Test reagents:
(1) major penicillin determinant = benzylpenicilloyl polylysine (BPP) or penicilloyl-polylysine (PPL)
(2) minor penicillin determinants (see next)
(3) positive control = histamine solution (1.8 mg/mL for prick test; 0.1 mg/mL for intradermal injection)
(4) negative control = normal saline
Minor determinant mixture (MDM) may not be commercially available in the US. It can be approximated by a mixture of the following prepared in phosphate buffer:
(1) benzylpenicillin (0.01 M)
(2) benzylpenicilloate (alkaline hydrolysis product of benzylpenicillin, 0.01 M)
(3) benzylpenilloate (acid hydrolysis product of benzylpenicillin, 0.01 M)
Testing is done in 2 steps:
(1) prick or scratch test. If a prick or scratch test is negative, then proceed to intradermal testing.
(2) intradermal injection of small amount (0.02 to 0.03 mL) using a tuberculin syringe and a 25 or 27 gauge needle
The site of administration is assessed in 15-20 minutes after each test.
Criteria for a positive reaction (varies with different authors):
(1) wheal and flare reaction larger than negative control (Arroliga et al)
(2) wheal reaction >= 4 mm, plus erythema in a light-skinned patient
(3) wheal reaction >= 5 mm
(4) wheal reaction twice the size of the negative control
(5) for a prick test, erythema > 5 mm or wheal > 3 mm
where:
• As indicated by Gadded et al, erythema may be difficult to assess in dark-skinned patients.
Criteria for a valid test:
(1) positive control produces a wheal >= 4 mm in diameter
Criteria for an invalid test:
(1) negative control reactive
(2) positive control negative (may be due to concurrent antihistamine therapy)
Interpretation:
• A patient with a history of IgE-mediated allergy to penicillin and a negative skin test can be safely treated with penicillin, since a negative skin test has a negative predictive value > 99% (Forrest et al).
• A negative skin test does not have predictive value for a non-IgE-mediated allergic reaction.
