A 28-year-old woman presents with acute onset dyspnea, urticaria, and angioedema 15 minutes after receiving intravenous penicillin. She has a history of severe reactions to cephalosporins. Which investigation is most appropriate to confirm the diagnosis of IgE-mediated hypersensitivity?

Explanation

## Diagnosis of IgE-Mediated Drug Hypersensitivity ### Clinical Context The patient presents with classic Type I hypersensitivity features: rapid onset (15 minutes), urticaria, angioedema, and respiratory symptoms following penicillin exposure. Confirmation requires demonstration of specific IgE antibodies. ### Investigation of Choice: Skin Prick Test **Key Point:** Skin prick testing (SPT) with penicillin determinants is the gold standard for diagnosing IgE-mediated penicillin allergy in non-acute settings. **High-Yield:** The test uses: - Penicillin G (major determinant) - Penicilloyl-polylysine (PPL) — major determinant - Minor determinants (penicilloate, penilloate) - Positive control (histamine) - Negative control (saline) **Clinical Pearl:** A wheal-and-flare reaction (≥3 mm above negative control) within 15–20 minutes indicates specific IgE binding to mast cells, confirming Type I hypersensitivity. ### Why SPT is Superior | Feature | Skin Prick Test | Serum Tryptase | Intradermal Test | Complement Fixation | |---------|---|---|---|---| | **Sensitivity** | 90–95% | 50–60% (only acute phase) | Higher but risk of anaphylaxis | Low | | **Specificity** | High | High but time-dependent | High | Very low for Type I | | **Safety** | Safe; minimal systemic absorption | Non-invasive | **Contraindicated in acute allergy** | Not diagnostic for IgE | | **Timing** | Can perform 4–6 weeks post-event | Must draw within 3 hours of onset | Dangerous in recent anaphylaxis | Not relevant | | **Standardization** | Standardized reagents available | Variable lab methods | Poorly standardized | Obsolete for allergy | ### Rationale for Each Option **Skin prick test (CORRECT):** - Directly detects IgE-mast cell interaction - Safe, rapid, reproducible - Can be performed weeks after acute event - Determinant testing (major + minor) maximizes sensitivity **Serum tryptase:** - Useful to confirm mast cell degranulation during acute anaphylaxis - Must be drawn within 3 hours of symptom onset (peak at 15–30 min) - Does NOT identify the causative allergen - Cannot be used retrospectively for diagnosis **Intradermal test:** - Contraindicated in patients with recent anaphylaxis due to risk of systemic reaction - Reserved for negative SPT when clinical suspicion remains high - Less standardized than SPT **Complement fixation test:** - Detects IgG or IgM antibodies, not IgE - Relevant for Type II or Type III hypersensitivity - Not diagnostic for immediate-type allergy **Mnemonic:** **SPT-SAFE** = Skin Prick Test, Specific, Allergen-determinant, Fast, Early (can do weeks later) [cite:Harrison 21e Ch 297]