Fixed Drug Eruptions FDEs usually appear as solitary, erythematous, bright red or dusky red macules that may

evolve into an edematous plaque; bullous-type lesions may be present. FOEs are most commonly found on the genitalia and in the perianal area, although they can occur anywhere on the skin surface (Fig. 40-5). Some patients may complain of burning or stinging, and others may have fever, malaise, and abdominal symptoms. FDE can develop from 30 minutes to 8 to 16 hours after ingestion of the medication. After the initial acute phase lasting days to weeks, residual grayish or slatecolored hyperpigmentation develops. On rechallenge, not only do the lesions recur in the same location, but also new Iesions often appear. More than 100 drugs have been impUcatedin causing FDEs, including ibuprofen, sulfonamides, naproxen, and tetracyclines. A haplotype linkage in trimethoprim-sulfamethoxazole- induced FDE has been documented. 43"A challenge or provocation test with the suspected drug may be useful in establishing the diagnosis. Patch testing at the site of a previous lesion yields a positive response in up to 43 percent of patients. Results of prick and intradermal skin tests may be positive in 24 percent and 67 percent of patients, respectively.45 Fitzpatrick hal 397-398

Fixed Drug Reactions Fixed drug reactions are common. Fixed drug erupttons are so named because they recur at the same site wlth each exposure to the med~cation. In most pattents, six or fewer lesions occur, frequently only one. Uncommonly, fixed eruptions may be multifocal with numerous lesions. They may present anywhere on the body, but half occur on the oral and genital mucosa. Fixed eruptions represent 2% of all genital ulcers evaluated at clinics for sexually-transmitted diseases (Fig. 6-37), and are not infrequent in young boys. Clinically, a fixed eruption begins as a red patch that soon evolves to an iris or target lesion identical to erythema multlfome, and may eventually bltster and erode. Lesions of

the genital and oral mucosa usually present as erosions. Most lestons are 1 to several cm in diameter, but larger plaques may occur, resembling cellulitts. Charactenstically, prolonged or permanent postinflammatory hyperp~gmentahon results, although a nonpigmenting variant of a fixed drug eruphon is recognized. With repeated or continued ingestton of the offending medication, new lesions may be added, sometimes eventuating in a clinical picture similar to druginduced erythema multiforme major. Histologically, an interface dermatitis occurs with intraepidermal and subepidermal vesicle formation, necrosis of keratinocytes, and a mixed superficial and deep infiltrate of neutrophils, eosinophils, and mononuclear cells. Pigment incontinence is usually marked, correlating with the pigmentation resulting from fixed drug eruptions. As biopsies are generally performed during the acute stage of a recurrence, the stratum corneum is normal. Papillaly dermal fibrosis and deep perivascular pigment incontinence are commonly present fmm prior episodes. This contrast between a normal stratum corneum (suggesting an acute process) and chronic dermal changes is virtually pathognomonic of fixed drug eruption. I Medications inducing fixed drug eruptions are usually those taken intermittently. Many of the NSAIDs, especially pyrazolone derivatives, paracetamol, naproxen, oxicams, and mefenamic acid cause fixed drug eruption, with a special predilection for the lips. Sulfonamides, trimethoprim, or the combination are now responsible for the majority of genital fixed drug eruptions. Barbiturates, tetracyclines, phenolphthalein (in laxatives), acetaminophen, ceterizine, celecoxib, dextmmetbophan, hydroxyzine, lamotrigine, phenylpropanolamine,

erythromycin, and Chinese and Japanese herbs are other possible causes.The risk of developing a fixed drug eruption has been linked to HLA-B22. Patch tests with various concentrations of the offending medication can reproduce I the lesion on affected but not unaffected skin.Tape stripping the skin before applying the suspected medication in various vehicles may increase the likelihood of a positive patch test.This technique appears to be most useful in pyrazolone derivative-related reactions that are reproduced in 85% or more of cases. Occasionally, fixed drug reactions do not result in longlasting hyperpigmentation. The so-called nonpigmenting fixed drug eruption is distinctive. It is characterized by large, tender, often symmetrical erythematous plaques that resolve completely within weeks, only to recur on reingestion of the offending drug (Fig. 6-38). Pseudoepltedrine hydrochloride is by far the most common culprit.?he baboon syndrome, where the buttocks, groin, and axilla are preferentiaIly involved, is I considered a nonpigmenting fured drug eruption by some. Lesions of a fixed drug eruption contain intraepidermal CD8tT-cells with the phenotypic markers of effector memory T-cells. These skin-residentT-cells rapidly pmduce IFN-y on exposure to the offending medication. By Andrews disease of the skin hal 138