The challenge of drug-rechallenge: Facts and controversies
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:
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cause hair and nail changes, affect the mucous membranes, or cause itching without outward skin changes12;
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mimic infective or idiopathic diseases;
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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:
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Exanthematous
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Urticarial
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Blistering
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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.