Fixed Drug Eruptions

  • Kara M. Pretzlaff
  • Amit G. Pandya
  • Arturo R. Dominguez


Fixed Drug Eruptions (FDEs) are a localized response to medications that typically appear as well-demarcated erythematous dusky patches or plaques. They may be solitary, multiple, or generalized. The initial eruption of a FDE appears 1 week post-drug exposure, whereas subsequent exposures to the same drug lead to development of lesions within 30 min to 24 h. Despite the number of occurrences, these patches and plaques resolve within 2–3 weeks of discontinuing the offending agent, often leaving post-inflammatory hyperpigmentation. NSAIDs (non-steroidal anti-inflammatory drugs), tetracyclines, trimethoprim-sulfamethoxazole, sedatives including barbiturates, benzodiazepines and chlordiazepoxide, and anti-convulsants are the most commonly reported drugs causing FDE. Certain drugs have a predilection for causing particular subtypes of FDE, as well as mucosal involvement. Histologically, FDEs present with a vacuolar dermatitis occurring at the dermo-epidermal junction. Lymphocyte infiltration and hydropic degeneration of keratinocytes develop over the first 24 h following exposure, which can progress to separation of the dermis and epidermis with subepidermal bullae formation. The immunologic mechanism of FDE involves activation of CD8+ T cells that release interferon gamma, granzymes, and perforins, leading to recruitment of neutrophils, CD4+ T cells, mast cells, and occasionally eosinophils. Diagnosis of FDE is largely clinical and treatment is comprised of discontinuing the offending drug and treating symptoms, such as pruritus and pain. However, if the offending agent is unclear, patch testing or oral re-challenge at sub-therapeutic doses are the preferred diagnostic tests.


Toxic epidermal necrolysis (TEN) Erythema multiforme (EM) Targetoid lesions NSAIDs Tetracylines Polysensitivity Pigmentary incontinence Vacuolar dermatitis CD8 T-cells Patch testing 

Suggested Reading

  1. Andrade P, Brinca A, Gonçalo M. Patch testing in fixed drug eruptions—a 20-year review. Contact Dermatitis. 2011;65(4):195–201.CrossRefPubMedGoogle Scholar
  2. Browne SG. Fixed eruption in deeply pigmented subjects: clinical observations on 350 patients. Br Med J. 1964;2(5416):1041–4.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Fischer G. Vulvar fixed drug eruption. A report of 13 cases. J Reprod Med. 2007;52(2):81–6.PubMedGoogle Scholar
  4. Hindsen M, Christensen OB, Gruic V, et al. Fixed drug eruption: an immunohistochemical investigation of the acute and healing phase. Br J Dermatol. 1987;116(3):351–60.CrossRefPubMedGoogle Scholar
  5. Korkij W, Soltani K. Fixed drug eruption. A brief review. Arch Dermatol. 1984;120(124):520.CrossRefPubMedGoogle Scholar
  6. Krivda SJ, Benson PM. Nonpigmenting fixed drug eruption. J Am Acad Dermatol. 1994;31(2 Pt 1):291–2.CrossRefPubMedGoogle Scholar
  7. Lee AY. Fixed drug eruptions: Incidence, recognition, and avoidance. Am J Clin Dermatol. 2000;1(5):277–85.CrossRefPubMedGoogle Scholar
  8. Lipowicz S, Sekula P, Ingen-Housz-Oro S, Liss Y, Sassolas B, Dunant A, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2013;168:726–32.CrossRefPubMedGoogle Scholar
  9. Litt JZ. Litt’s drug eruptions and reactions manual. 19th ed. Philadelphia: CRC Publishing; 2001.Google Scholar
  10. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol. 1998;37(11):833–8.CrossRefPubMedGoogle Scholar
  11. Masu S, Seiji M. Pigmentary incontinence in fixed drug eruptions. Histologic and electron microscopic findings. J Am Acad Dermatol. 1983;8(4):525–32.CrossRefPubMedGoogle Scholar
  12. Morelli JG, Tay Y-K, Rogers M, et al. Fixed drug eruptions in children. J Pediatr. 1999;134(3):365–7.CrossRefPubMedGoogle Scholar
  13. Ozkaya E. Oral mucosal fixed drug eruption: Characteristics and differential diagnosis. J Am Acad Dermatol. 2013;69(2):e51–8.CrossRefPubMedGoogle Scholar
  14. Ozkaya E, Babuna G. A challenging case: Symmetrical drug related intertriginous and flexural exanthema, fixed drug eruption, or both? Pediatr Dermatol. 2011;28(6):711–4.CrossRefPubMedGoogle Scholar
  15. Paller AS, Mancini AJ. Hurwitz clinical pediatric dermatology: a textbook of skin disorders of childhood and adolescence. 4th ed. Philadelphia: Elsevier Inc; 2011.Google Scholar
  16. Pandhi RK, Kumar AS, Satish DA, Bhutani LK. Fixed drug eruptions on male genitalia: a clinical and etiological study. Sex Transm Dis. 1984;11:164–6.CrossRefPubMedGoogle Scholar
  17. Pranay T, Sandeep KA, Chhabra S. Civatte bodies: a diagnostic clue. Indian J Dermatol. 2013;58(4):327.PubMedPubMedCentralGoogle Scholar
  18. Shelley WB, Shelley ED. Nonpigmenting fixed drug eruption as a distinctive reaction pattern: Examples caused by sensitivities to pseudoephedrine hydrochloride and tetrahydrozoline. J Am Acad Dermatol. 1987;17(3):403–7.CrossRefPubMedGoogle Scholar
  19. Shiohara T. Fixed drug eruption. 2014.
  20. Teraki Y, Shiohara T. IFN-gamma-producing effector CD8+ T cells and IL-10-producing regulatory CD4+ T cells in fixed drug eruption. J Allergy Clin Immunol. 2003;112(3):609–15.CrossRefPubMedGoogle Scholar
  21. Umpierrez A, Cuesta-Herranz J, De Las Heras M, Lluch-Bernal M, Figueredo E, Sastre J. Successful desensitization of a fixed drug eruption caused by allopurinol. J Allergy Clin Immunol. 1998;101(2 pt 1):286–7.CrossRefPubMedGoogle Scholar
  22. Wolfgang W, Dieter M. Histopathology of drug eruptions – general criteria, common patterns, and differential diagnosis. Dermatol Pract Concept. 2011;1(1):33–47.Google Scholar

Copyright information

© Springer-Verlag London 2015

Authors and Affiliations

  • Kara M. Pretzlaff
    • 1
  • Amit G. Pandya
    • 2
  • Arturo R. Dominguez
    • 2
  1. 1.Department of DermatologyUT Southwestern Medical SchoolDallasUSA
  2. 2.Department of DermatologyUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations