A 28-year-old woman presents to the emergency department with acute onset of urticaria, angioedema of the lips and tongue, and dyspnea 15 minutes after receiving intravenous penicillin G for pneumonia. Her blood pressure is 95/60 mmHg, heart rate 120/min, and respiratory rate 28/min. Skin examination shows widespread erythematous wheals. Which of the following best explains the immunological mechanism underlying this acute reaction?

Explanation

## Immunological Mechanism of Acute Anaphylaxis ### Type I Hypersensitivity Reaction **Key Point:** This patient presents with classic anaphylaxis — a Type I hypersensitivity reaction characterized by IgE-mediated mast cell and basophil degranulation occurring within minutes of antigen exposure. ### Pathophysiology 1. **Sensitization phase**: Previous exposure to penicillin (or cross-reactive β-lactam) leads to IgE synthesis and binding to high-affinity IgE receptors (FcεRI) on mast cells and basophils. 2. **Re-exposure and degranulation**: Upon re-exposure, penicillin acts as a hapten, cross-linking surface-bound IgE on mast cells. This triggers rapid degranulation within seconds to minutes. 3. **Mediator release**: - **Preformed mediators** (released immediately): Histamine, tryptase, heparin, chymase - **Newly synthesized mediators** (released over minutes): Leukotrienes (LTC₄, LTD₄, LTE₄), prostaglandins (PGD₂), platelet-activating factor (PAF) ### Clinical Manifestations Explained | Symptom | Mediator | Mechanism | |---------|----------|----------| | Urticaria & angioedema | Histamine | Increased vascular permeability, smooth muscle contraction | | Dyspnea | Leukotrienes, histamine | Bronchial smooth muscle constriction | | Hypotension | Histamine, PAF | Peripheral vasodilation, increased capillary permeability | | Tachycardia | Catecholamine response | Compensatory sympathetic activation | **High-Yield:** Tryptase is a serum marker of mast cell degranulation and can be measured within 15 minutes to 3 hours of symptom onset to confirm anaphylaxis retrospectively. **Clinical Pearl:** The rapid onset (15 minutes) and involvement of multiple organ systems (skin, respiratory, cardiovascular) are pathognomonic for Type I hypersensitivity. The presence of angioedema distinguishes this from other rash-causing conditions. ### Mnemonic for Type I Hypersensitivity Features **FAST** — **F**ast onset, **A**ntibody (IgE), **S**ensitization required, **T**wo exposures needed (or one if previously sensitized).