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Fixed drug eruption

Tetsuo Shiohara, MD, PhD
Section Editor
Maja Mockenhaupt, MD, PhD
Deputy Editor
Rosamaria Corona, MD, DSc


Fixed drug eruption (FDE) is a distinctive type of cutaneous drug reaction that characteristically recurs in the same locations upon reexposure to the offending drug. Acute FDE usually presents with a single or a small number of dusky red or violaceous plaques that resolve leaving postinflammatory hyperpigmentation (picture 1A-C). Rare severe atypical variants of FDE, including multiple, nonpigmenting, and generalized bullous variants, share clinical features with Stevens-Johnson syndrome/toxic epidermal necrolysis.

FDE will be discussed in this topic. Other types of drug eruptions are discussed separately. (See "Drug eruptions" and "Exanthematous (morbilliform) drug eruption" and "Lichenoid drug eruption (drug-induced lichen planus)" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)


Cutaneous skin reactions occur in approximately 2 to 3 percent of patients taking drugs. FDEs are less common than exanthematous (morbilliform) eruptions, which are estimated to account for up to 95 percent of cutaneous drug reactions [1-3]. FDEs occur in both sexes and in all age groups; in children, FDEs account for 14 to 22 percent of cutaneous drug reactions [4,5].


Eliciting drugs — Many drugs may induce FDE. The frequency with which individual drugs cause FDE varies over time and from country to country, depending upon drug availability and rates of consumption. Drugs most frequently associated with FDE include [6-8]:

Antibacterial agents (trimethoprim-sulfamethoxazole, tetracyclines, penicillins, quinolones, dapsone)


