How is penicillin allergy verification done?

Penicillin Allergy Test Verification Protocol

Penicillin allergy testing is performed through a structured process of skin testing followed by oral challenge in patients with negative skin tests, with the gold standard being a graded drug provocation test using the specific penicillin to which the patient previously reacted. 1

Initial Assessment

• History evaluation: Determine if testing is even necessary
  • Patients with histories inconsistent with allergy (headache, family history, isolated GI symptoms) do not require testing 1
  • Only 10-20% of patients reporting penicillin allergy are truly allergic when assessed by skin testing 2

Skin Testing Procedure

Preparation

• Ensure patient has not taken antihistamines recently:
  • No chlorpheniramine/terfenadine within 24 hours
  • No diphenhydramine/hydroxyzine within 4 days
  • No astemizole within 3 weeks 1

Testing Protocol

1. Epicutaneous (Prick) Tests:

   • Place duplicate drops of skin-test reagent on volar forearm
   • Pierce epidermis with 26-gauge needle without drawing blood
   • Positive result: wheal diameter ≥4 mm larger than negative control after 15 minutes 1

2. Intradermal Tests (if prick tests negative):

   • Inject 0.02 mL of reagent into volar forearm using 26/27-gauge needle
   • Positive result: wheal diameter >2 mm larger than initial wheal size and >2 mm larger than negative controls after 15 minutes 1

Testing Reagents

• Standard panel (when available):

  • Major determinant: Benzylpenicilloyl poly-L-lysine (Pre-Pen)
  • Minor determinant mixture (MDM)
  • Penicillin G 1

• Limited panel (when full panel unavailable):

  • Major determinant: Benzylpenicilloyl poly-L-lysine (Pre-Pen)
  • Penicillin G 1

• Controls:

  • Positive control: Histamine
  • Negative control: Saline 1

Risk Stratification

• High-risk patients (history of anaphylaxis, asthma, beta-blocker use):

  • Test with 100-fold dilutions before full-strength reagents
  • Perform in monitored setting with anaphylaxis treatment available 1

• Moderate-risk patients (non-anaphylactic immediate reactions within past year):

  • Test with 10-fold dilutions before full-strength reagents 1

Interpretation and Next Steps

• Skin test positive: Patient is allergic and should be desensitized if penicillin is needed 1

• Skin test negative with full panel: Patient can safely receive conventional penicillin therapy (negative predictive value >95%) 1

• Skin test negative with limited panel: Two approaches:

  1. Consider patient possibly allergic and proceed with desensitization
  2. Perform oral challenge with gradual dosing in monitored setting 1

Oral Challenge

• For patients with negative skin tests or low-risk histories
• Administer single treatment dose of amoxicillin under observation 1
• Monitor for reactions for at least 1 hour

Special Considerations

• Delayed hypersensitivity reactions: Standard skin testing primarily detects IgE-mediated reactions; delayed readings may be needed for non-immediate hypersensitivity reactions 1

• Declining sensitivity: Penicillin allergy may wane over time; approximately 90% of people with previous reactions eventually lose their sensitivity 1, 3

• Testing accuracy: Skin testing has superior diagnostic accuracy (sensitivity 30.7%, specificity 96.8%) compared to in vitro specific IgE testing (sensitivity 19.3%, specificity 97.4%) 1

Pitfalls and Caveats

• Skin testing without minor determinants may miss 3-10% of allergic patients 1
• False negatives can occur if patient has recently taken antihistamines 1
• Testing should only be performed by trained personnel with preparedness to treat anaphylaxis 1
• Penicillin allergy labels are frequently incorrect and lead to suboptimal antibiotic choices, increased healthcare costs, and potentially worse outcomes 1, 3

By following this systematic approach to penicillin allergy testing, clinicians can accurately identify truly allergic patients while safely "delabeling" the approximately 90% of patients with reported penicillin allergy who can actually tolerate these antibiotics.