Photoinduced dermal pigmentation in patients taking tricyclic antidepressants: histology, electron microscopy, and...

Two patients had been taking long-term tricyclic antidepressant therapy. Each developed a blue to slate-gray hyperpigmentation in sun-exposed areas. On histologic examination there were refractile golden brown granules free in the dermis along collagen bundles. Similar pigment was present in macrophages and along the basement membrane zone. The granules stained for melanin, but not for iron, and were bleached by the permanganate method. Electron microscopy showed varying size and shaped electron-dense granules within lysosomes and free in the dermis, which, in unstained sections, showed a less dense peripheral halo. This peripheral halo was also evident on light microscopy. Energy dispersive spectroscopy showed these granules to be rich in copper and sulfur (elements present in tyrosinase and pheomelanin, respectively). We believe that this represents a drug-melanosome complex, which is most likely caused by chronic photoactivation.