Protocol for delayed penicillin and cephalosporin skin testing
Reasons:
1. Testing for delayed type hypersensitivity reactions currently can be preformed via delayed
intradermal reads (ID)[1] and/or patch testing (PT)[2-4].
2. Higher positivity with PT is seen in patients with erythroderma, Acute Generalized
Exanthematous Pustulosis (AGEP), Drug Rash with Eosinophilia Systemic Symptoms
(DRESS), fixed drug eruption and systemic contact dermatitis from drugs.[2]
a. Barbaud et al[5] performed the largest multicenter prospective study looking at the
usefulness and safety of patch tests in severe cutaneous adverse drug reactions
(SCARs). Among the 72 patients with a history of DRESS syndrome, 46 cases were PT
positive (64%). In patients with AGEP, 26 out of 45 patch tests were positive (58%).
b. In a large study of 826 patients[6] that were PT for suspected systemic drug allergy
(95% with a positive exanthema history), a positive PT reaction to one or more drugs
was seen in 89 of 826 (10.8%). Beta-lactams tested positive in 3.9% (39 of 1,008),
sulfonamides in 2.9% (15 of 518) and clindamycin in 19% (12 of 63). There were no
positive reactions in any of the tests to macrolides, tetracyclines and quinolones
tested.
c. Recommendation: Drug PT appears mostly safe with very few episodes of systemic
reaction and may be helpful in certain severe cutaneous drug eruptions. In light of
limited diagnostic tools, drug PT may be an option. However, due to lack of both
standardized concentrations for testing and availability of commercial tests as well as
a need for familiarity with PT, its clinical use may be limited for the practicing
allergist/immunologist.
3. Delayed ID testing appears to pick up more positive reactions than PT.
a. Romano et al.[7] reported on PT and delayed ID reading on patients with
maculopapular or urticarial reactions to cephalosporins. Three subjects
were positive to both PT and ID, and another two patients were positive only to ID
testing.
Recommendation: Although not challenging to perform in patients who are already
undergoing evaluation for immediate type allergy and improved sensitivity vs. patch
testing, the utility of delayed intradermal testing (which is frequently negative) as
opposed to proceeding directly to oral challenge is not well understood.
Methods:
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1. Patch Testing
2. Intradermal Testing with Delayed Reads
a. Volume to inject (0.02-0.05ml) to raise bleb of 3 mm [8]
b. When to read
i. 20-30 minutes [3]
ii. Delayed read of 24-72 hours, possibly day 7 [3-4]
iii. Positive test showing infiltration at the site
Supplies:
1. For patch testing
a. Penicillin
i. Ampicillin 5% in petrolatum is commercially available (www.allergeaze.com)
ii. Β Lactams usually tested in Petrolatum at 5-10% concentration
1. Pen G 1-5% Petrolatum (no consensus-various concentrations used)
Note: Not available commercially
b. Cephalosporin
i. 5-20% in petrolatum or pure; 0.5% aqueous (no consensus-various
concentrations used) Note: Not available cmmercially
ii. When to perform [3-4]
a. European Network Drug Allergy guidelines: wait 3 weeks to
3 months after healing of the drug eruption
b. European Society of Contact Dermatitis guidelines: wait 6
weeks to 6 months after complete healing of the drug
eruption
iii. When to read patch test [3-4]
a. ENDA: Day 2 and Day 3 or 4
b. ESCD: 20 minutes, Day 2, Day 3 or 4 and Day 7 if Day 4 is
negative
iv. How to read patch test [3-4]
a. ENDA- European Environmental Contact Dermatitis
Research Group Criteria
b. ESCD- International Contact Dermatitis Research Group
Criteria
c. Patch test should be removed 48 hours after placement,
with an initial reading at this time, and again 72-96 hours
after placement. Patch test results should be evaluated 30
minutes after removal of the test materials to allow for the
irritation from the adhesive material to subside. The
standardized grading system should be used at both the 48and 72-96-hour reading.
d. Please see accompanying document “ Reading and
Interpretation of Drug Allergy Patch Testing”
2. For intradermal Reading
i. Same agents used for intradermal immediate hypersensitivity skin testing
read at 24-72 hours later
ii. How to read intradermal:
2
1. ESCD recommends measuring diameter of the papule (9)
2. ENDA recommends measuring diameter of infiltrative erythema/
erythematous swelling (9)
Cautions/Tips:
1. Patients should withhold oral immunosuppressives (prednisone) for at least 3-4 weeks prior
to patch testing and topical immunosuppressives to the back for at least 1-2 weeks prior to
patch testing.
2. Reactivation of drug eruptions has been reported to occur with drug PT and intradermal
drug testing. Risk and benefit ratios should be considered before performing patch or
intradermal skin testing in patients with severe cutaneous drug eruptions.
3. Contraindications* to intradermal testing based on ESCD: Severe cutaneous drug eruptions,
leukocytoclastic vasculitis. ENDA recommends patch testing first then intradermal testing if
negative.
4. Avoid performing PT if patient has sunburn on back and during pregnancy or acute illness
with fever.
5. In drug patch testing for fixed drug eruptions, it is recommended to perform PT on lesional
skin vs. non-lesional skin to reduce false negatives.
6. At least two vehicles should be used to prepare drug PT (petrolatum and water) to increase
the likelihood of penetration of the drug into the epidermis.
1.
2.
3.
4.
5.
6.
7.
8.
9.
Solensky, R. and D.A. Khan, Evaluation of antibiotic allergy: the role of skin tests and drug
challenges. Curr Allergy Asthma Rep, 2014. 14(9): p. 459.
Aquino, M.R., J. Sher, and L. Fonacier, Patch testing for drugs. Dermatitis, 2013. 24(5): p. 205-14.
Barbaud, A., et al., Guidelines for performing skin tests with drugs in the investigation of
cutaneous adverse drug reactions. Contact Dermatitis, 2001. 45(6): p. 321-8.
Brockow, K., et al., General considerations for skin test procedures in the diagnosis of drug
hypersensitivity. Allergy, 2002. 57(1): p. 45-51.
Barbaud, A., et al., A multicenter study to determine the value and safety of drug patch tests for
the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol, 2012.
Lammintausta, K. and O. Kortekangas-Savolainen, The usefulness of skin tests to prove drug
hypersensitivity. Br J Dermatol, 2005. 152(5): p. 968-74.
Romano, A., et al., Diagnosing nonimmediate reactions to cephalosporins. J Allergy Clin
Immunol, 2012. 129(4): p. 1166-9.
Barbaud, A., Skin testing in delayed reactions to drugs. Immunol Allergy Clin North Am, 2009.
29(3): p. 517-35.
Romano, A., M. Viola, et al. (2008). "Patch testing in non-immediate drug eruptions." Allergy
Asthma Clin Immunol 4(2): 66-74.
From the ACAAI 2015 Drug Allergy and Anaphylaxis Committee
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