Out of the Blue: A Case of Blue Subungual Discoloration Associated with Prolonged Tetracycline Use

Abstract

Tetracycline derivatives are antibiotics such as minocycline and doxycycline that have been commonly utilized for inflammatory dermatological conditions such as acne and rosacea. Hyperpigmentation of the skin, nails, thyroid, oral mucosa, teeth, and bones is a known but rare side effect of prolonged tetracycline use. The hyperpigmentation typically takes months to years to develop. There may also be residual changes to the skin after discontinuation of the medication. For this reason, the time tetracyclines are used should be minimized and patients should be monitored for the skin findings. Subungual discoloration carries a broad differential including infectious, inflammatory, metabolic, malignant or systemic diseases. Knowledge of this side effect is crucial in order to avoid unnecessary testing in determining the etiology of the subungual discoloration. We report on a case of a patient who has been on long-term minocycline use for adult acne management. He was initially on minocycline for six years, but due to minocycline-induced hyperpigmentation of his ears and fingernails, he had switched to doxycycline. One year later, the skin hyperpigmentation of the ears regressed; however, the blue subungual hyperpigmentation of his hands progressively become more prominent without any other significant symptoms.

Doxycycline-Associated Hyperpigmentation: A Case Report and Literature Review

“…This ranged from two days to 12 years; the median time for onset of hyperpigmentation was eight months. Including our patient, the hyperpigmentation appeared within one or fewer months after starting doxycycline in seven patients (38.9%) and within 12 or fewer months in 13 patients (72.2%) [ 7 - 10 , 13 - 15 ]. Doxycycline-associated hyperpigmentation occurred in 14 months in one patient, 36 months in one patient, and 37 months in another patient [ 12 , 14 ].…”

“…Six of the patients, including the patient in this report, were taking a daily dose of 200 mg, as either a single 200 mg dose (three people) or a 100 mg dose twice each day (three people) [ 8 , 12 , 14 , 16 ]. Four patients were receiving 100 mg as a single daily dose [ 9 , 10 , 15 ]. The remaining patients were receiving 200-300 mg daily (three patients), 100 mg three times daily (one patient), 100-200 mg daily (one patient), or 100 mg once or twice daily (one patient) [ 7 , 10 , 14 ].…”

“…Hydroxychloroquine was the most common concurrently used medication, being used in five patients [ 10 , 14 ]. Two patients previously used another tetracycline agent before starting doxycycline [ 9 , 15 ].…”

Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: A case report

“…5,6 Minocycline, a structurally similar tetracycline to doxycycline, is also reported to cause blue-grey discoloration (type I MIP). 6 However, type I MIP is thought to occur through local pigment deposits by macrophages, a different mechanism than seen in doxycycline-induced pigmentation. 6…”

“…5 However, minocycline is known to cause stage I minocycline-induced pigmentation (MIP), which can appear blue-grey in colour, often affecting and scars. 6 Here, we present a patient who developed blue-grey hyperpigmentation after being administered vandetanib, which darkened after being administered oral doxycycline.…”