Laboratory Studies

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

Other Tests

Patch testing and oral provocation have been used to identify the suspected agent and check for cross-sensitivities to medications.^{[58, 59, 60, 61]}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.^[62]Patch testing must be performed on a previously involved site; otherwise, a false-negative result is likely.^[59]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.

Patch testing is particularly efficacious in identifying a putative cause of the reaction when nonsteroidal anti-inflammatory agents are suspected, but patch testing is not helpful in discerning reactions to antibiotics and allopurinol.^[63]

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 bodies^[13](see the image below).

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

View Media Gallery

The overall pattern may mimic that seen in erythema multiforme. Dyskeratosis and individual necrotic keratinocytes within the epidermis may be a prominent feature (see the image below).

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

View Media Gallery

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.

Treatment & Management

Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol. 1998 Nov. 37(11):833-8. [QxMD MEDLINE Link].
Ozkaya-Bayazit E. Specific site involvement in fixed drug eruption. J Am Acad Dermatol. 2003 Dec. 49(6):1003-7. [QxMD MEDLINE Link].
Ozkaya-Bayazit E, Bayazit H, Ozarmagan G. Drug related clinical pattern in fixed drug eruption. Eur J Dermatol. 2000 Jun. 10(4):288-91. [QxMD MEDLINE Link].
Fischer G. Vulvar fixed drug eruption. A report of 13 cases. J Reprod Med. 2007 Feb. 52(2):81-6. [QxMD MEDLINE Link].
Gupta S, Gupta S, Mittal A, David S. Oral fixed drug eruption caused by gabapentin. J Eur Acad Dermatol Venereol. 2009 Feb 19. [QxMD MEDLINE Link].
Katoulis AC, Bozi E, Kanelleas A, et al. Psoriasiform fixed drug eruption caused by nimesulide. Clin Exp Dermatol. 2009 Oct. 34(7):e360-1. [QxMD MEDLINE Link].
Srivastava R, Bihari M, Bhuvan J, Saad A. Fixed drug eruptions with intraoral presentation. Indian J Dent. 2015 Apr-Jun. 6 (2):103-6. [QxMD MEDLINE Link].
Patel S, John AM, Handler MZ, Schwartz RA. Fixed Drug Eruptions: An Update, Emphasizing the Potentially Lethal Generalized Bullous Fixed Drug Eruption. Am J Clin Dermatol. 2020 Jun. 21 (3):393-399. [QxMD MEDLINE Link].
Fathallah N, Ben Salem C, Slim R, Boussofara L, Ghariani N, Bouraoui K. Acetaminophen-induced cellulitis-like fixed drug eruption. Indian J Dermatol. 2011 Mar. 56(2):206-8. [QxMD MEDLINE Link]. [Full Text].
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 Sep. 112(3):609-15. [QxMD MEDLINE Link].
Mizukawa Y, Shiohara T. Fixed drug eruption: a prototypic disorder mediated by effector memory T cells. Curr Allergy Asthma Rep. 2009 Jan. 9(1):71-7. [QxMD MEDLINE Link].
Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol. 2009 Aug. 9(4):316-21. [QxMD MEDLINE Link].
Weedon D. The lichenoid reaction pattern ('interface dermatitis'). Skin Pathology. 2nd ed. London, England: Churchill Livingstone; 2002. 42-43.
Smoller BR, Luster AD, Krane JF, et al. Fixed drug eruptions: evidence for a cytokine-mediated process. J Cutan Pathol. 1991 Feb. 18(1):13-9. [QxMD MEDLINE Link].
Hindsen M, Christensen OB, Gruic V, Lofberg H. Fixed drug eruption: an immunohistochemical investigation of the acute and healing phase. Br J Dermatol. 1987 Mar. 116(3):351-60. [QxMD MEDLINE Link].
Shiohara T, Nickoloff BJ, Sagawa Y, Gomi T, Nagashima M. Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1). Arch Dermatol. 1989 Oct. 125(10):1371-6. [QxMD MEDLINE Link].
Sehgal VN, Srivastava G. Fixed drug eruption (FDE): changing scenario of incriminating drugs. Int J Dermatol. 2006 Aug. 45(8):897-908. [QxMD MEDLINE Link].
Choi SY, Suh JH, Park KY, Li K, Kim BJ, Seo SJ, et al. Fixed Drug Eruption Caused by Sildenafil Citrate. Ann Dermatol. 2017 Apr. 29 (2):247-248. [QxMD MEDLINE Link].
