Minocycline Toxicity: Case Files of the University of Massachusetts Medical Toxicology Fellowship

Abstract

A 61-year-old man was brought to the emergency department (ED) for shortness of breath, fatigue, frequent falls, and bluish discoloration of his skin. The primary care physician transferred the patient due to concern for cyanosis. On presentation to the ED, the patient was oriented but appeared fatigued. The patient was afebrile and had the following vital signs: blood pressure 161/88 mmHg, pulse 71/min, respiratory rate 16/min, and oxygen saturation 100 % on room air by fingertip pulse oximetry. On physical exam, pupils were 4 mm and reactive bilaterally, extraocular movements were intact, and there was no nystagmus. Anicteric sclerae were notable for blue pigmentation (Fig. 1). Heart sounds were regular, without murmurs, rubs, or gallops. Lung sounds were clear to auscultation bilaterally. Other than ataxia, the neurological exam was unremarkable. The skin had a generalized bluish tinge, especially on the arms, with darker pigmentation on the cheeks (Figs. 2, 3 and 4). There was acne on the back and facial rosacea. Bluish discoloration was also noted under the proximal nail beds (Fig. 5). When questioned about the skin discoloration, the patient and his family members described an insidious onset. Photographs of the patient from years ago confirmed that this was not congenital. Medical history included acne, orthostatic hypotension, and Parkinson's disease, for which a deep brain stimulator had been surgically implanted. A comprehensive medication list was not immediately available; however, the patient denied any recent medication additions or adjustments. The patient was unemployed, denied any recent travel, and no other members of his household were complaining of fatigue or similar blue skin discoloration.

Pigmentary and Other Dermatologic Manifestations of Minocycline: a reminder of adverse effects

“…3 Its lipophilic nature not only promotes wide distribution in tissues, allowing crossing of the bloodbrain barrier, 2,3,7,14 but also reduces resistance. 10,15 Three quarters of the medication is protein bound. 3,7 Maximal dose is reached within 2 hours, with a dose-dependent variability and a halflife of 12-18 hours.…”

“…3,7 Maximal dose is reached within 2 hours, with a dose-dependent variability and a halflife of 12-18 hours. 2,3,10,12,15,16 The renal clearance of minocycline is 1.2-2.2 ml/min with 5-12% of the drug excreted in the urine and 20-35% eliminated in feces. 3 Minocycline produces six metabolites with antimicrobial activity furthering its effectiveness.…”

“…2,9 Hyperpigmentation is the most common side effect from the cumulative administration of minocycline 7 and is often blamed on its rapid absorption and longer half-life. 15 The classic pigmentation presentation patterns have been classified into four separate types (Table 1). Type 1 demonstrates a blueblack pigmentation primarily around areas of previous scarring or inflammation.…”

“…Type 1 demonstrates a blueblack pigmentation primarily around areas of previous scarring or inflammation. 7,9,12,15 Under microscopy, perivascular macrophages laden with granules of pigment chelated with iron, hemosiderin, and ferritin are seen. 7,15 The pigmentation does not correspond to either duration or cumulative dose of minocycline.…”

“…7,9,12,15 Under microscopy, perivascular macrophages laden with granules of pigment chelated with iron, hemosiderin, and ferritin are seen. 7,15 The pigmentation does not correspond to either duration or cumulative dose of minocycline. 9,15 Therefore, it may be more rapidly seen but also resolves with discontinuation of the medication.…”