From the Guidelines
Fixed drug eruption (FDE) is a type of drug reaction that requires immediate discontinuation of the offending medication to prevent further morbidity and mortality, and management primarily involves symptomatic treatment with topical corticosteroids and oral antihistamines. The lesions typically present as round or oval, sharply demarcated patches that are erythematous to violaceous in color, sometimes developing into blisters in severe cases [ 1 ]. Common locations include the lips, genitalia, hands, and feet, though they can appear anywhere on the body. The most frequent causative medications include antibiotics (particularly sulfonamides, tetracyclines, and fluoroquinolones), NSAIDs (especially naproxen), anticonvulsants, and some antimalarials.
Key Considerations
- The pathophysiology involves a delayed type IV hypersensitivity reaction with memory CD8+ T cells residing in the affected skin, explaining why lesions recur in the same locations [ 1 ].
- Prevention focuses on avoiding the identified trigger medication and potentially cross-reactive drugs, with patients being advised to carry documentation of their drug allergy.
- In severe or widespread cases, short courses of systemic corticosteroids may be necessary.
Management Approach
- Identifying and discontinuing the offending drug is crucial, which usually leads to resolution within 7-14 days [ 1 ].
- Symptomatic treatment includes:
- Topical corticosteroids for localized lesions
- Oral antihistamines for pruritus
- Short courses of systemic corticosteroids in severe cases
Important Considerations
- Post-inflammatory hyperpigmentation often persists after resolution of the lesions.
- Patients should be advised to avoid the identified trigger medication and potentially cross-reactive drugs to prevent further reactions [ 1 ].
From the Research
Definition and Characteristics of Fixed Drug Eruption
- A fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested 2, 3.
- FDE is defined as a same-site recurrence with exposure to a particular medication 2.
- Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE) 3.
Diagnosis and Management
- The primary approach and treatment for all types of FDEs are to identify and remove the causative agent, often accomplished by a thorough history of medication and other chemical exposures, and possibly prior episodes 2.
- Patch testing is now preferred over oral challenge testing to confirm the causative agent due to the risk of severe exacerbation or possible generalization 2.
- Treatment of localized FDE includes medication removal, patient counseling, and symptomatic relief 2.
- Failure to remove the causative agent in localized FDE can lead to recurrence, which is associated with increased inflammation, hyperpigmentation, and risk of a potentially lethal GBFDE 2.
Generalized Bullous Fixed Drug Eruption (GBFDE)
- GBFDE is a rare and severe variant of FDE, presenting with widespread bullae accompanied by characteristic FDE lesions 3, 4.
- GBFDE may resemble Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), but can be distinguished by its more rapid onset, less or no mucosal involvement, and a tendency for a more favorable prognosis 2.
- However, recent experience suggests that GBFDE may be just as life-threatening as SJS or TEN 2.
Common Culprits and Cross-Reactivity
- The most frequently implicated drugs in FDE include analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs] and paracetamol) and antibiotics 5.
- Newer, novel agents of note include cyclooxygenase-2 specific inhibitors, fluconazole, and phosphodiesterase 5 inhibitors 5.
- Cross-reactivity between different groups of NSAIDs has been rarely reported in FDE cases, but can occur, as seen in a case of paracetamol-induced GBFDE followed by FDE triggered by cross-reactivity with dipyrone (metamizole) 4.