foods: peanuts, tree nuts, shellfish, fish, milk, egg (most common in children)
- Insect venom: bee, wasp, hornet stings
- Medications: beta-lactam antibiotics, NSAIDs, neuromuscular blocking agents, biologic agents
- Latex, radiocontrast media
- Idiopathic anaphylaxis (no identifiable trigger in a subset of patients)
Risk factors for severity
- Pre-existing asthma or other chronic respiratory disease
- Mastocytosis or elevated baseline tryptase
- Beta-blocker or ACE inhibitor use (can worsen severity and blunt response to epinephrine)
- Exercise-induced or augmented reactions (e.g., food-dependent exercise-induced anaphylaxis)
Pathophysiology
Most anaphylaxis is IgE-mediated: on re-exposure to an allergen, antigen cross-links IgE bound to high-affinity FcεRI receptors on mast cells and basophils, triggering degranulation. Released mediators include histamine, tryptase, leukotrienes, prostaglandins, and platelet-activating factor (PAF).
- These mediators cause vasodilation, increased vascular permeability (leading to hypotension and edema), bronchoconstriction, and increased mucus secretion.
- Non-IgE-mediated (previously called "anaphylactoid") reactions can occur via direct mast cell activation (e.g., opioids, radiocontrast, vancomycin) or complement activation, producing a clinically identical picture.
- PAF is thought to be a major contributor to the severity and fatality of reactions, correlating with hypotension and bronchospasm severity.
Clinical features
Onset is typically within minutes to 1-2 hours of exposure; faster onset generally correlates with greater severity.
- Skin/mucosal: urticaria, flushing, pruritus, angioedema (present in up to 90% of cases but can be absent)
- Respiratory: stridor, wheezing, dyspnea, throat tightness, hoarseness
- Cardiovascular: hypotension, tachycardia, dizziness, syncope, shock
- Gastrointestinal: nausea, vomiting, crampy abdominal pain, diarrhea
- Biphasic reactions: recurrence of symptoms hours after apparent resolution, occurring in a minority of patients, which is why observation periods are recommended after treatment.
Diagnosis
Diagnosis is primarily clinical and should not be delayed for laboratory confirmation. Widely used clinical criteria (e.g., NIAID/FAAN) support the diagnosis when any ONE of the following is met:
- Acute onset of illness with skin/mucosal involvement plus respiratory compromise or hypotension
- Two or more of the following rapidly after likely allergen exposure: skin/mucosal involvement, respiratory compromise, hypotension, persistent GI symptoms
- Hypotension after exposure to a known allergen for that patient
Supporting tests
- Serum tryptase: can be drawn at onset, 1-2 hours, and 24 hours after symptom resolution (baseline) to support diagnosis; most useful when elevated during the acute event compared to baseline
- Tryptase can be normal, especially in food-triggered reactions, so a normal level does not exclude anaphylaxis
- Allergy workup (skin testing, specific IgE) is done later, after the acute episode, to identify the trigger
Differential diagnosis
| Condition | Distinguishing feature |
|---|---|
| Vasovagal syncope | Bradycardia, pallor, no urticaria or respiratory symptoms |
| Acute asthma exacerbation | Isolated bronchospasm without skin or cardiovascular involvement |
| Panic attack | No objective hypotension, urticaria, or hypoxia |
| Hereditary angioedema | Recurrent angioedema without urticaria, poor response to epinephrine/antihistamines |
| Scombroid poisoning | Occurs after eating spoiled fish, histamine-like symptoms without true allergic mechanism |
| Carcinoid syndrome | Flushing and diarrhea but with chronic recurrent pattern, not acute allergen-triggered |
| Mastocytosis/mast cell activation syndrome | Recurrent episodes, elevated baseline tryptase |
Management
Immediate steps
- Remove or stop the trigger if possible
- Administer intramuscular epinephrine into the anterolateral thigh immediately; this is the first-line and most time-critical treatment
- Call for emergency help and position the patient supine with legs elevated (or left lateral if pregnant or vomiting); avoid sudden standing due to risk of empty ventricle syndrome
- Repeat epinephrine doses every 5-15 minutes if no improvement
- High-flow supplemental oxygen
- IV fluid resuscitation with crystalloids for hypotension
Adjunctive therapy (never first-line, never a substitute for epinephrine)
- H1 antihistamines (e.g., diphenhydramine) for urticaria and pruritus
- H2 antihistamines may be added in some protocols
- Corticosteroids, though evidence for preventing biphasic reactions is weak and guidelines increasingly de-emphasize routine use
