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).

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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).

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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

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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).

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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

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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; I serve on a safety monitoring committee for Principia Biopharma for: 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.