eMedicine Specialties > Dermatology > Allergy & Immunology

Fixed Drug Eruptions: Differential Diagnoses & Workup

Author: David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
Coauthor(s): Jordan R Ilse, MD, Staff Physician, Scott and White Internal Medicine Residency Program, Temple, Texas
Contributor Information and Disclosures

Updated: Aug 24, 2009

Differential Diagnoses

Bullous Pemphigoid
Lichen Planus Actinicus
Cellulitis
Lupus Erythematosus, Discoid
Drug Eruptions
Melasma
Drug-Induced Bullous Disorders
Pemphigus Vulgaris
Eczema
Pemphigus, Drug-Induced
Erythema Annulare Centrifugum
Pityriasis Rosea
Erythema Dyschromicum Perstans
Postinflammatory Hyperpigmentation
Erythema Multiforme
Psoriasis
Herpes Simplex
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Insect Bites
Urticaria, Acute
Lichen Planus

Workup

Laboratory Studies

Blood studies are not useful for the diagnosis of fixed drug eruption (FDE), although eosinophilia is common with drug eruptions.

Other Tests

Rechallenging the patient to the suspected offending drug is the only known test to possibly discern the causative agent. Patch testing of the suspected drug to lesional and non-lesional skin has been helpful in a few instances. The exact protocol of patch testing has varied.

Patch testing and oral provocation have been used to identify the suspected agent and check for cross-sensitivities to medications.32,33 A refractory period has been reported in fixed drug eruption; therefore, a delay before and between patch testing and oral provocation is recommended. One study used an 8-week time window after lesion resolution and between tests, which yielded positive results.34 Patch testing must be performed on a previously involved site; otherwise, a false-negative result is likely.33 Some locations may be inappropriate for patch testing; thus, clinical discretion is advised. Once patch testing is complete, oral provocation should follow, with the least likely culprits and the negative patch test agents first, followed by more likely causes. Oral provocation is thought to be the only reliable way to diagnose fixed drug eruption.

Procedures

Skin biopsy is the diagnostic procedure of choice.

Histologic Findings

Histological examination of inflammatory/acute lesions shows an interface dermatitis with vacuolar change and Civatte bodies8 (see Media File 6). The overall pattern may mimic that seen in erythema multiforme. Dyskeratosis and individual necrotic keratinocytes within the epidermis may be a prominent feature (see Media File 7). On occasion, the lymphocytic infiltrate can be prominent enough to obscure the dermoepidermal junction. Spongiosis, dermal edema, eosinophils, and occasional neutrophils may be present. Pigmentary incontinence within the papillary dermis is a characteristic feature and may be the only feature seen in older, noninflamed lesions. Chronic or inactive lesions may also show mild acanthosis, hyperkeratosis, and relatively few inflammatory cells.

Acute interface dermatitis with prominent vacuola...

Acute interface dermatitis with prominent vacuolar change and individual necrotic keratinocytes within the epidermis (X10).

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Acute interface dermatitis with prominent vacuola...

Acute interface dermatitis with prominent vacuolar change and individual necrotic keratinocytes within the epidermis (X10).



Interface dermatitis, vacuolar change, necrotic k...

Interface dermatitis, vacuolar change, necrotic keratinocytes, and incontinent pigment in the dermis (X40).

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Interface dermatitis, vacuolar change, necrotic k...

Interface dermatitis, vacuolar change, necrotic keratinocytes, and incontinent pigment in the dermis (X40).


More on Fixed Drug Eruptions

Overview: Fixed Drug Eruptions
Differential Diagnoses & Workup: Fixed Drug Eruptions
Treatment & Medication: Fixed Drug Eruptions
Follow-up: Fixed Drug Eruptions
Multimedia: Fixed Drug Eruptions
References
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References

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  4. Fischer G. Vulvar fixed drug eruption. A report of 13 cases. J Reprod Med. Feb 2007;52(2):81-6. [Medline].

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  14. Baird BJ, De Villez RL. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol. Apr 1988;27(3):170-4. [Medline].

  15. Pellicano R, Ciavarella G, Lomuto M, Di Giorgio G. Genetic susceptibility to fixed drug eruption: evidence for a link with HLA-B22. J Am Acad Dermatol. Jan 1994;30(1):52-4. [Medline].

  16. Pellicano R, Lomuto M, Ciavarella G, Di Giorgio G, Gasparini P. Fixed drug eruptions with feprazone are linked to HLA-B22. J Am Acad Dermatol. May 1997;36(5 Pt 1):782-4. [Medline].

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  19. Sehgal VN, Srivastava G. Fixed drug eruption (FDE): changing scenario of incriminating drugs. Int J Dermatol. Aug 2006;45(8):897-908. [Medline].

