Anaphylaxis

Detailed Overview

It is the most severe manifestation of IgE-mediated hypersensitivity (Type I). Upon re-exposure to a specific antigen, cross-linking of IgE on mast cells triggers immediate degranulation. The released histamine, tryptase, and leukotrienes cause massive vasodilation, increased capillary permeability, and smooth muscle spasm. This manifests as airway edema, severe bronchospasm, and distributive shock (hypotension). Without immediate administration of intramuscular epinephrine to reverse vasodilation and bronchodilation, death can occur within minutes. A biphasic reaction, where symptoms return 1 to 72 hours after initial resolution, occurs in up to 20% of patients.

Epidemiology & Demographics

Lifetime prevalence is estimated at 1.6% to 5.1%. Fatalities occur in roughly 0.5% to 1% of cases. Most common triggers vary by age: food in children, and medications or insect stings in adults.

Etiological Mechanism

Foods (peanuts, tree nuts, shellfish, milk, eggs), medications (penicillin, NSAIDs, radiocontrast media), and Hymenoptera venom (bees, wasps) are the most common triggers. Some cases are idiopathic.

Primary Causes

Foods (e.g., Peanuts, Shellfish)

Medications (e.g., Beta-lactam antibiotics)

Insect venom

Latex

• Prior history of anaphylaxis: The strongest predictor of a future episode.
• Co-existing Asthma: Significantly increases the risk of fatal respiratory compromise during anaphylaxis.
• Beta-blocker Therapy: Can make the reaction more severe and refractory to epinephrine treatment.

1. Sensitization: Initial exposure produces antigen-specific IgE antibodies which bind to FcεRI receptors on mast cells and basophils. 2. Re-exposure: Antigen cross-links the bound IgE. 3. Degranulation: Immediate release of preformed mediators (histamine, tryptase, TNF-alpha) and synthesis of lipid mediators (prostaglandins, leukotrienes). 4. Effects: Histamine activates H1 receptors causing bronchoconstriction and smooth muscle contraction (GI cramps), and H1/H2 receptors causing profound vasodilation and increased vascular permeability (urticaria, angioedema, hypotension). 5. Edema of the epiglottis and larynx compromises the upper airway, while distributive shock compromises perfusion to vital organs.

Characteristic Clinical Presentation

• Skin changes: Generalized hives (urticaria), intense itching (pruritus), and flushing. Often the first sign.
• Respiratory Distress: Shortness of breath, wheezing, cough, and a feeling of throat closing (laryngeal edema).
• Gastrointestinal Symptoms: Crampy abdominal pain, nausea, vomiting, and diarrhea.
• Cardiovascular Symptoms: Dizziness, syncope, and an impending sense of doom due to sudden hypotension.

Physical Examination Signs

• Anoxic Brain Injury: Permanent neurological damage due to prolonged shock or airway obstruction.
• Cardiac Arrest: Secondary to hypoxia, severe hypovolemia from third-spacing, or coronary hypoperfusion.

Diagnostic Criteria & Guidelines

Clinical diagnosis based on WAO criteria: Acute onset involving skin/mucosal tissue AND at least one of the following: 1) Respiratory compromise, 2) Reduced BP or end-organ dysfunction, 3) Severe GI symptoms. Alternatively, acute hypotension or bronchospasm occurring shortly after exposure to a known allergen for that patient.

Differential Diagnosis

• Vasovagal Syncope
• Acute Asthma Exacerbation
• Panic Attack
• Carcinoid Syndrome

Laboratory Tests & Biomarkers

• Serum Tryptase: Elevated (peaks 1-2 hours after onset). Rarely used acutely, but helpful retrospectively to confirm anaphylaxis vs. other causes of shock.

Imaging Modalities & Findings

• None routinely indicated: Diagnosis is strictly clinical and requires immediate intervention without waiting for diagnostics.

• Uniphasic
  A single acute episode that resolves with treatment and does not return.
• Biphasic
  Recurrence of symptoms hours after apparent resolution, without further exposure to the trigger.

Second-Line & Adjunctive Therapy

Adjunctive therapies (never replace epinephrine): H1-antihistamines (Diphenhydramine 50 mg IV), H2-antihistamines (Famotidine 20 mg IV), Corticosteroids (Methylprednisolone 125 mg IV) to prevent biphasic reactions, and inhaled Albuterol for persistent wheezing.

Surgical & Procedural Management

Surgical airway (Cricothyroidotomy) or endotracheal intubation is required emergently if severe laryngeal edema prevents ventilation.

Recommended Lifestyle Changes

• Strict avoidance of identified trigger allergens.
• Wear medical alert jewelry detailing the allergy.

Patient Counseling & Advice

Train the patient and family extensively on how and when to use an epinephrine auto-injector. Emphasize that epinephrine should be used immediately at the first sign of anaphylaxis, and they must call 911 immediately after administration.

Follow-Up & Monitoring Schedule

Patients should be observed in the emergency department for 4-6 hours (or longer for severe cases) to monitor for a biphasic reaction. Referral to an allergist for formal testing and desensitization if applicable.

Preventive Strategies

Carry two epinephrine auto-injectors at all times. Venom immunotherapy (allergy shots) for insect sting anaphylaxis is highly effective in preventing future reactions.

Excellent if recognized early and treated promptly with epinephrine. Fatalities usually occur when epinephrine is delayed or not administered.