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Elective PCN Skin Testing vs.

PCN Skin Testing at Time of Need

Timothy J. Sullivan, M.D.


Elective Penicillin Skin Testing

 Skin testing with a full battery of penicillin G


reagents will detect nearly all penicillin G or V
allergic patients
– ~2% chance of urticaria within 48 hours in skin
test negative patients
– ~0.1% chance of anaphylaxis in skin test negative
patients
– No convincing evidence skin tests sensitize or re-
sensitization
Elective Skin Testing for IgE to
Sulfamethoxazole

 Skin testing with Sulfamethoxazoyl poly-


tyrosine can detect nearly all patients who
express IgE to sulfamethoxazole
 Reagent must be synthesized within ~1
month of use in a well equipped laboratory
 If you do not have the reagent, you can not
do the test
Skin Testing To Detect Penicillin Allergy
Sullivan et.al. 1981. JACI 68:171-180.

A study of 469 skin test positive patients

– Penicilloyl-Poly-L-Lysine positive 76%


– PPL +/or Pen G positive 93%
– Penicilloate alone positive 7%
Skin Test For Diagnosis of Penicillin Allergy
Ressler, Mendelson. 1987. Ann Allergy 59:167-170.

 Review including 7 studies in addition to ours


using full batteries of minor determinant
reagents
– Patients reacting only to minor determinant
antigens ranged from 13% to 35% with an
average of 25%
– Relying on PPL to detect IgE to penicillin would
be expected to miss ~25% of allergic patients
Elective Penicillin G Skin Testing

 Testing with PPL alone will miss ~25% of


allergic subjects
 Testing with PPL and Pen G will miss ~7%
 Testing with PPL and Pen G and PA will
detect nearly all the remainder who would
react to penicillin G or V
PCN Skin Tests in 740 Hx+ Patients
Relation to time since reaction

100

80

60
% Positive

40

20

0
0-6 Mos 6-12 Mos 1-5 Years 5-10 Years >10 Years

Time after allergic reaction to penicillin


Sullivan et. al. 1981. JACI 68:171-180
PCN Skin Tests
Relation to time since reaction

 Skin testing too early can result in false


negative results
 Patients skin test positive now may well be
skin test negative when a need for penicillin
arises sometime in the future. Another skin
test at the time of need would be needed to
prevent useless avoidance.
Penicillins

Pen G Ampicillin
Piperacillin

Pen V Amoxicillin Ticarcillin


“Penicillin Allergy”

 Early studies of skin testing to detect IgE to


penicillin:
– Penicillin G or V sensitization
– Penicillin G skin test reagents
– Penicillin G or V therapy
 2010 Penicillin Allergy
– Amoxicillin sensitization
– Penicillin G skin test reagents
– Amoxicillin therapy
Penicillin G vs. Amoxicillin

 Amoxicillin differs from


penicillin G by having a
charged free amino
group and a hydroxyl
group in the side chain Penicillin G
 Immune responses to
haptens formed from
these two parent
molecules do not
always cross react
Amoxicillin
IgE to Amoxicillin may not be detected
by Penicillin G reagents

 Studies of patients sensitized by amoxicillin, tested


with penicillin G and amoxicillin reagents, and
challenged with amoxicillin are sparse.
 In vitro assays of IgE specificity with specific
inhibition show AMX specific IgE can be present
alone or concurrent with crossreactive IgE (Antunez
et.al. 2006. Allergy 61:940-946. And Sullivan
unpublished data.)
 Full value of AMX skin tests to detect these patients
not yet clear.
Elective Penicillin G Skin Testing
Pitfalls

 Testing too early


 Original immunologic sin was amoxicillin and
the drug needed is amoxicillin
 Interval administration of cross reacting
drugs (e.g. Cephalexin, Cefaclor)
 Re-sensitization by a subsequent course of a
penicillin
Resensitization by Penicillin Therapy

 High dose 6 weeks of therapy for SBE or


osteomyelitis – 60% (6 of 10) re-sensitized
(Earl & Sullivan)
 Hx+, previously ST+, now ST-, treated: 22%
resensitized (Polmar)
 Liberal Hx+, ST-, treated: <1% re-sensitized,
5.7% with stringent Hx+ (Mendelson)
A&I Physicians & Penicillin Allergic Patients
Consultation or Technical Support

 Accurate diagnosis
 Treatment of conditions disposing to need for
antibiotics (e.g. allergic rhinitis)
 Use of alternative classes of medications.
 Updated drug exposure information
 Assessment of current drug allergy status
 Desensitization if needed
 Treating through reactions
Elective PCN Skin Testing vs.
PCN Skin Testing at Time of Need

 Elective
PCN skin testing can be an excellent
community or institutional resource
– Patient and Primary Physician knowledge
essential to effective use of the information
 Effective management of drug allergic
patients is best achieved by expert
consultation
 An A&I physician is more important than a
readily available test without context
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