Sánchez-Morillas L, Rojas Pérez-Ezquerra P, González Morales ML, Mayorga C, González-Mendiola R, Laguna Martínez JJ. Fixed drug eruption due to norfloxacin and cross-reactivity with other quinolones. Allergol Immunopathol (Madr). 2012 Jan 20. [QxMD MEDLINE Link].
Pérez-Calderón R, Gonzalo-Garijo MA, Pérez-Rangel I, Sánchez-Vega S, Zambonino MA. Fixed drug eruption due to nabumetone in a patient with previous fixed drug eruptions due to naproxen. J Investig Allergol Clin Immunol. 2011. 21(2):153-4. [QxMD MEDLINE Link].
Leleu C, Boulitrop C, Bel B, Jeudy G, Vabres P, Collet E. Quinoline Yellow dye-induced fixed food-and-drug eruption. Contact Dermatitis. 2013 Mar. 68(3):187-8. [QxMD MEDLINE Link].
Lim WS, Kim DH, Jin SY, Choi YS, Lee SH, Huh HJ, et al. A case of fixed drug eruption due to doxycycline and erythromycin present in food. Allergy Asthma Immunol Res. 2013 Sep. 5(5):337-9. [QxMD MEDLINE Link]. [Full Text].
Ohira A, Yamaguchi S, Miyagi T, et al. Fixed eruption due to quinine in tonic water: a case report with high-performance liquid chromatography and ultraviolet A analyses. J Dermatol. 2013 Aug. 40(8):629-31. [QxMD MEDLINE Link].
Allchurch LG, Crilly H. Fixed drug eruption to propofol. Anaesth Intensive Care. 2014 Nov. 42 (6):777-81. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Fixed drug eruption associated with sulfonamides sold in Latino grocery stores - Greater Washington, DC, area, 2012-2013. MMWR Morb Mortal Wkly Rep. 2013 Nov 22. 62(46):914-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ghosh SK, Bandyopadhyay D. Clopidogrel-induced fixed drug eruption. J Eur Acad Dermatol Venereol. 2009 Jan 20. [QxMD MEDLINE Link].
Oyama N, Kaneko F. Solitary fixed drug eruption caused by finasteride. J Am Acad Dermatol. 2009 Jan. 60(1):168-9. [QxMD MEDLINE Link].
Knapp CF 3rd, Cooke ER, Sheehan DJ. Bullous fixed drug eruption caused by flecainide. J Am Acad Dermatol. 2009 Feb. 60(2):e3. [QxMD MEDLINE Link].
Ozkaya E, Mirzoyeva L, Jhaish MS. Ceftriaxone-induced fixed drug eruption: first report. Am J Clin Dermatol. 2008. 9(5):345-7. [QxMD MEDLINE Link].
Fukushima S, Kidou M, Ihn H. Fixed food eruption caused by cashew nut. Allergol Int. 2008 Sep. 57(3):285-7. [QxMD MEDLINE Link].
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. 2008 Nov. 22(11):1400-1. [QxMD MEDLINE Link].
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. 2007 Feb. 17(2):485-9. [QxMD MEDLINE Link].
Benomar S, Ismaili N, Koufane J, Senouci K, Hassam B. [Fixed food eruption caused by liquorice.]. Ann Dermatol Venereol. 2010 Feb. 137(2):121-123. [QxMD MEDLINE Link].
Orellana-Barrios M, Medrano Juarez R, Patel NJ. Fixed drug eruption associated with aspirin. BMJ Case Rep. 2018 Mar 17. 2018:[QxMD MEDLINE Link].
Zaouak A, Ben Brahim E, Ben Tanfous A, Koubaa W, Sahnoun R, Hammami H, et al. Mucosal fixed drug eruption due to mefenamic acid: Report of a case and a review. Therapie. 2018 Feb 15. [QxMD MEDLINE Link].
Özkaya E. Changing trends in inducer drugs of fixed drug eruption: a 20-year cross-sectional study from Turkey. J Dtsch Dermatol Ges. 2018 Apr. 16 (4):474-476. [QxMD MEDLINE Link].
Sharma L, Agarwal R, Chopra A, Mitra B. A Cross-Sectional Observational Study of Clinical Spectrum and Prevalence of Fixed Food Eruption in a Tertiary Care Hospital. Indian Dermatol Online J. 2020 May-Jun. 11 (3):361-366. [QxMD MEDLINE Link].
Martínez Antón MD, Galán Gimeno C, Sánchez de Vicente J, Jáuregui Presa I, Gamboa Setién PM. Etoricoxib-induced fixed drug eruption: Report of seven cases. Contact Dermatitis. 2020 Jul 15. [QxMD MEDLINE Link].
Gupta S, Gupta S, Mahendra A, Yadav A. Multiple widespread fixed drug eruption caused by rabeprazole. J Postgrad Med. 2020 Apr-Jun. 66 (2):105-107. [QxMD MEDLINE Link].
