30th July 2026

Fixed drug eruption

Background

Fixed drug eruptions (FDE) are a type of skin reaction which occurs upon exposure to a drug, with reoccurrence in the same location when re-exposed to the offending agent. Often patients develop a singular lesion, which is self-limiting but leaves an area of post-inflammatory hyperpigmentation. Initial development of the reaction may occur months to years after exposure, with later eruptions occurring more acutely.

Epidemiology

Estimates on incidence vary and range between 2-6% of patients taking medications. No gender or age preference has been found.

Aetiology

FDE is a delayed type IV hypersensitivity reaction with CD8 T cell mediation at the dermo-epidermal layer, causing keratinocyte and melanocyte damage. CD8 T-cells remain quiescent but primed in the resolved lesion until the offending agent is reintroduced.

Drugs most commonly associated with FDE include:

Antibacterial agents: trimethoprim – sulfamethoxazole, tetracyclines, penicillin, quinolones, dapsone)
NSAIDS
Paracetamol
Barbiturates
Antimalarials
Carbamazepine

FDE can uncommonly occur with food and food additives. There are also some reports of patients developing FDE secondary to COVID-19 vaccinations.

Clinical manifestations

Well-demarcated rash
Solitary or small number of lesions
Round or oval
Colour varies between red to black
Post-inflammatory hyperpigmentation
Pruritus or burning is sometimes present
Common areas affected: lips, anogenital regions, hands and feet. If mucosal surfaces are affected, ulcers may develop.
Systemic symptoms are rare

A number of clinical variants exist:

Generalised fixed drug eruption: multiple disseminated lesions affected the trunk and extremities.
Generalised bullous fixed drug eruption: usually occurs within 24 hours of the drug exposure with blistering rash affecting < 10% of the skin surface. Mucosal surfaces are not affected. Some systemic issues may occur such as fever, malaise and arthralgia but this is rare. Prognosis is good with resolution of symptoms shortly after discontinuation of the offending drug.
Non-pigmenting fixed drug eruption: symmetrical lessons that improve without post-inflammatory hyperpigmentation.

Investigations

Diagnosis is clinical, based upon the history and examination, but if there is diagnostic uncertainty, the following investigations may be considered:

Skin biopsy: necrotic keratinocytes in the epidermis, lympho-eisinophilic cells in the dermis with dermal oedema
Oral provocation test: low dose of the offending agent is administered. It is contraindicated with patients with generalised bullous fixed drug eruption.
Patch testing: application of the offending agent to area of recurring lesion to elicit a reaction.