Patch Testing in the Diagnosis of Drug Reactions

Adverse drug reactions are not uncommon, especially in today’s age of modern medicine in which patients are often managed with multiple medications. Cutaneous adverse drug reactions (CADRs) (Table 1) are the most common type of adverse drug reaction, occurring in 2% to 3% of hospitalized patients and in 2% of patients referred for outpatient dermatologic evaluation.1 While the majority of these reactions are mild and self-limited, approximately 1 in 1000 hospitalized patients experiences a severe cutaneous adverse reaction (SCAR), such as drug rash with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome, acute generalized exanthematous pustulosis (AGEP), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).2 

CADRs should be in the clinical differential for new onset dermatitis, and often the diagnosis can be made clinically or with histologic support. That said, for patients taking multiple medications, determining the culprit medication underlying the CADR can prove a challenge that is worth undertaking, as prompt recognition of CADRs at the early stages of presentation and subsequent withdrawal of the offending agent can prevent progression with significant clinical long-term sequelae and/or relapse of the reaction. 

table 1

For certain CADRs, targeted cutaneous testing can be a helpful adjunct in determining the underlying causative medication. The methodology of cutaneous testing rests largely on the immunopathogenesis underlying the CADR: In cases of immediate (type I), IgE-mediated CADRs, such as urticaria/angioedema, rhinitis, conjunctivitis, bronchitis, and anaphylaxis, skin prick testing (with or without intradermal testing) is most commonly employed. In contrast, for nonimmediate, delayed (type IV) CADRs (reactions that typically manifest 48 hours or up to 1 week after a medication is last taken), including fixed drug eruptions, maculopapular rashes, and generalized eczema, patch testing can be used.3,4 In addition to the type of CADR and its underlying immunopathogenesis, the utility of patch testing also relies on the class and preparation of the suspected drug and the vehicle used in testing.4 

This article reviews the clinical evaluation of CADRs and the utility of patch testing in diagnosing delayed-type CADRs based on European guidelines, discusses patients who may benefit from patch testing, and summarizes the patch testing protocol in an effort to increase clinicians’ familiarity with this diagnostic tool.

Clinical Evaluation

Patient demographics, medical history, personal and/or family history of drug reactions, physical exam findings, and extent of the CADR should be gathered in evaluation of a CADR. All medications taken within the last 3 to 4 weeks prior to the development of the CADR should be documented in a timeline fashion. The type of CADR should be classified (as in Table 1) when possible; histologic examination based on skin biopsy obtained during the initial drug reaction may be helpful in this characterization.5

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