Kepil Özdemir S, Bavbek S. Hypersensitivity reactions to proton-pump inhibitors: Clinical presentation, diagnosis, and management. Allergy Asthma Proc. 2020 Mar 1. 41 (2):e37-e44. [QxMD MEDLINE Link].
Krahenbuhl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krahenbuhl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf. 2007. 30(5):379-407. [QxMD MEDLINE Link].
Lee AY. Fixed drug eruptions. Incidence, recognition, and avoidance. Am J Clin Dermatol. 2000 Sep-Oct. 1(5):277-85. [QxMD MEDLINE Link].
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. 1994 Jan. 30(1):52-4. [QxMD MEDLINE Link].
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. 1997 May. 36(5 Pt 1):782-4. [QxMD MEDLINE Link].
Baird BJ, De Villez RL. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol. 1988 Apr. 27(3):170-4. [QxMD MEDLINE Link].
Bolognia JL, Jorizzo JL, Rapini RP. Fixed drug eruptions. Dermatology. London, England: Mosby; 2003. 344-5.
Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI. Fixed drug eruptions. Fitzpatrick’s Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill; 2003. 1333.
Zawar V, Chuh A. Fixed drug reaction may be sexually induced. Int J Dermatol. 2006 Aug. 45(8):1003-4; author reply 1004. [QxMD MEDLINE Link].
Berger RE. Fixed drug eruption--a sexually inducible reaction?. J Urol. 2005 Jun. 173(6):1990. [QxMD MEDLINE Link].
Zawar V, Kirloskar M, Chuh A. Fixed drug eruption - a sexually inducible reaction?. Int J STD AIDS. 2004 Aug. 15(8):560-3. [QxMD MEDLINE Link].
Vidal C, Prieto A, Pérez-Carral C, Armisén M. Nonpigmenting fixed drug eruption due to pseudoephedrine. Ann Allergy Asthma Immunol. 1998 Apr. 80 (4):309-10. [QxMD MEDLINE Link].
Montoro J, Díaz M, Genís C, Lozano A, Bertomeu F. Non-pigmenting cutaneous-mucosal fixed drug eruption due to piroxicam. Allergol Immunopathol (Madr). 2003 Jan-Feb. 31 (1):53-5. [QxMD MEDLINE Link].
Rasi A, Khatami A. Unilateral non-pigmenting fixed drug eruption associated with cotrimoxazole. Dermatol Online J. 2006 Oct 31. 12 (6):12. [QxMD MEDLINE Link].
Tanabe K, Amoh Y, Mii S, Eto H, Iwamura M, Katsuoka K. Non-pigmenting fixed drug eruption induced by sorafenib. Acta Derm Venereol. 2010 May. 90 (3):307. [QxMD MEDLINE Link].
Das S, Das S, Chowdhury J, Bhanja DC. Non pigmenting mucosal fixed drug eruption due to tadalafil: A report of two cases. Indian Dermatol Online J. 2014 Apr. 5 (2):167-9. [QxMD MEDLINE Link].
Gonzalo-Garijo MA, de Argila D, Rodriguez-Nevado I. Generalized reaction after patch testing with metamizol. Contact Dermatitis. 2001 Sep. 45(3):180. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Lammintausta K, Kortekangas-Savolainen O. The usefulness of skin tests to prove drug hypersensitivity. Br J Dermatol. 2005 May. 152(5):968-74. [QxMD MEDLINE Link].
Li PH, Watts TJ, Chung HY, Lau CS. Fixed Drug Eruption to Biologics and Role of Lesional Patch Testing. J Allergy Clin Immunol Pract. 2019 Jul 17. [QxMD MEDLINE Link].
Ben Fadhel N, Chaabane A, Ammar H, Ben Romdhane H, Soua Y, Chadli Z, et al. Clinical features, culprit drugs, and allergology workup in 41 cases of fixed drug eruption. Contact Dermatitis. 2019 Jul 10. [QxMD MEDLINE Link].
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. 2002 Jun. 46(6):352-3. [QxMD MEDLINE Link].
Andrade P, Brinca A, Gonçalo M. Patch testing in fixed drug eruptions--a 20-year review. Contact Dermatitis. 2011 Oct. 65(4):195-201. [QxMD MEDLINE Link].
Kelso JM, Keating RM. Successful desensitization for treatment of a fixed drug eruption to allopurinol. J Allergy Clin Immunol. 1996 May. 97(5):1171-2. [QxMD MEDLINE Link].
Malviya N, Cyrus N, Vandergriff T, Mauskar M. Generalized bullous fixed drug eruption treated with cyclosporine. Dermatol Online J. 2017 Feb 15. 23 (2):[QxMD MEDLINE Link].
Zawar V, Kirloskar M, Chuh A. Fixed drug eruption - a sexually inducible reaction?. Int J STD AIDS. 2004 Aug. 15(8):560-3. [QxMD MEDLINE Link].
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. 2004 Aug. 51(2):57-62. [QxMD MEDLINE Link].

