AMIODARONE More than 75% of patients with greater than 40-g cumulative dose after >4 months of therapy. More common in skin phototypes I and II, and may be limited to the light-exposed areas in a small proportion (8%) of patients. Dusky-red erythema and later, blue-gray dermal melanosis (Fig. 23-9) in exposed areas (the face and hands). Lipofuscin-type pigment deposited in macrophages and endothelial cells.

ANTIMALARIALSChloroquine, hydroxychloroquine. Occurs in 25% of individuals who take the drug for >4 months. Brownish, gray-brown, and/or blue-black discoloration resulting from melanin or hemosiderin. Over shins; the face and nape of neck; hard palate; under finger- and toenails (see Section 32); may also occur in the cornea and retina. Quinacrine: Yellow, yellow-green skin, and sclerae (resembling icterus); yellow-green fluorescence of the nail bed with Wood lamp.

MINOCYCLINE Onset delayed, usually after total dose of >50 g, but may occur after a small dose. Type I is noted in areas of scarring or inflammation, often the face (iron chelates of minocycline). Type II is seen in previously normal skin (lower extremities) and is caused by pigmented metabolites. Type III develops in sun exposed areas and is related to melanin deposition in macrophages. Type IV has been described in the back of patients with scarring and stains for calcium and melanin. Blue-gray or slate-gray pigmentation (Fig. 23-10). Distributed on extensor legs, ankles, dorsa of the feet, the face, especially around eyes; sites of trauma or inflammation such as acne scars, contusions, abrasions; hard palate, teeth; nails.

CLOFAZIMINE Orange, reddish brown (range, pink to black) discoloration, ill-defined on light-exposed areas; conjunctivae; accompanied by red sweat, urine, feces. Subcutaneous fat is orange.

ZIDOVUDINE Brown macules on lips or oral mucosa; longitudinal brown bands in nails.

PHENYTOIN High dose over a long period of time (>1 year). Discoloration is spotty, resembling melasma, in light-exposed areas and is caused by melanin.

BLEOMYCIN Tan to brown to black and results from an increase in epidermal melanin at sites of minor inflammation, that is, parallel linear streaks at sites of excoriations caused by scratching ("flagellate" pigmentation), most commonly on the back, elbows, small joints, and nails.

CYCLOPHOSPHAMIDE Brown. Diffuse or discrete macules on elbows; palms with Addisonian-like pigmentation (see Fig. 15-8) and macules.

ACTH Addisonian pigmentation of skin and oral mucosa. First 13 amino acids of ACTH are identical to α-melanocyte-stimulating hormone (MSH) (see Fig. 15-8).

ESTROGENS/PROGESTERONE Caused by endogenous and exogenous estrogen combined with progesterone, that is, during pregnancy or with oral contraceptive therapy. Sunlight causes marked darkening of pigmentation. Tan/brown. Melasma (see Fig. 13-9).

SILVER (ARGYRIA OR ARGYROSIS)Source: Silver nitrate nose drops; silver sulfadiazine applied as an ointment. Silver sulfide (photographic film). Blue-gray discoloration. Primarily areas exposed to light, that is, the face, dorsa of the hands, nails, and conjunctiva; also diffuse.

IRONSource: IM iron injections; multiple blood transfusions. Brown or blue-gray discoloration. Generalized; also local deposits at site of injection.

CAROTENE Ingestion of large quantities of β-carotene-containing vegetables; β-carotene tablets. Yellow-orange discoloration. Most apparent on the palms and soles.