15/9/2019 https://emedicine.medscape.

com/article/1336702-print

emedicine.medscape.com

Fixed Drug Eruptions

Updated: Aug 12, 2019
Author: David F Butler, MD; Chief Editor: Dirk M Elston, MD

Overview

Background
The term fixed drug eruption (FDE) describes the development of one or more annular or oval erythematous patches as a
result of systemic exposure to a drug; these reactions normally resolve with hyperpigmentation and may recur at the same
site with reexposure to the drug. Repeated exposure to the offending drug may cause new lesions to develop in addition to
"lighting up" the older hyperpigmented lesions.

Adverse reactions to medications are common and often manifest as a cutaneous eruption. Drug-induced cutaneous
disorders frequently display a characteristic clinical morphology such as morbilliform exanthem, urticaria, hypersensitivity
syndrome, pseudolymphoma, photosensitivity, pigmentary changes, acute generalized exanthematous pustulosis, lichenoid
dermatitis, vasculitis, Stevens-Johnson syndrome, or fixed drug eruption.

Several variants of fixed drug eruption have been described, based on their clinical features and the distribution of the
lesions.[1, 2, 3, 4, 5, 6, 7] These include the following:

Pigmenting fixed drug eruption

Generalized or multiple fixed drug eruption

Linear fixed drug eruption

Wandering fixed drug eruption

Nonpigmenting fixed drug eruption

Bullous fixed drug eruption

Eczematous fixed drug eruption

Urticarial fixed drug eruption

Erythema dyschromicum perstans–like fixed drug eruption

Vulvitis

Oral

Psoriasiform

Cellulitislike eruption[8]

Also see the following related Medscape articles:

Drug Eruptions

Drug-Induced Bullous Disorders

Drug-Induced Gingival Hyperplasia

Drug-Induced Photosensitivity

Drug-Induced Pigmentation

Drug-Induced Pseudolymphoma Syndrome

https://emedicine.medscape.com/article/1336702-print 1/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Pathophysiology
Although the exact mechanism is unknown, recent research suggests a cell-mediated process that initiates both the active
and quiescent lesions. The process may involve an antibody-dependent, cell-mediated cytotoxic response.[9] CD8+
effector/memory T cells play an important role in reactivation of lesions with re-exposure to the offending drug.[10, 11]

The offending drug is thought to function as a hapten that preferentially binds to basal keratinocytes, leading to an
inflammatory response.[12] Through liberation of cytokines such as tumor necrosis factor-alpha, keratinocytes may locally
up-regulate expression of the intercellular adhesion molecule-1 (ICAM1).[13] The up-regulated ICAM1 has been shown to
help T cells (CD4 and CD8) migrate to the site of an insult.[14, 15]

The newly arriving and residential CD8 cells likely perpetuate tissue damage by their production of the inflammatory
cytokines interferon-gamma and tumor necrosis factor-alpha. CD8 cells isolated from active lesions have also been shown
to express alpha E beta 7, a ligand for E-cadherin, which may further contribute to the lymphocyte’s ability to localize to the
epidermis. Other cell surface molecules, such as CLA/alpha4beta1/CD4a, that bind E-selectin/vascular cellular adhesion
molecule-2/ICAM1 help to further attract CD8 cells to the area.[9]

Changes in cell surface markers allow vascular endothelium to select CD4 cells for migration into active lesions. These
regulatory CD4 cells likely produce interleukin 10, which has been shown to help suppress immune function, resulting in a
resting lesion.[9] As the inflammatory response dissipates, interleukin 15 expression from keratinocytes is thought to help
ensure the survival of CD8 cells, helping them fulfill their effector memory phenotypes. Thus, when reexposure to the drug
occurs, a more rapid response develops in the exact location of any prior lesions.[9]

Etiology
The major categories of causative agents of fixed drug eruption include antibiotics, antiepileptics, nonsteroidal anti-
inflammatory agents, sildenafil, and phenothiazines, although numerous other agents and certain foods such as cashews
and licorice have also been reported as causative agents. Ingestion of the causative agent may occur via any route,
including oral, rectal, or intravenous.[16, 17]

Certain classes of drugs with cross-reactions within a class have been reported to elicit a fixed drug eruption with
quinolones[18] and with nonsteroidal anti-inflammatory agents.[19] In some patients, the reaction may be to a dye rather
than the active ingredient.[20] Fixed drug eruption may rarely be related to foods, including residual antibiotics in meat
products and quinine contained in tonic water.[21, 22]

