Fixed Drug Eruption: Definition, Triggers, and Management
What is Fixed Drug Eruption?
Fixed drug eruption (FDE) is a distinctive cutaneous drug reaction characterized by recurrent lesions appearing at the exact same anatomical site each time the causative medication is ingested. 1, 2 The lesions typically present as round or oval, sharply demarcated erythematous or edematous plaques that resolve with characteristic hyperpigmentation after drug discontinuation. 1, 3
Key Diagnostic Features
The diagnosis is primarily clinical and requires three essential historical elements: 1
- Recurrence at identical anatomical sites with each drug exposure
- Clear temporal relationship between drug intake and symptom onset (typically 1-24 hours for recurrent episodes) 2
- Resolution with residual hyperpigmentation after drug withdrawal 1
Common Drug Triggers
Most Frequent Causative Agents
NSAIDs are among the most common causes of FDE, particularly oxicam derivatives (meloxicam, piroxicam), acetic acid derivatives (diclofenac), and propionic acid derivatives. 4, 3 Other major categories include:
- Antibiotics: Co-trimoxazole (most common overall), other sulfonamides 2
- Antiepileptics: Carbamazepine and other aromatic anticonvulsants 5
- Acetaminophen (paracetamol) 4
- Pseudoephedrine: Can cause both pigmenting and non-pigmenting variants 6
- Nitroimidazole derivatives: High cross-reactivity within this class 7
Critical Cross-Reactivity Patterns
Cross-reactivity within the same chemical class is well-described but not universal. 4 For NSAIDs, lack of cross-reactivity between ibuprofen and naproxen has been reported for FDE, though cross-reactivity within the same structural class remains possible. 4 Patients with nitroimidazole-induced FDE should avoid all drugs in this class due to high cross-reactivity risk. 7
Management Algorithm
Step 1: Immediate Action
Immediately and permanently discontinue the causative drug—this is the cornerstone of FDE management and directly impacts prognosis. 1, 2 Failure to remove the offending agent can lead to:
- Increased inflammation and hyperpigmentation with each recurrence 2
- Progression to potentially lethal generalized bullous FDE (GBFDE) 2, 8
- Risk of life-threatening complications resembling SJS/TEN 2
Step 2: Obtain Comprehensive Medication History
Document all medications from the previous 2 months, including: 1, 5
- Prescription medications with exact start/stop dates
- Over-the-counter drugs
- Complementary and alternative therapies
- Exact date when first symptoms appeared 1
Step 3: Topical Treatment for Localized FDE
For localized or mild FDE, apply moderate-to-high potency topical corticosteroids such as: 1
- Mometasone furoate 0.1% ointment twice daily, OR
- Betamethasone valerate 0.1% ointment twice daily
Supportive care measures include: 1
- Applying emollients regularly
- Avoiding hot showers and excessive soap use
- Limiting sun exposure to affected areas
Step 4: Hospitalization Criteria
Hospitalize patients with: 1
- Extensive body surface area involvement
- Systemic symptoms (fever, malaise)
- Suspicion of progression to SJS/TEN
- Generalized bullous FDE with widespread skin denudation 8
Step 5: Documentation and Prevention
Document the reaction thoroughly in the medical record as a drug allergy, including: 1, 7
- Specific drug implicated
- Description of the reaction
- Anatomical sites of involvement
- Clear labeling as "drug allergy" to prevent future re-exposure 7
Critical Pitfalls to Avoid
Do NOT Perform Oral Challenge Testing
Oral challenge testing is NOT recommended despite its ability to confirm the causative agent, due to risk of severe exacerbation or possible generalization to life-threatening GBFDE. 2 Patch testing on healed lesional skin is the preferred confirmatory method when diagnostic uncertainty exists, though it has poor sensitivity. 7
Do NOT Attempt Desensitization
Desensitization protocols lack supporting evidence for FDE and should not be used in routine clinical practice. 7 This approach requires specialist supervision and is not appropriate for this reaction type.
Distinguish GBFDE from SJS/TEN
Generalized bullous FDE can be distinguished from SJS/TEN by: 2
- More rapid onset (1-24 hours vs. weeks)
- Less or no mucosal involvement
- Less systemic involvement
- Tendency for more favorable prognosis (though recent experience suggests it may still be life-threatening) 2
Warning About Rechallenge
Rechallenge with the offending drug can lead to serious and possibly fatal reactions. 5 Patients must be educated that the reaction will recur at the same sites if re-exposed to the drug. 1
Follow-Up and Patient Education
Schedule follow-up at 4 weeks to: 1
- Confirm complete resolution
- Reinforce permanent avoidance of causative medication
- Educate about cross-reactive drugs to avoid 4
Educate patients to: 7
- Avoid all structurally similar drugs (particularly for nitroimidazoles and NSAIDs within the same class)
- Inform all healthcare providers about this drug allergy
- Understand that recurrence is certain with re-exposure
When to Refer to Dermatology
Consider dermatology consultation for: 7
- Diagnostic uncertainty or atypical presentation
- Generalized bullous FDE with extensive skin involvement
- Need for confirmatory patch testing
- Recurrent episodes despite reported drug avoidance