A 28-year-old woman presents to the emergency department 20 minutes after eating peanuts at a restaurant. She complains of severe itching in her mouth and throat, followed by facial angioedema and stridor. On examination, her blood pressure is 88/54 mmHg, heart rate 118/min, and she has urticarial rash over her trunk. Serum tryptase level is elevated at 8.5 ng/mL (normal <1 ng/mL). Which of the following best explains the pathophysiology of her acute symptoms?

Explanation

## Pathophysiology of Anaphylaxis This patient presents with **anaphylaxis**, a Type I hypersensitivity reaction triggered by peanut allergen cross-linking IgE on mast cells and basophils. ### Mechanism of Type I Hypersensitivity **Key Point:** Type I hypersensitivity occurs in two phases: 1. **Immediate phase (minutes)**: IgE-mediated mast cell/basophil degranulation → release of preformed mediators (histamine, tryptase, heparin) 2. **Late phase (4–12 hours)**: Synthesis and release of newly formed mediators (leukotrienes, prostaglandins, cytokines) ### Clinical Features Explained | Feature | Mediator | Mechanism | |---------|----------|----------| | Angioedema, urticaria | Histamine | Increased vascular permeability | | Stridor, bronchospasm | Leukotrienes (LTC₄, LTD₄, LTE₄) | Smooth muscle contraction | | Hypotension | Histamine, tryptase, bradykinin | Vasodilation + fluid shift | | Elevated tryptase | Mast cell degranulation | Confirms mast cell activation | **High-Yield:** Serum tryptase is a marker of mast cell degranulation and is elevated within 15–60 minutes of anaphylaxis onset. Levels >11.4 ng/mL strongly support the diagnosis. **Clinical Pearl:** The rapid onset (20 minutes) and presence of hypotension, angioedema, and urticaria are pathognomonic for IgE-mediated anaphylaxis. Tryptase elevation confirms mast cell activation. **Mnemonic: MAST** — **M**ediators (histamine, tryptase), **A**ntigen-IgE cross-linking, **S**wift onset (minutes), **T**issue response (edema, bronchospasm) ### Why This Is Type I, Not Other Types ```mermaid flowchart TD A[Allergen exposure]:::outcome --> B{IgE present?}:::decision B -->|Yes| C[IgE cross-links FcεRI on mast cells]:::action C --> D[Degranulation within minutes]:::action D --> E[Preformed mediators released]:::action E --> F[Anaphylaxis: angioedema, hypotension, stridor]:::outcome B -->|No| G[Type III or IV reaction]:::outcome ``` **Key Point:** The **immediate onset** (20 min) rules out Type IV (24–72 hours). The **systemic symptoms** (hypotension, angioedema) rule out isolated Type II (cytotoxic) or Type III (immune complex) reactions, which typically present with localized or vasculitic manifestations.