Updated Protocol for Diagnosis and Management of Fixed Drug Eruption
Diagnosis
The diagnosis of fixed drug eruption (FDE) is primarily clinical, based on three essential historical features: recurrence at the same anatomical site, temporal relationship to drug exposure, and resolution with hyperpigmentation after drug discontinuation. 1
Essential History Components
Obtain a complete medication timeline covering the previous 2 months, including all prescription drugs, over-the-counter medications, and complementary/alternative therapies, with exact dates when medications were started, stopped, or dose-escalated. 1
Document the index date (when the first symptom or sign appeared) and track the progression of the eruption daily. 2
Inquire specifically about recurrence patterns: Ask whether similar lesions have appeared at the same anatomical sites with previous drug exposures, as this is pathognomonic for FDE. 1
Identify common anatomical sites: FDE most commonly occurs on the genitals, lips, trunk, and hands, though it can occur at any location. 3
Clinical Examination
Look for well-defined, circular, hyperpigmenting plaques that present as one or a few lesions in fixed locations. 3
Examine all mucosal sites for involvement, noting symptoms like dysuria or retention if genital mucosa is affected. 2
Record baseline vital signs and measure oxygen saturation with pulse oximeter to assess for systemic involvement. 2
Diagnostic Confirmation
Perform a small punch biopsy if the diagnosis is uncertain, as histopathologic examination can confirm FDE. 3
Immunohistochemical findings may show intraepidermal T cells distributed between basal and suprabasal keratinocytes in lesional skin, which is suggestive of FDE. 4
Consider that FDE can present atypically as multiple pigmented macules that flare at fixed sites even without recent medication exposure, mimicking erythema dyschromicum perstans. 4
Management
Immediate and permanent discontinuation of the causative drug is the cornerstone of FDE management and directly impacts prognosis. 1
Acute Treatment Protocol
For localized/mild FDE:
Apply topical moderate-to-high potency corticosteroids such as mometasone furoate 0.1% or betamethasone valerate 0.1% ointment twice daily to affected areas. 1, 5
Use oral antihistamines for symptomatic relief of pruritus: second-generation agents like loratadine 10 mg daily for daytime, or first-generation agents like diphenhydramine 25-50 mg or hydroxyzine 25-50 mg for nighttime sedation. 5
For extensive involvement:
Hospitalization is indicated for extensive body surface area involvement, systemic symptoms, or suspicion of progression to Stevens-Johnson syndrome/toxic epidermal necrolysis. 1
Provide supportive care including applying emollients, avoiding hot showers and excessive soap use, and limiting sun exposure. 1
Drug Avoidance and Cross-Reactivity
Educate patients that cross-reactivity with structurally similar drugs is possible and that these drugs should also be avoided. 1
Counsel patients that the reaction will recur at the same sites if re-exposed to the drug, typically within hours of administration. 1, 6
Documentation and Follow-Up
Document the reaction thoroughly in the medical record to prevent future re-exposure, including the specific drug implicated, description of the reaction, and sites of involvement. 1
Provide written information about drug(s) to avoid and encourage wearing a MedicAlert bracelet. 2
Document drug allergy in the patient's notes and inform all healthcare providers involved in the patient's care. 2
Report the episode to pharmacovigilance authorities as recommended for all drug eruptions. 2
Schedule follow-up at 4 weeks to confirm resolution and reinforce avoidance of the causative medication. 1
Common Pitfalls
Do not dismiss FDE because it lacks characteristics of common morbilliform drug rashes—the diagnosis is often missed for this reason. 3
Be aware that FDE can flare without recent drug exposure in some cases, though this is uncommon and should not delay diagnosis if the history is otherwise consistent. 4
Resolution typically occurs within days to weeks after the offending drug is discontinued, leaving residual hyperpigmentation that gradually fades. 3, 6