  20. Zawar V, Chuh A. Fixed drug reaction may be sexually induced. Int J Dermatol. Aug 2006;45(8):1003-4; author reply 1004. [Medline].

  21. Berger RE. Fixed drug eruption--a sexually inducible reaction?. J Urol. Jun 2005;173(6):1990. [Medline].

  22. Zawar V, Kirloskar M, Chuh A. Fixed drug eruption - a sexually inducible reaction?. Int J STD AIDS. Aug 2004;15(8):560-3. [Medline].

  23. Lopez Abad R, Iriarte Sotes P, Castro Murga M, Gracia Bara MT, Sesma Sanchez P. Fixed drug eruption induced by phenylephrine: a case of polysensitivity. J Investig Allergol Clin Immunol. 2009;19(4):322-3. [Medline].

  24. Gupta S, Gupta S, Mittal A, David S. Oral fixed drug eruption caused by gabapentin. J Eur Acad Dermatol Venereol. Feb 19 2009;[Medline].

  25. Ghosh SK, Bandyopadhyay D. Clopidogrel-induced fixed drug eruption. J Eur Acad Dermatol Venereol. Jan 20 2009;[Medline].

  26. Oyama N, Kaneko F. Solitary fixed drug eruption caused by finasteride. J Am Acad Dermatol. Jan 2009;60(1):168-9. [Medline].

  27. Knapp CF 3rd, Cooke ER, Sheehan DJ. Bullous fixed drug eruption caused by flecainide. J Am Acad Dermatol. Feb 2009;60(2):e3. [Medline].

  28. Ozkaya E, Mirzoyeva L, Jhaish MS. Ceftriaxone-induced fixed drug eruption: first report. Am J Clin Dermatol. 2008;9(5):345-7. [Medline].

  29. Fukushima S, Kidou M, Ihn H. Fixed food eruption caused by cashew nut. Allergol Int. Sep 2008;57(3):285-7. [Medline].

  30. Takahama H. A fixed drug eruption that developed cross-sensitivity among amide local anaesthetics, including mepivacaine hydrochloride, lidocaine hydrochloride and propitocaine hydrochloride. J Eur Acad Dermatol Venereol. Nov 2008;22(11):1400-1. [Medline].

  31. Bohm I, Medina J, Prieto P, Block W, Schild HH. Fixed drug eruption induced by an iodinated non-ionic X-ray contrast medium: a practical approach to identify the causative agent and to prevent its recurrence. Eur Radiol. Feb 2007;17(2):485-9. [Medline].

  32. Lammintausta K, Kortekangas-Savolainen O. Oral challenge in patients with suspected cutaneous adverse drug reactions: findings in 784 patients during a 25-year-period. Acta Derm Venereol. 2005;85(6):491-6. [Medline].

  33. Lammintausta K, Kortekangas-Savolainen O. The usefulness of skin tests to prove drug hypersensitivity. Br J Dermatol. May 2005;152(5):968-74. [Medline].

  34. Zedlitz S, Linzbach L, Kaufmann R, Boehncke WH. Reproducible identification of the causative drug of a fixed drug eruption by oral provocation and lesional patch testing. Contact Dermatitis. Jun 2002;46(6):352-3. [Medline].

  35. Kelso JM, Keating RM. Successful desensitization for treatment of a fixed drug eruption to allopurinol. J Allergy Clin Immunol. May 1996;97(5):1171-2. [Medline].

  36. Zawar V, Kirloskar M, Chuh A. Fixed drug eruption - a sexually inducible reaction?. Int J STD AIDS. Aug 2004;15(8):560-3. [Medline].

  37. Tornero P, De Barrio M, Baeza ML, Herrero T. Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing. Contact Dermatitis. Aug 2004;51(2):57-62. [Medline].

  38. Gonzalo-Garijo MA, de Argila D, Rodríguez-Nevado I. Generalized reaction after patch testing with metamizol. Contact Dermatitis. Sep 2001;45(3):180. [Medline].

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Further Reading

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Keywords

fixed drug eruption, fixed drug reaction, FDE, adverse drug reaction, adverse cutaneous drug reaction, drug-induced hypersensitivity, drug-induced pigmentation, postinflammatory hyperpigmentation, post-inflammatory hyperpigmentation

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Contributor Information and Disclosures

Author

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Jordan R Ilse, MD, Staff Physician, Scott and White Internal Medicine Residency Program, Temple, Texas
Jordan R Ilse, MD is a member of the following medical societies: American Medical Association and Texas Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Medicis Honoraria Consulting; Celgene Honoraria Consulting

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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