Imipramine hyperpigmentation: a slate-gray discoloration caused by long-term imipramine administration

A 48-year-old white woman, skin type III, had a slate-gray discoloration of the face and dorsa of both hands after ingesting imipramine, 150 mg/day for 5 years. Her iris color was also darkened. One year after cessation of the therapy, the discoloration became lighter. Sun-protected skin showed no discoloration. Light microscopy revealed an accumulation of doubly refractile golden yellow granules in the papillary dermis, mostly scattered, with some concentration around the blood vessels but not in the endothelial cells. Electron micrographs showed numerous amorphous electron-dense inclusion bodies in histiocytes, phagocytes, fibroblasts, and dermal dendrocytes. Melanosomes were phagocytosed in the same cells but in separated locations. Imipramine is structurally related to chlorpromazine and can cause slate-gray discoloration. However, the color of the granules deposited in the papillary dermis is golden-yellow and they are not deposited in endothelial cells.