Characterization of pigmented granules in minocycline-induced cutaneous pigmentation: observations using fluorescence microscopy and high-performance liquid chromatography

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Abstract
We describe a technique to facilitate histopathological detection and quantitative measurement of trace amounts of tissue minocycline. In a patient with minocycline‐induced hyperpigmentation, a series of biopsies were taken from the affected skin over a period of 54 months, and examined for tissue minocyclinc deposition. Frozen sections treated with 1 m MgCl2‐ethanol yielded minocycline‐specific yellowish fluorescence, the location of which corresponded to clumps of granular deposits in the dermis. A decrease in the number of fluorescent granules correlated with the clinical resolution of hyperpigmentation and a significant decrease in the tissue minocycline level. Our data also provide further support for the concept that the pigment granules contain insoluble complexes of minocycline chelated with iron. The fluorescence technique is simple, sensitive, and reproducible.