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

Keywords Minocycline .Tetracycline .Blueskinpigmentation .BlackbonediseaseCase PresentationA 61-year-old man was brought to the emergency department(ED) for shortness of breath, fatigue, frequent falls, and bluishdiscoloration of his skin. The primary care physician trans-ferred the patient due to concern for cyanosis. On presentationto the ED, the patient was oriented but appeared fatigued. Thepatient was afebrile and had the following vital signs: bloodpressure 161/88 mmHg, pulse 71/min, respiratory rate 16/min,and oxygen saturation 100 % on room air by fingertip pulseoximetry. On physical exam, pupils were 4 mm and reactivebilaterally, extraocular movements were intact, and there wasno nystagmus. Anicteric sclerae were notable for blue pigmen-tation (Fig. 1). Heart sounds were regular, without murmurs,rubs, or gallops. Lung sounds were clear to auscultation bilat-erally. Other thanataxia, the neurological exam was unremark-able. The skin had a generalized bluish tinge, especially on thearms,withdarkerpigmentationonthecheeks(Figs. 2,3and4).There was acne on the back and facial rosacea. Bluish discol-oration was also noted under the proximal nail beds (Fig. 5).When questioned about the skin discoloration, the patient andhisfamilymembersdescribedaninsidiousonset.Photographsof the patient from years ago confirmed that this was notcongenital. Medical history included acne, orthostatichypotension, and Parkinson's disease, for which a deep brainstimulator had been surgically implanted. A comprehensivemedication list was not immediately available; however, thepatientdeniedanyrecentmedicationadditionsoradjustments.The patientwasunemployed, denied anyrecent travel, andnoother members of his household were complaining of fatigueor similar blue skin discoloration.What is the Differential Diagnosis of these SkinChanges?When developing a differential diagnosis (see Table 1) forbluish skin discoloration, one must determine if the patienthas cyanosis. A significant toxicologic cause of blue skinappearance from cyanosis is methemoglobinemia. A carefulhistory may help differentiate between acquired versus con-genital methemoglobinemia. Recent exposure to dapsone,benzocaine, lidocaine, nitrates, or aniline dye raises suspi-cion foracquired methemoglobinemia. Sulfhemoglobinemiashould be considered in patients with a positive methemo-globin reading on co-oximetry, but who do not respond tomethylene blue treatment. Oxidizing agents that may causemethemoglobinemia can also produce sulfhemoglobinemiain the presence of sulfur compounds, such as sulfonamidederivatives, hydrogen sulfide, or gastrointestinal sources [1].Causes of noncyanotic skin discoloration are extensive.Metal deposition (e.g., silver, gold, bismuth) causes blueskin pigmentation. Chronic or improper exposure to silvercan result in a silvery blue or gray skin discoloration knownas argyria. Argyria is caused by silver deposition in the skin,specifically within fibroblasts, macrophages, and in the ex-tracellular matrix. These skin changes are often most signif-icant in sun-exposed areas [2]. Similarly, chrysiasis refers to