- Inhaled bronchodilators (albuterol) for persistent bronchospasm
- Glucagon may be considered for patients on beta-blockers with refractory hypotension unresponsive to epinephrine
Disposition and follow-up
- Observe for several hours (commonly 4-6 hours, longer for severe reactions or biphasic risk factors) given the possibility of biphasic reactions
- Prescribe self-injectable epinephrine (two doses) and provide an anaphylaxis action plan on discharge
- Refer to allergy/immunology for trigger identification and consideration of desensitization (e.g., venom immunotherapy) where applicable
Complications and prognosis
- Cardiovascular collapse and shock refractory to treatment
- Airway obstruction from laryngeal edema requiring advanced airway management
- Hypoxic end-organ injury from prolonged hypotension or respiratory failure
- Biphasic reactions (minority of cases), underscoring the need for observation
- With prompt epinephrine administration, most patients recover fully; delayed treatment is the main modifiable risk factor for death
- Risk of recurrence is significant without identification and avoidance of the trigger, making allergy follow-up essential
ABCDE of anaphylaxis management: Airway, Breathing, Circulation, Drugs (epinephrine first), Exposure/Elevate legs.
Practice questions
1. A 24-year-old woman develops facial swelling, diffuse hives, and wheezing 10 minutes after eating shrimp at a restaurant. Her blood pressure is 88/52 mmHg and heart rate is 118/min. Which of the following is the most appropriate immediate step in management?
2. A 55-year-old man with a history of hypertension on metoprolol is stung by a bee and develops hypotension, urticaria, and bronchospasm. He is given two appropriate doses of intramuscular epinephrine with minimal improvement in blood pressure. Which of the following is the most appropriate next agent to administer?
3. A 10-year-old boy with known peanut allergy receives appropriate treatment for anaphylaxis in the emergency department and improves fully within an hour. He is observed and discharged after 2 hours feeling well. Which of the following best describes a risk associated with this disposition plan?
Frequently asked questions
What causes anaphylaxis?
Anaphylaxis is most often caused by an IgE-mediated allergic reaction to foods, insect stings, or medications, which triggers mast cell and basophil degranulation. Common food triggers include peanuts, tree nuts, and shellfish, while drugs like antibiotics and NSAIDs are frequent causes in adults. Non-allergic mechanisms, such as direct mast cell activation by certain drugs or contrast media, can produce an identical clinical picture.
What are the first symptoms of anaphylaxis?
The earliest symptoms are usually skin and mucosal changes like hives, flushing, and itching, often accompanied by a sense of throat tightness or anxiety. These can progress within minutes to respiratory symptoms such as wheezing or stridor and cardiovascular symptoms like dizziness or fainting from dropping blood pressure. Gastrointestinal symptoms like cramping and vomiting may also appear early, especially with food triggers.
How is anaphylaxis diagnosed?
Anaphylaxis is diagnosed clinically based on the rapid onset of symptoms involving two or more organ systems, or hypotension alone after exposure to a known allergen. Diagnosis should never be delayed for lab testing. Serum tryptase levels drawn during and after the event can support the diagnosis retrospectively but are not required to initiate emergency treatment.
Is anaphylaxis curable?
Anaphylaxis itself is not a chronic disease to be cured, but an acute reaction that resolves with prompt treatment, usually without lasting effects. The underlying allergy that causes it is typically lifelong unless the patient undergoes successful desensitization therapy, such as venom immunotherapy for insect sting allergy. Avoidance of the identified trigger and carrying epinephrine remain the mainstay of long-term management.
Anaphylaxis vs anaphylactoid reaction, what is the difference?
Anaphylaxis classically refers to an IgE-mediated reaction requiring prior sensitization, while an anaphylactoid reaction (now often called a non-IgE-mediated or non-allergic reaction) results from direct mast cell activation or complement activation without prior sensitization. Clinically, the two are indistinguishable and are treated identically. Modern terminology groups both under the single term anaphylaxis based on clinical presentation rather than mechanism.
Key drugs
Related conditions and differentials
Sources and further reading
StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: T78.2
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.