Elsevier

Clinics in Dermatology

Volume 28, Issue 3, May–June 2010, Pages 349-353
Clinics in Dermatology

The challenge of drug-rechallenge: Facts and controversies

https://doi.org/10.1016/j.clindermatol.2009.06.019Get rights and content

Abstract

The accurate identification of the culprit drug inducing a patient's cutaneous adverse drug reaction is important to avoid future adverse reactions and to provide safe alternative drugs. The assessment has to rely on the clinical signs, the time course, and response to treatment. Sometimes, additional diagnostic procedures are also needed. If diagnostic procedures such as in vivo skin testing and in vitro laboratory tests do not lead to conclusive results, confirmation of a presumptive diagnosis by a rechallenge test is often the only reliable way to establish a diagnosis. This procedure should be undertaken only with great caution and a compelling need, because a rechallenge test might cause severe or even fatal reactions. Contraindications and ethical considerations should be taken into account and an individual risk-benefit calculation must be performed in every case.

Section snippets

The clinical spectrum of drug eruptions

The clinical spectrum of drug eruptions is diverse. They are often called the big imitators, although the most common manifestation in 75% to 95% of all patients is a morbilliform eruption (exanthem). Drugs can also:

  • cause hair and nail changes, affect the mucous membranes, or cause itching without outward skin changes12;

  • mimic infective or idiopathic diseases;

  • initiate dermatologic diseases, for example, psoriasis (β-blockers, antimalarials, and lithium), pemphigus (D-penicillamine, captopril),

Identifying the culprit drug

Accurate identification of the responsible agent is important for future treatments and to avoid labeling the patient as being “allergic” for life without good reason. The diagnosis of drug eruption is mainly based on a constellation of features, including a precise characterization of the reaction type, a complete medical history, a through physical examination, and additional diagnostic tests. Because none of the single tests available has a sufficiently good sensitivity and because there is

The steps to diagnosis

First, a precise characterization of the reaction type should be established. Based on the primary lesion, four categories are described:

  • Exanthematous

  • Urticarial

  • Blistering

  • Pustular14

To evaluate the role of drugs when an eruption is suspected, the medical history should include a careful analysis of the patient's drug exposure. A complete list of medications should include prescription and over-the-counter medications, products that may not be thought of as medicines, such as herbal or traditional

Dechallenge and rechallenge tests

An important forward step toward identifying the offending drug is the dechallenge (withdrawal) and rechallenge test. This is one of the standard means of assessing ADRs. It is important to monitor the clinical course of the reaction after drug withdrawal, because resolution of the reaction during a reasonable time frame after the drug is discontinued may support a drug cause. The rechallenge test, also called drug provocation test, is restarting the intake of the suspected drug while the

Interpretation of test results and consequences

A withdrawal test is not always accurate because morbilliform eruptions may persist long after the culprit drug has been stopped. Other possibilities that cause transient eruptions, such as infective diseases, should also be considered.

The predictive value of the rechallenge test mainly depends on the type and mechanism of reaction and the drug involved. For example, urticarial reactions to penicillin therapy are frequently reproducible, whereas morbilliform eruptions after ampicillin are not,

Conclusions

Drug eruptions are not simply drug allergy but result from variations in drug metabolism, immune status, coexistent viral disease, and the inherent chemical structure and dosage of the medication. Timing, the pattern of illness, the results of investigations, and rechallenge can help to attribute causality to a suspected adverse drug reaction.

A rechallenge test should be performed only if the risk-benefit ratio is acceptable: the drug must be important for the individual patient, the condition

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    Affiliated to The School of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem, Israel.

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