A 79-year-old Caucasian man with a history of chest pain, light-headedness, and diaphoresis was admitted to rule out acute coronary syndrome. He incidentally noted a bruise that had appeared spontaneously on his chest without trauma four days prior to admission. The patient's history included supraventricular tachycardia for which he had recently undergone ablation therapy. He had been taking aspirin 81 mg daily for years but was not taking warfarin (Coumadin) or any other anticoagulation medications. A few weeks prior to symptom onset, he had started taking naproxen (Naprosyn, Anaprox).
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Fixed drug eruption
The diagnosis was fixed drug eruption (FDE) induced by naproxen. FDE is defined as a peculiar onset of round or oval, edematous, dusky red macules or plaques on the skin and/or mucous membranes.
Our patient had a circumscribed, well-demarcated, violaceous 8- × 3-cm plaque with central hypopigmentation located just medial and inferior to the left nipple. In some patients, the lesions can be accompanied by burning or itching.1,2
The characteristics of the lesion were first described by Bourns in 1889, with antipyrine as the causative agent, but the term “fixed drug eruption” is attributed to Brocq. Although exact pathophysiologic mechanisms remain unclear, histopathology typically demonstrates a superficial and deep dermal and perivascular infiltrate of lymphocytes, eosinophils, neutrophils, and dermal macrophages pigmented with melanin (melanophages).3 Diagnosis can be elusive, as the incubation period from medication initiation to disease presentation can be weeks to years.4
The medical literature is replete with drugs causing FDE. Some of the more common agents include antimicrobials (tetracycline, sulfa derivatives, metronidazole), anti-inflammatory agents (nonsteroidal anti-inflammatory drugs, salicyclates), psychoactive agents (barbiturates), oral contraceptives, quinine (including quinine in tonic water), phenolphthalein, and food coloring (in food or medications).5
Systemic provocation testing can be pursued for further evaluation. This is typically performed by administering the offending agent in subtherapeutic doses that are increased gradually, such as an initial dose of one-eighth tablet increased every 12-24 hours to a whole tablet.6 Flare reactions can be seen within 10-30 minutes or up to 18 hours after testing.7 Lack of standardization makes testing problematic, but topical provocation testing involves skin-patch testing with the culprit drug to evoke a response. Positive reactions typically occur at the site of previously involved skin.7
Treatment of FDE primarily focuses on avoiding the offending agent. Additional treatment options include topical corticosteroids for mild lesions; wet compresses or antimicrobial ointment, such as bacitracin, for erosive lesions; and systemic steroids for severe generalized bullous lesions.5 Skin changes, such as post-inflammatory hyperpigmentation, generally spontaneously resolve within weeks of drug withdrawal but may recur within hours of repeat exposure. 3
This patient was educated on the cause of his rash and instructed to discontinue the daily use of naproxen. The rash was noted to be resolving on follow-up evaluation a few days after discharge and had resolved completely within two weeks. In the absence of additional naproxen use, there has been no recurrence.
Dr. Simon is in the Family Medicine Residency program at the Mayo Clinic in Scottsdale, Ariz.
References
1. Sehgal V, Gangwani O. Fixed drug eruption. Current concepts. Int J Dermatol. 1987;26:67-74.
2. Nigen S, Knowles SR, Shear NH. Drug eruptions: approaching the diagnosis of drug-induced skin diseases. J Drugs Dermatol. 2003;2:278-299.
3. Valeyrie-Allanore L, Sassolas B, Rojeau JC. Drug-induced skin, nail and hair disorders. Drug Saf. 2007;30:1011-1030.
4. Sehgal VN, Srivastava G. Fixed drug eruption (FDE): changing scenario of incriminating drugs. Int J Dermatol. 2006;45:897-908.
5. Wolff K, Johnson RA, Suurmond R. Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology. 5th ed. New York, N.Y.: McGraw-Hill; 2005:556-559.
6. Özkaya E. Drug related clinical pattern in fixed drug eruption. Eur J Dermatol. 2000;10:288-291.
7. Özkaya E. Fixed drug eruption: state of the art. J Dtsch Dermatol Ges. 2008;6:181-188.