While fixed drug eruptions are uncommon with general anesthesia, propofol has been implicated in causing a drug eruption
on the penis.[23]

The most common cause is trimethoprim-sulfamethoxazole.[3, 24] Other substances implicated to cause fixed drug
eruptions are as follows[1, 12, 16, 25, 5, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36] :

Table. Substances Implicated in Fixed Drug Eruptions (Open Table in a new window)

Allylisopropyl- Amide local

Acetaminophen Acyclovir Allopurinol
acetylurea anesthetics

Amlexanox Amoxicillin Anticonvulsants Articaine Aspirin

Atenolol Barbiturates Botulinum toxin Carbamazepine Cashew nut

Ceftriaxone Celecoxib Cetirizine Chloral hydrate Chlordiazepoxide

https://emedicine.medscape.com/article/1336702-print 2/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Chlorhexidine Chlormezanone Chlorphenesin Citicoline Clarithromycin

carbonate

Clioquinol Clopidogrel Codeine Colchicines Cyclizine

Cyproterone acetate Dextromethorphan Dimenhydrinate Diphenhydramine Dipyrone

Eperisone
Docetaxel Erythromycin Ethenzamide Feprazone
hydrochloride

Finasteride Flecainide Fluconazole Fluoroquinolones Foscarnet

Gabapentin Griseofulvin Hydroxyzine Ibuprofen Interferon

Iodinated radiography
Iomeprol Kakkon Ketoconazole Lactose
contrast media

Liquorice
Lamotrigine Lentils Lopamidoln Loratadine
Lomeprol

Magnesium
Lormetazepam Mefenamic acid Melatonin Methaqualone
trisilicate

Metramizole Metronidazole Metaform Minocycline Multivitamins

Naproxen Nimesulide Omeprazole Ondansetron Opium alkaloids

Para-
Oxyphenbutazone Paclitaxel Pamabrom Papaverine aminosalicylic
acid

Penicillins Phenazone Phenolphthalein Phenylbutazone Phenylephrine

Phenylpropanolamine Phenytoin Pipemidic acid Piroxicam Procarbazine

https://emedicine.medscape.com/article/1336702-print 3/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Prochlorperazine Pseudoephedrine Quinine Rifampin Scopolia

Sodium benzoate Strawberries Sulfamethoxazole Tartrazine Terbinafine

Tetracyclines Theophylline Thiacetazone Ticlopidine Tinidazole

Tolfenamic acid Tosufloxacin Tranexamic acid Trimethoprim Tropisetron

Epidemiology
Frequency

United States

The prevalence of drug eruptions has been reported to range from 2-5% for inpatients and greater than 1% for outpatients.
[37] Fixed drug eruptions may account for as much as 16-21% of all cutaneous drug eruptions. The actual frequency may
be higher than current estimates, owing to the availability of a variety of over-the-counter medications and nutritional
supplements that are known to elicit fixed drug eruptions.

International

The international prevalence is variable but is likely similar to that in the United States. Most studies report fixed drug
eruptions to be the second or third most common skin manifestation of adverse drug events.[38]

Race
Fixed drug eruptions have no known racial predilection. A genetic susceptibility to developing a fixed drug eruption with an
increased incidence of HLA-B22 is possible.[39, 40]

Sex

One large study of 450 patients revealed a male-to-female ratio of 1:1.1 for fixed drug eruptions.[1]

Age

Fixed drug eruptions have been reported in patients as young as 1.5 years and as old as 87 years. The mean age at
presentation is 30.4 years in males and 31.3 years in females.[1]

Prognosis
The prognosis is very good, and an uneventful recovery should be expected. No deaths due to fixed drug eruption have
been reported. Residual hyperpigmentation is very common, but this is less likely with the nonpigmenting variant.

Widespread lesions may initially mimic toxic epidermal necrolysis, but they have a benign clinical course.[41] Again,
localized hyperpigmentation is a common complication, but pain, infection, and, rarely, hypopigmentation, also may occur.[1]

Patient Education
https://emedicine.medscape.com/article/1336702-print 4/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Patients should be counseled on medication avoidance and possible cross-reactions of similar medications. Patients should
notify their physicians of all drug allergies they have experienced.

Presentation

History
The initial eruption is often solitary and frequently located on the lip or genitalia. Rarely, the eruption may be intraoral. Other
common locations of the initial lesion are the hip, lower back/sacrum, or proximal extremity. With the initial fixed drug
eruption attack, a delay of up to 2 weeks may occur from the initial exposure to the drug to the development of the skin
lesion.[42] Skin lesions develop over a period of hours but require days to become necrotic. Lesions may persist from days
to weeks and then fade slowly to residual oval hyperpigmented patches.

