A 28-year-old woman presents to the emergency department with acute onset of urticaria, angioedema of the lips and tongue, and stridor 15 minutes after receiving an intravenous injection of penicillin for a presumed urinary tract infection. Her blood pressure is 88/54 mmHg, heart rate 118/min, and respiratory rate 24/min. She reports a history of similar reaction to amoxicillin 2 years ago. Which of the following best explains the pathophysiological mechanism of this reaction?

Explanation

## Mechanism of Type I Hypersensitivity This patient presents with classic features of **Type I (immediate) hypersensitivity** to penicillin, manifesting within 15 minutes of exposure. ### Clinical Features Present - **Urticaria and angioedema** — mast cell degranulation in skin and mucosa - **Stridor and respiratory compromise** — laryngeal edema from histamine release - **Hypotension and tachycardia** — systemic anaphylaxis with vasodilation - **Rapid onset** — within 15 minutes (pathognomonic for Type I) - **Prior sensitization** — previous amoxicillin reaction confirms IgE priming ### Pathophysiology **Key Point:** Type I hypersensitivity is **IgE-mediated** and occurs in two phases: 1. **Sensitization phase** (prior exposure): - Penicillin acts as a hapten, binding to carrier proteins - Th2 cells promote B cell differentiation into plasma cells - IgE antibodies bind to high-affinity receptors (FcεRI) on mast cells and basophils 2. **Effector phase** (re-exposure): - Penicillin-hapten cross-links surface-bound IgE - Triggers mast cell and basophil degranulation - Release of **preformed mediators**: histamine, tryptase, heparin, chymase - Release of **newly synthesized mediators**: leukotrienes (LTC₄, LTD₄, LTE₄), prostaglandins, PAF ### Mediator Effects | Mediator | Effect | |----------|--------| | **Histamine** | Vasodilation, increased vascular permeability, bronchoconstriction, urticaria | | **Tryptase** | Marker of mast cell activation; measured in serum during acute reaction | | **Leukotrienes** | Potent bronchoconstriction; 1000× more potent than histamine | | **PAF** | Platelet aggregation, hypotension, shock | **High-Yield:** Anaphylaxis is the most severe form of Type I hypersensitivity and is a **medical emergency** requiring immediate IM epinephrine (0.3–0.5 mg of 1:1000 solution). **Clinical Pearl:** The presence of a prior reaction to a related β-lactam (amoxicillin) and rapid onset of systemic symptoms makes IgE-mediated anaphylaxis the diagnosis. Serum tryptase levels drawn during the acute phase (within 15 minutes to 3 hours) would be elevated, confirming mast cell degranulation. ### Why Not Other Types? - **Type II (cytotoxic)**: Develops over days to weeks; presents with hemolytic anemia or thrombocytopenia, not immediate anaphylaxis - **Type III (immune complex)**: Occurs 7–10 days after exposure; causes serum sickness with fever, arthralgia, and lymphadenopathy - **Type IV (delayed-type)**: T cell–mediated; occurs 24–72 hours after exposure; presents with contact dermatitis or drug rash, not anaphylaxis