Fixed Drug Eruptions Clinical Presentation

Updated: Oct 09, 2020
  • Author: David F Butler, MD; Chief Editor: Dirk M Elston, MD  more...
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The initial eruption is often solitary and frequently located on the lip or genitalia. Rarely, the eruption may be intraoral. Other common locations of the initial lesion are the hip, lower back/sacrum, or proximal extremity. With the initial fixed drug eruption attack, a delay of up to 2 weeks may occur from the initial exposure to the drug to the development of the skin lesion. [47] Skin lesions develop over a period of hours but require days to become necrotic. Lesions may persist from days to weeks and then fade slowly to residual oval hyperpigmented patches.

Subsequent reexposure to the medication results in a reactivation of the site, with inflammation occurring within 30 minutes to 16 hours. [48] The reactivation of old lesions also may be associated with the development of new lesions at other sites.

Patients may not be cognizant that a drug, nutritional supplement, over-the-counter medication, or, rarely, food (eg, fruits, nuts) triggered the skin problem. They may be convinced that an insect, particularly a spider, may be the culprit. A careful history is required to elicit the fact that a drug has been taken and is temporally related to the onset of the eruption. Medications taken episodically, such as pain relievers, antibiotics, or laxatives, are often to blame. When able to be identified, patients often report ingestion of one the following types of medications [17] :

  • Analgesics

  • Muscle relaxants

  • Sedatives

  • Anticonvulsants

  • Antibiotics

Local symptoms may include pruritus, burning, and pain. [1] Systemic symptoms are uncommon, but fever, malaise, nausea, diarrhea, abdominal cramps, anorexia, and dysuria have been reported. [48, 17]

Further questioning may reveal prior episodes of fixed drug eruption, atopic disease, or other past drug reactions. Family history may render a history of atopy, drug reactions, or diabetes mellitus. [1]

Several cases of fixed drug eruption on the genitalia have been reported in patients who were not ingesting the drug but whose sexual partner was taking the offending drug and the patient was exposed to the drug through sexual contact. [49, 50, 51]


Physical Examination

The most common clinical manifestation is the pigmenting fixed drug eruption, which usually manifests as round or oval, sharply demarcated erythematous/edematous plaques located on the lip, hip, sacrum, or genitalia. [2] These erythematous patches or plaques gradually fade with residual hyperpigmentation (see images below). The center of the patch may blister or become necrotic. Other less common variants may manifest as lesions resembling erythema multiforme, toxic epidermal necrolysis, eczema, urticaria, a linear pattern following Blaschko lines, bullous lesions, a migrating eruption, or a nonpigmenting form with no postinflammatory hyperpigmentation. [3]  Pseudoephedrine, [52] piroxicam, [53] cotrimoxazole, [54] sorafenib, [55] and tadalafil [56] have all been reported to cause the nonpigmenting form of this condition.

Targetoid fixed drug eruption on the abdomen of a Targetoid fixed drug eruption on the abdomen of a child.
Hyperpigmented fixed drug eruption on the hip of a Hyperpigmented fixed drug eruption on the hip of an adult.
Vesicular fixed drug eruption on the glans penis. Vesicular fixed drug eruption on the glans penis.
Multiple hyperpigmented fixed drug eruptions on th Multiple hyperpigmented fixed drug eruptions on the trunk.
Hyperpigmented fixed drug eruption on the right si Hyperpigmented fixed drug eruption on the right side of the upper lip.

Initially, a single lesion or a few lesions develop, but, with reexposure, additional lesions occur. The vast majority of patients present with 1-30 lesions, ranging in size of 0.5-5 cm, but reports of lesions greater than 10 cm have been published. Lesions may be generalized. The most common reported site is the lips, and these may be seen in up to half of all cases. [1]

Medications may also follow a site-specific eruption pattern. For example, trimethoprim-sulfamethoxazole (Bactrim) has been shown to favor the genital region (especially in males) and naproxen and the oxicams involve the lips. [2]

Resting/inactive lesions tend to appear as round or oval, gray, hyperpigmented macules.

Upon reexposure, the resting hyperpigmented macules activate, developing a violaceous center encircled by concentric rings of erythema. Re-administration of the medication poses the risk of increased pigmentation, size, and number of lesions.

Individuals with darker pigmentation may develop postinflammatory hypopigmented macules once the lesions have resolved. [13]



Hyperpigmentation is the most likely complication of a fixed drug eruption (FDE). The potential for infection exists in the setting of multiple, eroded lesions. Generalized eruptions have been reported following topical and oral provocation testing. [17, 57]