Fixed drug eruption

In fixed drug eruptions (FDE), the lesions develop 1 to 2 weeks after a first exposure. With subsequent exposures, they appear within 24 hours. Clinically, one or a few, round, sharply demarcated erythematous and edematous plaques are seen (Fig. 22.10A), sometimes with a dusky, violaceous hue, central blister or detached epidermis (Fig. 22.10B). The lesions can be found anywhere on the body, but favor the lips, face, hands, feet and genitalia. An erosion may develop centrally (Fig. 22.10C,D) and the lesions progressively fade over several days, often leaving a residual postinflammatory brown pigmentation (Fig. 22.10E). Upon readministration of the causative drug, the lesions recur at exactly the same sites. With each recurrence, additional sites of involvement may appear or the number of lesions may remain constant. The presence of numerous lesions is referred to as generalized FDE, and it may be difficult to distinguish from erythema multiforme or SJS (when the oral mucosa is also involved).

In the non-pigmenting variant of FDE, the erythematous edematous plaques are characteristically quite large in diameter (>10 cm) and heal with no residua. They are often seen in the girdle region. Although pseudoephedrine is the drug most commonly associated with this particular variant of FDE, it has been reported with NSAIDs, betahistine,

cimetidine, acetaminophen and, in the original description, tetrahydrozoline in eyedrops. Linear FDE is a rare variant and could be confused with linear lichen planus. Histopathology reveals a superficial and deep interstitial and perivascular infiltrate in the dermis, composed of lymphocytes, eosinophils and sometimes neutrophils. There may be necrotic keratinocytes in the epidermis. Dermal melanophages are often the only histologic finding in non-inflammatory lesions. The drugs most frequently associated with FDE are sulfonamides, NSAIDs (in particular, phenazone derivatives), barbiturates, tetracyclines and carbamazepine[40,41]. Phenolphthaleininduced FDE is seen less commonly nowadays because this diphenylmethane derivative has been removed from a number of laxative preparations. In a recent study of 64 patients from Turkey, where the diagnosis of FDE was established via oral provocation, trimethoprim sulfamethoxazole was the most common offender, accounting for 75% of the cases. Less commonly, naproxen (12.5%), dipyrone (9.5%), dimenhydrinate (1.5%) and acetaminophen (1.5%) were the responsible drug. Sometimes, the inducing drug can be readministered without exacerbation, and there may be a refractory period after the occurrence of a fixed eruption. Patch testing in a previously involved site may be useful with several drugs, such as carbamazepine. When there is a single lesion, the differential diagnosis includes a spider bite or exaggerated arthropod bite reaction, and when there are many lesions, erythema multiforme or SJS. On the genitalia, herpes simplex viral infections are oftentimes considered and a periungual lesion can be mistaken for paronychia. It is not unusual for the patient to have been treated in the past for presumed soft tissue bacterial infections, especially in the case of the nonpigmenting variant.