Subsequent reexposure to the medication results in a reactivation of the site, with inflammation occurring within 30 minutes
to 16 hours.[43] The reactivation of old lesions also may be associated with the development of new lesions at other sites.

Patients may not be cognizant that a drug, nutritional supplement, over-the-counter medication, or, rarely, food (eg, fruits,
nuts) triggered the skin problem. They may be convinced that an insect, particularly a spider, may be the culprit. A careful
history is required to elicit the fact that a drug has been taken and is temporally related to the onset of the eruption.
Medications taken episodically, such as pain relievers, antibiotics, or laxatives, are often to blame. When able to be
identified, patients often report ingestion of one the following types of medications[16] :

Analgesics

Muscle relaxants

Sedatives

Anticonvulsants

Antibiotics

Local symptoms may include pruritus, burning, and pain.[1] Systemic symptoms are uncommon, but fever, malaise, nausea,
diarrhea, abdominal cramps, anorexia, and dysuria have been reported.[43, 16]

Further questioning may reveal prior episodes of fixed drug eruption, atopic disease, or other past drug reactions. Family
history may render a history of atopy, drug reactions, or diabetes mellitus.[1]

Several cases of fixed drug eruption on the genitalia have been reported in patients who were not ingesting the drug but
whose sexual partner was taking the offending drug and the patient was exposed to the drug through sexual contact.[44, 45,
46]

Physical Examination
The most common clinical manifestation is the pigmenting fixed drug eruption, which usually manifests as round or oval,
sharply demarcated erythematous/edematous plaques located on the lip, hip, sacrum, or genitalia.[2] These erythematous
patches or plaques gradually fade with residual hyperpigmentation (see images below). The center of the patch may blister
or become necrotic. Other less common variants may manifest as lesions resembling erythema multiforme, toxic epidermal
necrolysis, eczema, urticaria, a linear pattern following Blaschko lines, bullous lesions, a migrating eruption, or a
nonpigmenting form with no postinflammatory hyperpigmentation.[3] Pseudoephedrine,[47] piroxicam,[48] cotrimoxazole,
[49] sorafenib,[50] and tadalafil[51] have all been reported to cause the nonpigmenting form of this condition.

https://emedicine.medscape.com/article/1336702-print 5/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Targetoid fixed drug eruption on the abdomen of a child.

Hyperpigmented fixed drug eruption on the hip of an adult.

https://emedicine.medscape.com/article/1336702-print 6/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Vesicular fixed drug eruption on the glans penis.

Multiple hyperpigmented fixed drug eruptions on the trunk.

https://emedicine.medscape.com/article/1336702-print 7/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Hyperpigmented fixed drug eruption on the right side of the upper lip.

Initially, a single lesion or a few lesions develop, but, with reexposure, additional lesions occur. The vast majority of patients
present with 1-30 lesions, ranging in size of 0.5-5 cm, but reports of lesions greater than 10 cm have been published.
Lesions may be generalized. The most common reported site is the lips, and these may be seen in up to half of all cases.[1]

Medications may also follow a site-specific eruption pattern. For example, trimethoprim-sulfamethoxazole (Bactrim) has
been shown to favor the genital region (especially in males) and naproxen and the oxicams involve the lips.[2]

Resting/inactive lesions tend to appear as round or oval, gray, hyperpigmented macules.

Upon reexposure, the resting hyperpigmented macules activate, developing a violaceous center encircled by concentric
rings of erythema. Re-administration of the medication poses the risk of increased pigmentation, size, and number of
lesions.

Individuals with darker pigmentation may develop postinflammatory hypopigmented macules once the lesions have
resolved.[12]

Complications
Hyperpigmentation is the most likely complication of a fixed drug eruption (FDE). The potential for infection exists in the
setting of multiple, eroded lesions. Generalized eruptions have been reported following topical and oral provocation testing.
[16, 52]

DDx

Differential Diagnoses
Acute Urticaria

Bullous Pemphigoid

Cellulitis

Dermatologic Manifestations of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Discoid Lupus Erythematosus

https://emedicine.medscape.com/article/1336702-print 8/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Drug Eruptions

