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Drug reactionCommonICD-10 L27.1

Fixed drug eruption

FDE ยท generalised bullous FDE (GBFDE) when extensive

Fixed drug eruption is a delayed-type hypersensitivity reaction characterised by single or few round, sharply demarcated, dusky red-violet patches that recur at the same site with every re-exposure to the culprit drug. Common offenders are paracetamol, sulfonamides, NSAIDs, tetracyclines, antibiotics and laxatives (phenolphthalein historically). Residual hyperpigmented patches commonly persist for months and are a frequent skin-oncology DDx for naevus or melanocytic neoplasia. The generalised bullous variant (GBFDE) can overlap clinically with SJS/TEN.

CurrentLast reviewed 16 May 2026
Clinical image of Fixed drug eruption
Fixed drug eruption. Image sourced from DermNet New Zealand. Used under CC BY-NC-ND 4.0. No endorsement implied.

Aetiology

  • Common culprits:
    • Paracetamol, NSAIDs (ibuprofen, mefenamic acid, naproxen).
    • Sulfonamides (sulfamethoxazole, sulfasalazine).
    • Antibiotics โ€” tetracyclines, fluoroquinolones, ฮฒ-lactams.
    • Anticonvulsants โ€” carbamazepine, phenytoin.
    • Laxatives โ€” phenolphthalein (historical).
    • Allopurinol, antimalarials, OCP.
  • Mechanism: CD8+ memory T cells resident in the epidermis at the previously affected site re-activate on drug exposure.
  • Onset minutes to days after re-exposure; faster with each recurrence.

Clinical features

  • One or few round / oval sharply demarcated dusky red-violet patches; 1-10 cm; well-circumscribed.
  • Sites: lips, genitalia (penis, glans), face, hands, mucosae; recur at the same site with each re-exposure.
  • Burning / itching with new lesions; bulla may form in centre.
  • Resolution over 2-4 weeks with characteristic residual hyperpigmentation that may persist for months / years.
  • Generalised bullous fixed drug eruption (GBFDE): multiple large dusky patches with bullae; can affect >10% BSA; potentially severe and confused with SJS/TEN โ€” mucosal involvement is typically minimal.
  • Variants: non-pigmenting, bullous, urticarial, eczematous, mucosal-only (oral / genital), psoriasiform.

Investigations

  • Clinical diagnosis based on history + same-site recurrence.
  • Drug provocation testing: oral / topical / patch testing at the affected site can confirm culprit (specialist setting).
  • Skin biopsy of active lesion: interface dermatitis, vacuolar degeneration, dyskeratotic keratinocytes, dermal melanophages (pigment-incontinence โ€” accounts for residual hyperpigmentation).
  • Detailed drug history (including OTC, herbal, intermittent โ€” paracetamol commonly missed).

Differentials

  • Naevus / melanocytic lesion โ€” single round pigmented patch on glans / lip; biopsy if uncertain.
  • Erythema multiforme โ€” true target lesions; HSV-driven.
  • Phytophotodermatitis โ€” streaky pattern; phototoxic.
  • Genital herpes โ€” vesicles; PCR.
  • Fixed pigment lesion โ€” lichen planus, sarcoidosis.
  • SJS / TEN / GBFDE โ€” generalised; mucosal involvement.
  • Tinea, candidiasis in genital cases.

Management

  • Withdraw and avoid culprit drug โ€” pharmacy alert, MedicAlert.
  • Symptomatic:
    • Mid-to-potent topical corticosteroids during active phase.
    • Oral antihistamines for pruritus.
    • Cool compresses for bullous lesions.
  • GBFDE:
    • Admit if extensive bullae, systemic features, or diagnostic uncertainty (SJS/TEN exclusion).
    • Supportive care; systemic corticosteroids in selected severe cases.
  • Residual hyperpigmentation:
    • Sun protection; hydroquinone 4%; tretinoin; Q-switched / picosecond laser if persistent.
    • Counsel: pigment may take months-years to fade; persistence common, particularly in Fitzpatrick IV-VI.
  • Document drug allergy and counsel re class cross-reactivity (e.g. sulfonamide antibiotics vs sulfonylureas โ€” generally no cross-reactivity).

References

  1. Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol. 2009;9:316-321.
  2. Brahimi N et al. Fixed drug eruption: a review of the literature. Indian J Dermatol Venereol Leprol. 2020;86:631-639.
  3. Lee AY. Fixed drug eruptions: incidence, recognition, and avoidance. Am J Clin Dermatol. 2000;1:277-285.
  4. Cho YT, Lin JW, Chen YC. Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome / toxic epidermal necrolysis by immunohistopathological features. J Am Acad Dermatol. 2014;70:539-548.

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