How do you perform skin testing for cephalexin allergy in a patient with a potential history of penicillin allergy?

Skin Testing for Cephalexin in Patients with Penicillin Allergy History

Skin testing to cephalexin has "no clear utility" in clinical practice and should not be performed routinely—instead, either avoid cephalexin entirely if the patient has anaphylactic penicillin allergy, or select a different cephalosporin with a dissimilar R1 side chain that can be given directly without any testing. 1

Critical Decision Point: Assess the Penicillin Allergy History

The management hinges entirely on whether the patient has a history of anaphylactic penicillin allergy versus a non-anaphylactic reaction:

If Anaphylactic Penicillin Allergy History:

• Avoid cephalexin entirely without any testing due to a 12.9% cross-reactivity rate, as cephalexin shares an identical R1 side chain with aminopenicillins (amoxicillin/ampicillin). 1, 2

• The cross-reactivity rate for aminocephalosporins like cephalexin in patients with proven penicillin allergy is 16.45% (95% CI: 11.07-23.75), making it a high-risk option. 1

• Instead, select a cephalosporin with a dissimilar R1 side chain (such as cefazolin, ceftriaxone, or cefepime) which can be administered by direct challenge or full therapeutic dose without any testing. 1, 2

If Non-Anaphylactic Penicillin Allergy History:

• A patient with a history of urticaria to cephalexin can receive amoxicillin without prior testing, and penicillin skin testing is not recommended unless the cephalosporin allergy history was anaphylaxis, angioedema, hypotension, or other severe IgE-mediated reactions. 3

• For patients with unverified penicillin allergy, the reaction rate to cephalosporins is less than 5%, making direct administration reasonable. 3

When Skin Testing Might Be Considered (Rare Circumstances)

Skin testing to cephalexin is only advisable in highly specific circumstances, such as:

• Patients with multiple documented drug allergies 1
• Patients with significant anxiety about receiving the medication 1
• Patients with a history of severe/recurrent reactions 1

Skin Testing Protocol (If Deemed Necessary):

If you proceed with skin testing despite the lack of clear utility, use a stepwise approach:

1. Epicutaneous/prick testing: 200 mg/mL 1
2. Intradermal testing: 2.0 mg/mL 1
3. Intradermal testing: 20 mg/mL 1

Important caveat: This protocol has limited validation, and the predictive value of cephalosporin skin testing remains unclear. 1, 4

Alternative Strategy: Penicillin Delabeling

If cephalexin is specifically needed in a patient with anaphylactic penicillin allergy, consider penicillin skin testing first to confirm the allergy, followed by an oral amoxicillin challenge to delabel the penicillin allergy. 1

• If penicillin skin testing is performed and negative, a drug challenge to the penicillin is still advised. 3

• This approach greatly simplifies all future beta-lactam administration recommendations. 3

Common Pitfalls to Avoid

• Do not perform routine skin testing in drug-naïve patients (those without prior cephalosporin allergy), as it adds unnecessary cost, delay, and patient anxiety without clinical benefit. 1

• Do not assume 10% cross-reactivity between penicillins and cephalosporins—modern evidence shows the actual rate is 1-2% for cephalosporins with dissimilar side chains. 2

• Do not confuse cephalexin with low-cross-reactivity cephalosporins like cefazolin, which has a cross-reactivity rate of less than 1% and can be safely administered to patients with anaphylactic penicillin allergy. 2

• Patients with positive penicillin skin tests have a 6% adverse reaction rate to cephalosporins compared to 0.7% in those with negative skin tests, reinforcing the importance of avoiding high-risk cephalosporins like cephalexin in confirmed penicillin allergy. 5