Cutaneous ultrastructural changes and photosensitivity associated with amiodarone therapy.

Amiodarone, an antiarrhythmic agent, is known to cause photosensitivity and cutaneous hyperpigmentation. Five patients taking this drug for periods of 1 to 48 months were studied. Skin biopsy specimens taken from a sun-exposed site were assessed by light microscopy, electron microscopy, and direct immunofluorescence. Three patients allowed comparative studies to be done on a biopsy specimen from non-sun-exposed skin. Light microscopy findings, including special stains, were not diagnostic of amiodarone-associated cutaneous changes. Electron microscopy, however, displayed distinctive intracytoplasmic inclusions in many cell types, some of which have not been reported previously. These inclusions represent phospholipid membranes associated with amiodarone or its metabolites as the result of a drug-induced lipidosis. Previous reports had postulated the inclusions were lipofuscin. Sun exposure may accelerate the formation of these intracellular deposits because they are more prominent in sun-exposed skin. Four of the above five cases, plus two additional patients, had symptoms compatible with a photosensitivity. Porphyrin assays were normal. Of the six patients phototested, three showed acute reactions to ultraviolet A (UVA) and ultraviolet B (UVB) and significant delayed reactions to UVA and/or UVB. The patients who had normal phototesting were on the drug for shorter periods than those with positive tests.