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