Excess melanin and the presence of hemosiderin around sweat glands produce diffuse pigmentation in patients with hemochromatosis. Some of the drugs that cause hyperpigmentation include antimalarials, tetracyclines, hormones, cancer chemotherapeutic agents, phenothiazines, and nitrogen compounds such as mechlorethamine hydrochloride. Heavy metals such as silver, gold, and bismuth produce a slate-blue pigmentation. Chronic arsenic poisoning may produce droplike hypomelanotic macules on a background of diffuse bronze hyperpigmentation. Phenothiazine drugs, such as chlorpromazine, can induce brown-staining granular deposits of unknown composition within the dermis as well as increased melanization within the epidermis.
Some drugs cause hyperpigmentation predominantly in exposed skin areas.
Amiodarone, an antiarrhythmic and antianginal drug, may cause photosensitivity and blue-gray pigmentation in such areas. In two male patients who received chronic amiodarone therapy, this agent and its major metabolite, desethylamiodarone, were present in the dermis at concentrations 10 times higher in sun-exposed sites than in covered sites. Histologic examination revealed macrophages that contained lipofuscin-like pigment in their lysosomes. The prolonged photosensitivity, which lasted up to four months after amiodarone was discontinued, may have resulted from persistence of the drug in the skin. The use of sunscreens that protect in the UVA range may diminish the photosensitivity associated with amiodarone.