What is a fixed drug eruption, which medications commonly cause it, and what is the recommended management?

Fixed Drug Eruption: Definition, Causative Medications, and Management

What is a Fixed Drug Eruption?

Fixed drug eruption (FDE) is a distinctive drug-induced cutaneous reaction characterized by recurrence at the same anatomical site upon re-exposure to the causative medication, presenting as sharply demarcated, round to oval, erythematous or violaceous plaques that resolve with residual hyperpigmentation. 1, 2

The diagnosis is primarily clinical and based on three essential historical features: 1

• Recurrence at the same anatomical site with each drug exposure
• Temporal relationship to drug exposure (onset can occur within 1-24 hours of re-exposure, or days to weeks with initial exposure)
• Resolution with hyperpigmentation after drug discontinuation

FDE lesions can range from pink to dark red to brown, may exceed 10 cm in size, and in approximately one-third of cases progress to vesicles or bullae. 3, 4

Common Causative Medications

NSAIDs are among the most common causes of FDE, particularly oxicam derivatives (meloxicam, piroxicam), acetic acid derivatives (diclofenac), propionic acid derivatives (ibuprofen, naproxen), and acetaminophen. 5

Other major categories include: 5, 4, 6

• Antibiotics: Co-trimoxazole (most common overall), sulfonamides, tetracyclines
• Antiepileptics: Carbamazepine, phenytoin, other aromatic anticonvulsants
• Analgesics: NSAIDs account for up to 40% of FDE cases in some series

Cross-reactivity within the same chemical class is well-described but not universal (e.g., lack of cross-reactivity between ibuprofen and naproxen has been reported for FDE). 5

Recommended Management

Immediate Actions

Immediately and permanently discontinue the causative drug—this is the cornerstone of FDE management and directly impacts prognosis. 1

When FDE is suspected: 1

• Obtain a complete medication history covering the previous 2 months, including prescription drugs, over-the-counter medications, and complementary/alternative therapies
• Document exact dates when medications were started, stopped, or dose-escalated, as well as the index date when first symptoms appeared
• Stop all suspected medications immediately upon recognition

Treatment Based on Severity

For localized/mild FDE: 1

• Apply topical moderate-to-high potency corticosteroids (mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) twice daily to affected areas
• Apply emollients regularly to reduce dryness and prevent recurrence
• Avoid hot showers, excessive soap use, and limit sun exposure

For extensive involvement or systemic symptoms: 1

• Hospitalization is indicated for extensive body surface area involvement, systemic symptoms, or suspicion of progression to Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
• Provide supportive care with emollients and symptom management

Critical Diagnostic Distinction

Generalized bullous FDE (GBFDE) can masquerade as SJS/TEN but has distinguishing features: 7, 4

• More rapid onset (1-24 hours rather than weeks)
• Less or no mucosal involvement
• Less or no systemic involvement
• Tendency for more favorable prognosis, though recent experience suggests it may still be life-threatening

This distinction is critical because classic SJS/TEN warrants aggressive resuscitation and burn unit admission, while obvious bullous FDE can be managed more conservatively. 7

Documentation and Prevention

Document the reaction thoroughly in the medical record to prevent future re-exposure: 1

• Specific drug implicated
• Description of the reaction
• Sites of involvement

Educate patients that: 1, 8

• The reaction will recur at the same sites if re-exposed to the drug
• Cross-reactivity with structurally similar drugs is possible and these should be avoided
• Rechallenge with the offending drug can lead to serious and possibly fatal reactions 8

Follow-Up

Follow-up at 4 weeks is recommended to confirm resolution and reinforce avoidance of the causative medication. 1

Important Caveats

Avoid oral challenge testing to confirm the causative agent due to risk of severe exacerbation or possible generalization; patch testing is now preferred if confirmation is needed. 4

Failure to remove the causative agent in localized FDE can lead to recurrence, which is associated with increased inflammation, hyperpigmentation, and risk of potentially lethal generalized bullous FDE. 4

For NSAIDs within the same class, avoidance without rechallenge is recommended for severe reactions due to potential cross-reactivity. 5