How Should Dermatologists Confront Suspected Drug Allergies?

More than 20% of the population is suspected to have a penicillin allergy, yet less than 5% have this allergy. Because a recorded “penicillin allergy” entails altered antibiotic management, risk for infection, and antibiotic resistance, appropriate testing should be carried out to confirm or rule out the diagnosis. In a more general sense, for all drugs, checking for and categorizing a suspected allergy allows physicians to draw up a management plan according to the importance of the molecule for treating the disease in question. Depending on the assessment of this risk–benefit ratio, an alternative molecule or a structured reintroduction of the offending molecule can be considered. This approach was outlined by Angèle Soria, MD, PhD, a dermatologist and allergist at Tenon Hospital in Paris, at the French Dermatology Society’s annual conference in Paris.

A Negative Test

To prove an allergy, the first stage of the approach is testing: skin tests, prick tests, or delayed reading intradermal tests, depending on the type of drug allergy.

In patients with immediate hypersensitivity reactions or anaphylaxis, which are immunoglobulin E-mediated reactions, symptoms appear within 2 hours of taking the drug and resolve quickly (in under 24 hours) once the drug is stopped. Investigation of these allergies involves prick tests or intradermal tests (for injectable drugs), with reactions read within 20 minutes.

In delayed hypersensitivity reactions or drug eruptions, which involve specific T lymphocytes, symptoms don’t appear until after 2 hours post testing and last for several days before resolving. Such cases involve patch testing, delayed reading intradermal tests, or repeated open application tests, for which reactions are not read until 2 to 7 days after testing.

However, these tests are imperfect and don’t always result in an allergy being proven or ruled out. In addition, although a positive result confirms a suspected allergy, a negative result doesn’t rule it out entirely.

Substitution or Desensitization

The second stage of the approach is to evaluate the risk–benefit ratio of the molecule and the existence of alternatives. If the drug is indispensable, then stratification of the risk and reaction will help physicians determine which protocol to implement. In the hospital, one can replace the molecule with one from the same family that is as chemically far from it as possible. For example, the rate of cross-reactivity with penicillin is less than 2% for certain group A cephalosporins but 25% to 35% for aminocephalosporins.

When the molecule cannot be avoided and no alternatives exist (for example, in the last line of chemotherapy treatment), a hospital-based or even intensive-care-based desensitization protocol should be discussed. Such a procedure involves the administration of gradually increasing doses to induce immune tolerance. “This type of protocol is more effective for cases of anaphylaxis than for drug eruptions,” said Soria.

About Penicillin

The PEN-FAST penicillin allergy clinical decision rule is a five-point scoring system enabling point-of-care risk assessment of patient-reported penicillin allergies. It requires the following three clinical criteria: time (5 years or less) from penicillin allergy episode (two points), phenotype (anaphylaxis, angioedema, or severe cutaneous reaction; two points), and treatment required for penicillin allergy episode (one point). A score below three out of five indicates a risk of having a penicillin allergy of under 5%.

“This test has mainly been validated using immediate hypersensitivity reactions and is less suitable for drug eruptions,” said Soria. Hence, maculopapular rashes, the most common drug eruption seen with aminopenicillins, evade the allergy risk tool. “We recently published a new PEN-FAST+ score that integrates these delayed hypersensitivity reactions,” she said. It adds the following two further criteria: a skin rash lasting > 7 days and a skin rash occurring in the hour after taking the drug.

In children, a suspected delayed hypersensitivity reaction to a penicillin-based drug presenting with a nonserious exanthema (small area, short-lasting, no extracutaneous symptoms) and a negative skin test can be palliated using a challenge test in a hospital setting to best investigate its allergic origin.

“All doctors can contraindicate a medicinal product,” Soria concluded. Categorizing an allergy or even delabeling patients erroneously labeled as penicillin-allergic can give them a better chance at fighting infections.

This article was translated from Univadis France, which is part of the Medscape professional network.