A 28-year-old woman presents to the emergency department with acute onset of facial angioedema, urticaria, and dyspnea 15 minutes after receiving intravenous penicillin for a urinary tract infection. She reports a history of similar reactions to cephalosporins. On examination, she is anxious, with wheezing audible on auscultation, blood pressure 88/54 mmHg, and heart rate 118/min. Serum tryptase level is markedly elevated. Which of the following best describes the pathophysiologic mechanism underlying this reaction?

Explanation

## Pathophysiologic Mechanism This patient presents with **anaphylaxis**, a Type I hypersensitivity reaction characterized by rapid onset (within minutes) of systemic symptoms including angioedema, urticaria, bronchospasm, and cardiovascular collapse. ### Mechanism of Type I Hypersensitivity **Key Point:** Type I hypersensitivity is IgE-mediated and involves two phases: 1. **Sensitization phase** — Initial exposure to antigen (penicillin) leads to Th2 cell activation and B cell production of IgE antibodies, which bind to high-affinity IgE receptors (FcεRI) on mast cells and basophils. 2. **Re-exposure phase** — Cross-linking of IgE on mast cell/basophil surface by antigen triggers rapid degranulation with release of: - **Preformed mediators** (within seconds): histamine, tryptase, heparin, chymase - **Newly synthesized mediators** (within minutes): leukotrienes (LTC4, LTD4, LTE4), prostaglandins (PGD2), thromboxane A2, platelet-activating factor (PAF) ### Clinical Correlation **Clinical Pearl:** The markedly elevated serum tryptase is diagnostic for mast cell degranulation and confirms Type I hypersensitivity. Tryptase peaks at 15–30 minutes post-onset and is the most specific marker for anaphylaxis. **High-Yield:** The rapid onset (15 minutes), cross-reactivity between penicillins and cephalosporins (due to β-lactam ring homology), and presence of systemic symptoms (cutaneous, respiratory, cardiovascular, GI) are hallmark features of IgE-mediated anaphylaxis. ### Why This Mechanism Fits - **Timing**: IgE-mediated reactions occur within minutes (Type I) vs. hours to days (Type III/IV) - **Symptoms**: Angioedema, urticaria, and bronchospasm result from histamine and leukotriene effects on endothelial permeability and smooth muscle - **Hemodynamic collapse**: PAF and other mediators cause vasodilation and increased vascular permeability - **Tryptase elevation**: Specific marker of mast cell/basophil degranulation **Mnemonic:** **RASH** = Rapid onset, Angioedema/urticaria, Systemic (multi-organ), Histamine/mediators → Type I hypersensitivity