Minocycline-induced hyperpigmentation

Journal of Family Practice, August, 1995 by Ping-Hsin Hung, James B. Caldwell, William D. James

Although tetracycline, if given after 8 years of age, has not been reported to cause discoloration of the permanent teeth, minocycline can cause a gray discoloration that usually does not resolve. In a retrospective survey, minocycline-induced tooth discoloration was noted in 4 of 72 (5.6%) patients.(23) A later study that examined 100 patients found only 2 with discoloration of the teeth.(24) This pigment is usually located on the incisal one half to three fourths of the crown, sparing the gingival aspect, with a characteristic darker band of discoloration in the middle of the tooth.(23)(25) This differs from tetracycline, which generally produces staining of the gingival one third of the tooth.(25)

The mechanism of the discoloration is unclear. Adult teeth are minimally active metabolically. Dentinogenesis continues throughout life at a greatly reduced rate after eruption; however, minocycline deposition in the dentine is unlikely to affect the color of an adult tooth.(26) Tetracyclines have been known to demineralize enamel in vitro. Minocycline may etch the tooth surface through long-term contact by attaching to glycoproteins in the acquired pellicle. It then may become oxidized on exposure to oxygen or bacterial activity.(26) Minocycline is also found in gingival fluid at a concentration five times that of serum and may intrinsically stain the enamel by diffusing through the pulp.(24) Minocycline's strong affinity for iron and its ability to form insoluble salts also may play a role.(23)(25)

In similiar cases, excessive pigmentation caused by minocycline has been attributed to ecchymoses, uneven tans, or poorly applied make-up. The etiology in this particular patient was discovered through a careful history. However, the differential diagnosis included hemochromatosis, ochronosis, and hyperpigmentation induced by a drug or heavy metal. Most patients in whom hemochromatosis is diagnosed are between the ages of 40 and 60. Ninety percent of these patients have excessive pigmentation, most often seen on the face, neck, extensor forearms, hands, genitalia, lower legs, and in scars. Ochronosis results from a deficiency of homogentisic acid oxidase and leads to deposition of homogentisic acid in tissues. Its earliest manifestations are pigmentation of the sclerae and ears that is usually seen in patients between the ages of 20 and 40. Phenothiazines,(10) antimalarials,(11) imipramine hydrochloride,(21) amiodarone hydrochloride, and heavy metals, such as silver, also should be considered in the differential diagnosis of acquired, widespread hyperpigmentation.

Pigmentation associated with minocycline most often appears in patients after long-term therapy, usually at doses greater than 100 mg per day. However, there has been a report of pigmentation after taking minocycline for only 3 weeks, indicating that this phenomenon is not always dose-related.(5) The extent of hyperpigmentation also does not appear to correlate with the amount of drug taken. In most cases, resolution of the cutaneous pigment occurs after cessation of the drug, with the time to resolution proportional to the severity of the pigmentation. Discoloration of the teeth, however, is generally permanent.