Drug-Induced Bullous Disorders

Drug-Induced Pemphigus

Eczema

Erythema Annulare Centrifugum

Erythema Dyschromicum Perstans

Erythema Multiforme

Herpes Simplex

Insect Bites

Lichen Planus

Lichen Planus Actinicus

Melasma

Pemphigus Vulgaris

Pityriasis Rosea

Postinflammatory Hyperpigmentation

Psoriasis

Workup

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
Patch testing and oral provocation have been used to identify the suspected agent and check for cross-sensitivities to
medications.[53, 54, 55, 56] 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.[57] Patch testing must be performed on a previously involved site;
otherwise, a false-negative result is likely.[54] 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.[58]

Procedures
Skin biopsy is the diagnostic procedure of choice.

https://emedicine.medscape.com/article/1336702-print 9/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

Histologic Findings
Histological examination of inflammatory/acute lesions shows an interface dermatitis with vacuolar change and Civatte
bodies[12] (see the image below).

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

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).

https://emedicine.medscape.com/article/1336702-print 10/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

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

Medical Care
The main goal of treatment is to identify the causative agent and avoid it. Treatment for fixed drug eruptions (FDEs)
otherwise is symptomatic. Systemic antihistamines and topical corticosteroids may be all that are required. In cases in which
infection is suspected, antibiotics and proper wound care are advised. Desensitization to medications has been reported in
the literature, but this should be avoided unless no substitutes exist.[59] In severe cases, cyclosporine has been used.[60]

Consultations
Consultation with a dermatologist is warranted if the diagnosis is in doubt. If patch testing is needed to determine which drug
may be involved, a dermatologist with such experience may be required. If Stevens-Johnson syndrome or toxic epidermal
necrolysis is suspected, hospitalization and possible referral to the intensive care unit or burn unit may be appropriate.

Diet
A regular diet is usually acceptable. However, food may be an exacerbating factor; reactivation has been reported with
cashews, liquorice, lentils, and strawberries.[12, 30, 33]

Activity
Generally, no limits on activities are imposed. Multiple studies have sited male genital lesions occurring following intercourse
with female partners taking trimethoprim-sulfamethoxazole.[61] Therefore, patients may consider avoiding sexual activity
while a partner is taking a medication that has resulted in a prior fixed drug eruption. If open lesions are present, general
wound care precautions are recommended.

Prevention
Avoid the offending drug. Patch testing may be used to help identify agents that pose a risk of cross-sensitivity.[62]

Medication

Medication Summary
Lesions of fixed drug eruption resolve spontaneously with avoidance of the inciting drug. Additional medications should be
used to relieve symptoms associated with the condition. Generally, an oral antihistamine (eg, hydroxyzine) and a topical

https://emedicine.medscape.com/article/1336702-print 11/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

corticosteroid may be sufficient. The use of corticosteroids may interfere with later diagnostic provocation testing.
Hyperpigmentation may take many months to resolve. Incontinent pigment in the dermis responds poorly to topical
bleaching agents such as hydroquinones.

Questions & Answers

Overview

What is a fixed drug eruption (FDE)?

What are the variants of fixed drug eruptions (FDE)?

What is the pathophysiology of fixed drug eruptions (FDE)?

What are causative agents of fixed drug eruptions (FDE)?

How common are fixed drug eruptions (FDE) in the US?

What is the international prevalence of fixed drug eruptions (FDE)?

Do fixed drug eruptions (FDE) have a racial predilection?

What are the sex-related demographics of fixed drug eruptions (FDE)?

What are the age-related demographics of fixed drug eruptions (FDE)?

What is the prognosis of fixed drug eruption (FDE)?

What is involved in patient education for fixed drug eruptions (FDE)?

Presentation

What is the clinical history of fixed drug eruptions (FDE)?

Which medications are associated with fixed drug eruptions (FDE)?

What are the symptoms of fixed drug eruptions (FDE)?

What is the clinical manifestation of fixed drug eruption (FDE)?

What are common physical findings of fixed drug eruptions (FDE)?

What are the complications of fixed drug eruptions (FDE)?

DDX

What are the differential diagnoses for Fixed Drug Eruptions?

Workup

Are blood studies useful in the workup of fixed drug eruptions (FDE)?

What other tests are indicated in the workup of fixed drug eruptions (FDE)?

What is the diagnostic procedure of choice for fixed drug eruptions (FDE)?

What are histologic findings of fixed drug eruptions (FDE)?

Treatment

What is the main goal of treatment for fixed drug eruptions (FDE)?

Which specialist consultations are recommended in the treatment of fixed drug eruptions (FDE)?

What dietary recommendations are indicated in the treatment of fixed drug eruptions (FDE)?

Should activity be restricted in the treatment of fixed drug eruptions (FDE)?