Media Gallery

Targetoid fixed drug eruption on the abdomen of a child.
Hyperpigmented fixed drug eruption on the hip of an adult.
Vesicular fixed drug eruption on the glans penis.
Multiple hyperpigmented fixed drug eruptions on the trunk.
Hyperpigmented fixed drug eruption on the right side of the upper lip.
Acute interface dermatitis with prominent vacuolar change and individual necrotic keratinocytes within the epidermis (X10).
Interface dermatitis, vacuolar change, necrotic keratinocytes, and incontinent pigment in the dermis (X40).

of 7

Table. Substances Implicated in Fixed Drug Eruptions

Table. Substances Implicated in Fixed Drug Eruptions

Acetaminophen	Acyclovir	Allopurinol	Allylisopropyl-acetylurea	Amide local anesthetics
Amlexanox	Amoxicillin	Anticonvulsants	Articaine	Aspirin
Atenolol	Barbiturates	Botulinum toxin	Carbamazepine	Cashew nut
Ceftriaxone	Celecoxib	Cetirizine	Chloral hydrate	Chlordiazepoxide
Chlorhexidine	Chlormezanone	Chlorphenesin carbonate	Citicoline	Clarithromycin
Clioquinol	Clopidogrel	Codeine	Colchicines	Cyclizine
Cyproterone acetate	Dextromethorphan	Dimenhydrinate	Diphenhydramine	Dipyrone
Docetaxel	Eperisone hydrochloride	Erythromycin	Ethenzamide	Feprazone
Finasteride	Flecainide	Fluconazole	Fluoroquinolones	Foscarnet
Gabapentin	Griseofulvin	Hydroxyzine	Ibuprofen	Interferon
Iodinated radiography contrast media	Iomeprol	Kakkon	Ketoconazole	Lactose
Lamotrigine	Lentils	Liquorice Lomeprol	Lopamidoln	Loratadine
Lormetazepam	Magnesium trisilicate	Mefenamic acid	Melatonin	Methaqualone
Metramizole	Metronidazole	Metaform	Minocycline	Multivitamins
Naproxen	Nimesulide	Omeprazole	Ondansetron	Opium alkaloids
Oxyphenbutazone	Paclitaxel	Pamabrom	Papaverine	Para-aminosalicylic acid
Penicillins	Phenazone	Phenolphthalein	Phenylbutazone	Phenylephrine
Phenylpropanolamine	Phenytoin	Pipemidic acid	Piroxicam	Procarbazine
Prochlorperazine	Pseudoephedrine	Quinine	Rifampin	Scopolia
Sodium benzoate	Strawberries	Sulfamethoxazole	Tartrazine	Terbinafine
Tetracyclines	Theophylline	Thiacetazone	Ticlopidine	Tinidazole
Tolfenamic acid	Tosufloxacin	Tranexamic acid	Trimethoprim	Tropisetron

Back to List

Author

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster 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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), 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, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Genentech as a consultant for a potential study on a drug that has yet to be approved for any use<br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts; I served on a safety monitoring committee for Principia Biopharma (ended 9-2021) for: Stocks held in various trust accounts: Allergen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen; Gilead.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Acknowledgements

Jordan R Ilse, MD Staff Physician, Scott and White Internal Medicine Residency Program, Scott and White Clinic, Texas A&M University College of Medicine

Jordan R Ilse, MD is a member of the following medical societies: American Medical Association and Texas Medical Association

Disclosure: Nothing to disclose.