A 28-year-old woman presents to the emergency department 15 minutes after eating peanuts at a restaurant. She develops acute onset of urticaria, angioedema of the lips and tongue, wheezing, and hypotension (BP 88/54 mmHg). She has a history of similar reactions to tree nuts. On examination, she is anxious, has diffuse erythema, and stridor is audible. Which of the following best explains the pathophysiology of her acute symptoms?

Explanation

## Pathophysiology of Anaphylaxis **Key Point:** The clinical presentation — acute onset (minutes), urticaria, angioedema, bronchospasm, and cardiovascular collapse — is pathognomonic for **Type I hypersensitivity (immediate hypersensitivity)**. ### Mechanism In a sensitized individual: 1. **Antigen recognition:** Peanut allergen (e.g., Ara h 1, Ara h 2) cross-links IgE bound to high-affinity Fc receptors (FcεRI) on mast cells and basophils. 2. **Degranulation:** Within seconds to minutes, calcium influx triggers exocytosis of preformed mediators: - **Histamine** → vasodilation, increased vascular permeability, bronchoconstriction, pruritus - **Tryptase** → protease activity, further tissue damage - **Heparin** → anticoagulation 3. **De novo synthesis:** Arachidonic acid metabolites (leukotrienes C₄, D₄, E₄; prostaglandins) amplify bronchospasm and vasodilation. ### Clinical Correlation **High-Yield:** The **biphasic response** can occur: initial symptoms resolve, then recur 4–12 hours later due to newly synthesized mediators and recruitment of eosinophils and neutrophils. This patient requires observation and repeat epinephrine dosing if symptoms recur. **Clinical Pearl:** Anaphylaxis is a **clinical diagnosis** — do not wait for serum tryptase or IgE levels. Immediate IM epinephrine (0.3–0.5 mg of 1:1000 solution) is the first-line treatment; IV access, antihistamines (H₁ and H₂ blockers), and corticosteroids are adjunctive. ### Why This Is Type I, Not Type III or IV | Feature | Type I | Type III | Type IV | |---------|--------|----------|--------| | **Onset** | Seconds–minutes | 3–8 hours | 24–72 hours | | **Mediator** | Preformed (histamine, tryptase) | Immune complexes + complement | T cell cytokines | | **Cells** | Mast cells, basophils | Neutrophils, macrophages | CD8+ T cells, macrophages | | **Example** | Anaphylaxis, urticaria | Serum sickness, vasculitis | Contact dermatitis, TB skin test | **Mnemonic:** **ITCH** — **I**mmunoglobulin E, **T**ype I, **C**ytotoxic mediators (histamine), **H**ypersensitivity. Immediate onset, IgE-mediated, histamine-driven.