The Role of Patch Testing in Evaluating Delayed Hypersensitivity Reactions to Medications

Abstract

Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life threatening. We review the literature on ideal patch testing technique for specific CADRs. Testing should be performed approximately 3 months after the resolution of the eruption using standard patch testing techniques. Commercially available patch test preparations are available for a minority of drugs, so in most cases, testing should be performed with the drug at various recommended concentrations and in different vehicles. Testing to all known excipients, such as dyes, vehicles and preservatives is also important. Immunosuppressive medications should be discontinued or down titrated to the lowest tolerable dose to decrease the risk of false negative reactions. We provide an overview of expert recommendations and extant evidence on the utility of patch testing for identifying the culprit drug in common CADRs and for specific drug or drug classes. Overall, there appears to be significant variability in the patch test positivity of different drugs, which is likely the result of factors intrinsic to the drug such as dermal absorption (as a function of lipophilicity and molecular size) and whether the drug itself or a downstream metabolite is implicated in the immune reaction. Drugs with high patch test positivity rates include beta-lactam antibiotics, aromatic anticonvulsants, phenytoin, and corticosteroids, among others. Patch testing positivity varies both as a function of the drug and type of CADR. The sum of the evidence suggests that patch testing in the setting of morbilliform eruptions, fixed drug eruption, acute generalized exanthematous pustulosis, and possibly also drug-induced hypersensitivity syndrome, photoallergic and eczematous reactions may be worthwhile, although utility of testing may vary on the specific drug in question for the eruption. It appears to be of limited utility and is not recommended in the setting of other complex CADR, such as SJS/TEN and leukocytoclastic vasculitis.

Fixed drug eruptions – the common and novel culprits since 2000

“…In general, the offending drug is diluted in petroleum or water at a concentration of 0.5-30 %, with readings made 48-96 hrs. after application [27]. A result is considered positive if previously involved skin reacts with marked erythema, oedema, vesicles, or bullae formation [4,8].…”

Tools to improve the diagnosis and management of T-cell mediated adverse drug reactions

“…Another advantage of this tool, compared to the IDT, is the possibility to use non-sterile and oral drug formulations. It is also interesting to note that the positivity of this tool seems to depend on the assessed drug as well as the reported reaction (108) performed following a negative PT. In the pediatric population, while the literature is very limited, the sensitivity seems to be lower compared to the adult population (94).…”

“…Another advantage of this tool, compared to the IDT, is the possibility to use non-sterile and oral drug formulations. It is also interesting to note that the positivity of this tool seems to depend on the assessed drug as well as the reported reaction ( 108 ). In the clinical setting, considering this low reported sensitivity, lack of a validated positive control and less than 100% negative predictive value, removal of the allergy label should not be performed following a negative PT.…”

Fixes Arzneimittelexanthem – häufige und neue Auslöser seit dem Jahr 2000

“…Sowohl der offene als auch der okklusive Epikutantest wurden beschrieben. Im Allgemeinen wird das auslösende Medikament in Mineralöl oder Wasser auf eine Konzentration von 0,5–30 % verdünnt und das Ergebnis 48–96 Stunden nach der Applikation ausgewertet [27]. Ein Ergebnis gilt als positiv, wenn die zuvor betroffene Haut mit der Bildung eines deutlichen Erythems, Ödems, Vesikeln oder Blasen reagiert [4, 8].…”