What is involved in the prevention of fixed drug eruptions (FDE)?

Medications

https://emedicine.medscape.com/article/1336702-print 12/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print

What is the medical therapy for fixed drug eruptions (FDE)?

Contributor Information and Disclosures

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, American Society for MOHS Surgery, Association of Military Dermatologists, Phi Beta Kappa

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 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 i inherited these trust accounts; for: Allergen; Celgene; Pfizer; 3M; Johnson and Johnson;
Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

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, Pediatrics, Medicine, and
Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University
School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of
Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

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.

References

https://emedicine.medscape.com/article/1336702-print 13/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print
1. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol. 1998 Nov. 37(11):833-8. [Medline].

2. Ozkaya-Bayazit E. Specific site involvement in fixed drug eruption. J Am Acad Dermatol. 2003 Dec. 49(6):1003-7. [Medline].

3. Ozkaya-Bayazit E, Bayazit H, Ozarmagan G. Drug related clinical pattern in fixed drug eruption. Eur J Dermatol. 2000 Jun.
10(4):288-91. [Medline].

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

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

6. Katoulis AC, Bozi E, Kanelleas A, et al. Psoriasiform fixed drug eruption caused by nimesulide. Clin Exp Dermatol. 2009 Oct.
34(7):e360-1. [Medline].

7. Srivastava R, Bihari M, Bhuvan J, Saad A. Fixed drug eruptions with intraoral presentation. Indian J Dent. 2015 Apr-Jun. 6
(2):103-6. [Medline].

8. 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. [Medline]. [Full Text].

9. 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. [Medline].

10. 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. [Medline].

11. Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol. 2009 Aug. 9(4):316-21.
[Medline].

12. Weedon D. The lichenoid reaction pattern ('interface dermatitis'). Skin Pathology. 2nd ed. London, England: Churchill
Livingstone; 2002. 42-43.

13. 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. [Medline].

14. 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. [Medline].

15. 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. [Medline].

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

17. 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. [Medline].

18. 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.
[Medline].

19. 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.
[Medline].

20. 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. [Medline].

21. 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. [Medline]. [Full Text].

22. 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. [Medline].

23. Allchurch LG, Crilly H. Fixed drug eruption to propofol. Anaesth Intensive Care. 2014 Nov. 42 (6):777-81. [Medline].

24. 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. [Medline].

25. 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].

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

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

https://emedicine.medscape.com/article/1336702-print 14/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print
28. Knapp CF 3rd, Cooke ER, Sheehan DJ. Bullous fixed drug eruption caused by flecainide. J Am Acad Dermatol. 2009 Feb.
60(2):e3. [Medline].

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

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

31. 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.
[Medline].

32. 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. [Medline].

33. 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. [Medline].

34. Orellana-Barrios M, Medrano Juarez R, Patel NJ. Fixed drug eruption associated with aspirin. BMJ Case Rep. 2018 Mar 17.
2018:[Medline].

35. 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. [Medline].

36. 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. [Medline].

37. 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. [Medline].

38. Lee AY. Fixed drug eruptions. Incidence, recognition, and avoidance. Am J Clin Dermatol. 2000 Sep-Oct. 1(5):277-85. [Medline].

39. 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. [Medline].

40. 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. [Medline].

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

42. Bolognia JL, Jorizzo JL, Rapini RP. Fixed drug eruptions. Dermatology. London, England: Mosby; 2003. 344-5.

43. 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.

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

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

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

47. 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. [Medline].

48. 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. [Medline].

49. Rasi A, Khatami A. Unilateral non-pigmenting fixed drug eruption associated with cotrimoxazole. Dermatol Online J. 2006 Oct
31. 12 (6):12. [Medline].

50. 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. [Medline].

51. 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. [Medline].

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

53. 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].

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

https://emedicine.medscape.com/article/1336702-print 15/16
15/9/2019 https://emedicine.medscape.com/article/1336702-print
55. 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. [Medline].

56. 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. [Medline].

57. 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. [Medline].

58. Andrade P, Brinca A, Gonçalo M. Patch testing in fixed drug eruptions--a 20-year review. Contact Dermatitis. 2011 Oct.
65(4):195-201. [Medline].

59. 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. [Medline].

60. Malviya N, Cyrus N, Vandergriff T, Mauskar M. Generalized bullous fixed drug eruption treated with cyclosporine. Dermatol
Online J. 2017 Feb 15. 23 (2):[Medline].

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

62. 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. [Medline].

https://emedicine.medscape.com/article/1336702-print 16/16