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Literature review current through: Sep 2016. | This topic last updated: Aug 1, 2016.
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  1. Bigby M, Jick S, Jick H, Arndt K. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA 1986; 256:3358.
  2. Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol 2001; 137:765.
  3. Lee AY. Fixed drug eruptions. Incidence, recognition, and avoidance. Am J Clin Dermatol 2000; 1:277.
  4. Khaled A, Kharfi M, Ben Hamida M, et al. Cutaneous adverse drug reactions in children. A series of 90 cases. Tunis Med 2012; 90:45.
  5. Sharma VK, Dhar S. Clinical pattern of cutaneous drug eruption among children and adolescents in north India. Pediatr Dermatol 1995; 12:178.
  6. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol 1998; 37:833.
  7. Brahimi N, Routier E, Raison-Peyron N, et al. A three-year-analysis of fixed drug eruptions in hospital settings in France. Eur J Dermatol 2010; 20:461.
  8. Nnoruka EN, Ikeh VO, Mbah AU. Fixed drug eruption in Nigeria. Int J Dermatol 2006; 45:1062.
  9. Jhaj R, Asati DP, Chaudhary D. Fixed drug eruption due to levocetirizine. J Pharmacol Pharmacother 2016; 7:109.
  10. Kim MY, Jo EJ, Chang YS, et al. A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives. Asia Pac Allergy 2013; 3:281.
  11. Shiohara T, Mizukawa Y. Fixed drug eruption: a disease mediated by self-inflicted responses of intraepidermal T cells. Eur J Dermatol 2007; 17:201.
  12. Shiohara T, Moriya N. Epidermal T cells: their functional role and disease relevance for dermatologists. J Invest Dermatol 1997; 109:271.
  13. Shiohara T, Mizukawa Y, Teraki Y. Pathophysiology of fixed drug eruption: the role of skin-resident T cells. Curr Opin Allergy Clin Immunol 2002; 2:317.
  14. Komatsu T, Moriya N, Shiohara T. T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR V alpha-V beta genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption. Clin Exp Immunol 1996; 104:343.
  15. Mizukawa Y, Yamazaki Y, Teraki Y, et al. Direct evidence for interferon-gamma production by effector-memory-type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption. Am J Pathol 2002; 161:1337.
  16. Mizukawa Y, Yamazaki Y, Shiohara T. In vivo dynamics of intraepidermal CD8+ T cells and CD4+ T cells during the evolution of fixed drug eruption. Br J Dermatol 2008; 158:1230.
  17. Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009; 9:316.
  18. Shiohara T, Mizukawa Y. The immunological basis of lichenoid tissue reaction. Autoimmun Rev 2005; 4:236.
  19. Shelley WB, Shelley ED. Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline. J Am Acad Dermatol 1987; 17:403.
  20. Agnew KL, Oliver GF. Neutrophilic fixed drug eruption. Australas J Dermatol 2001; 42:200.
  21. Ozkaya E, Büyükbabani N. Neutrophilic fixed drug eruption caused by naproxen: a real entity or a stage in the histopathologic evolution of the disease? J Am Acad Dermatol 2005; 53:178.
  22. Harris A, Burge SM. Vasculitis in a fixed drug eruption due to paracetamol. Br J Dermatol 1995; 133:790.
  23. Mockenhaupt M. Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges 2009; 7:142.
  24. Korkij W, Soltani K. Fixed drug eruption. A brief review. Arch Dermatol 1984; 120:520.
  25. Mizukawa Y, Shiohara T. Trauma-localized fixed drug eruption: involvement of burn scars, insect bites and venipuncture sites. Dermatology 2002; 205:159.
  26. Shiohara T, Mizukawa Y. Recall phenomenon: some skin-resident cells remember previous insults. Dermatology 2003; 207:127.
  27. Breathnach SM. Drug reactions. In: Rook's Textbook of Dermatology, 8th ed, Burns T, Breathnach SM, Cox NH, Griffiths C (Eds), Wiley-Blackwell, Hoboken, NJ 2010. Vol IV.
  28. Ozkaya E. Polysensitivity in fixed drug eruption due to a novel drug combination-independent lesions due to piroxicam and cotrimoxazole. Eur J Dermatol 2006; 16:591.
  29. Walfish AE, Sapadin AN. Fixed drug eruption due to doxycycline and metronidazole. Cutis 2002; 69:207.
  30. Mizukawa Y, Shiohara T. Fixed drug eruption presenting as erythema dyschromicum perstans: a flare without taking any medications. Dermatology 1998; 197:383.
  31. Baird BJ, De Villez RL. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol 1988; 27:170.
  32. Bandino JP, Wohltmann WE, Bray DW, Hoover AZ. Naproxen-induced generalized bullous fixed drug eruption. Dermatol Online J 2009; 15:4.
  33. Ada S, Yilmaz S. Ciprofloxacin-induced generalized bullous fixed drug eruption. Indian J Dermatol Venereol Leprol 2008; 74:511.
  34. Cho YT, Lin JW, Chen YC, et al. Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features. J Am Acad Dermatol 2014; 70:539.
  35. Lipowicz S, Sekula P, Ingen-Housz-Oro S, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 2013; 168:726.
  36. Mizukawa Y, Shiohara T. Nonpigmenting fixed drug eruption as a possible abortive variant of toxic epidermal necrolysis: immunohistochemical and serum cytokine analyses. Clin Exp Dermatol 2010; 35:493.
  37. Baran R, Perrin C. Fixed-drug eruption presenting as an acute paronychia. Br J Dermatol 1991; 125:592.
  38. Sigal-Nahum M, Konqui A, Gaulier A, Sigal S. Linear fixed drug eruption. Br J Dermatol 1988; 118:849.
  39. Guin JD, Baker GF. Chronic fixed drug eruption caused by acetaminophen. Cutis 1988; 41:106.
  40. Miah MA, Ahmed SS, Chowdhury SA, et al. Fixed drug eruptions due to cotrimoxazole. Mymensingh Med J 2008; 17:S1.
  41. Mahboob A, Haroon TS, Iqbal Z, et al. Fixed drug eruption: topical provocation and subsequent phenomena. J Coll Physicians Surg Pak 2006; 16:747.
  42. Ozkaya-Bayazit E, Bayazit H, Ozarmagan G. Topical provocation in 27 cases of cotrimoxazole-induced fixed drug eruption. Contact Dermatitis 1999; 41:185.