Abstract
Drug-induced pigmentation represents 10 to 20% of all cases of acquired hyperpigmentation and this hypothesis must be systematically raised in unexplained pigmented lesions especially in elderly people. The pathogenesis of drug-induced pigmentation is variable according to the causative medication and can involve an accumulation of melanin, sometimes following a nonspecific cutaneous inflammation and often worsened by sun exposure, an accumulation of the triggering drug itself, a synthesis of special pigments under the direct influence of the drug or deposits of iron following damage to the dermal vessels.
The influence of sun exposure is usually obvious in most cases, either by sun-induced melanin synthesis stimulation with formation of complexes between melanin and the causative drug or by transformation of the drug in visible particles usually taken up by dermal macrophages under the influence of sunlight.
The main drugs implicated in causing skin pigmentation are nonsteroidal anti-inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, tetracyclines, heavy metals and psychotropic drugs. Clinical features are very variable according to the triggering molecule, with a large range of patterns and shades which are sometimes more or less reminiscent of the culprit drug. Histological findings are very variable as well but the colored particles are often concentrated within dermal macrophages which are sometimes localized in a distinctive fashion with respect to dermal structures such as vessels or adnexes. Treatment is often limited to sun-avoidance or interruption of treatment with the offending drug but laser therapy recently gave rise to hope of a cure in some cases. These measures are often followed by a fading of the lesions but the pigmentation may last for a long time or may even become permanent in a small percentage of patients.
Similar content being viewed by others
References
Levantine A., Almeyda J. Drug induced changes in pigmentation. Br J Dermatol 1973; 89: 105–112
Granstein R.D., Sober A.J. Drug- and heavy-metal-induced hyperpigmentation. J Am Acad Dermatol 1981; 5: 1–18
Fitzpatrick J.E. New histopathologic findings in drug eruptions. Dermatol Clin 1992; 10: 19–36
Zurcher K., Krebs A. Cutaneous drug reactions. Basel, Karger, 1992
Dubois E.L. Antimalarials in the management of discoid and systemic lupus erythematosus. Semin Arthritis Rheum 1978; 8: 33–51
Koranda F.C. Antimalarials. J Am Acad Dermatol 1981; 4: 650–655
Bailin P.L., Matkaluk R.M. Cutaneous reactions to rheumatological drugs. Clin Rheum Dis 1982; 8: 493–516
Ribrioux A. Synthetic antimalarials and skin. Ann Dermatol Venereol 1990; 117: 975–990
Delage C., Lagace R., Huard J. Pseudocyanotic pigmentation of the skin induced by amiodarone: a light and electron microscopic study. Can Med Assoc J 1975; 112: 1205–1208
Susser W.S., Whitaker-Worth D.L., Grant-Kels J.M. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol 1999; 40; 367–398
Bronner A., Hood A. Cutaneous complications of chemotherapeutic agents. J Am Acad Dermatol 1983; 9: 645–663
Harrison B., Wood C. Cyclophosphamide and pigmentation. BMJ 1972; 1: 352
Pratt C.B., Shanks E.C. Hyperpigmentation of nails from doxorubicin. JAMA 1974; 228: 460
Werner Y., Thornberg B. Cutaneous side effects of bleomycin therapy. Acta Derm Venereol 1976; 56: 155–158
Hrushesky W. Unusual pigmentary changes associated with 5-fluorouracil therapy. Cutis 1980; 26: 181–182
Guillet G., Guillet M., DeMeaux H., et al. Cutaneous pigmented stripes and bleomycin treatment. Arch Dermatol 1986; 122: 381–382
Kumar L., Kochipillai V. Mitoxantrone induced hyperpigmentation. N Z Med J 1990; 103: 55
Llistosella E., Codina A., Alvarez R., et al. Tegafur-induced acral hyperpigmentation. Cutis 1991; 48: 205–207
Perlin E., Ahlgren J. Pigmentary effects from the protracted infusion of 5-fluorouracil. Int J Dermatol 1991; 30: 43–44
Hendrix J., Greer K. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992; 31: 458–466
Konohama A. Blue-gray pigmentation in a patient receiving doxorubicin. J Dermatol 1992; 19: 250–252
Gropper C., Don P., Sadjadi M. Nail and skin hyperpigmentation associated with hydroxyurea therapy for polycythemia vera. Int J Dermatol 1993; 32: 731–733
Yule S., Pearson A., Craft A. Ifosfamide-induced hyperpigmentation. Cancer 1994; 73: 240–241
Allen B., Parker D., Wright A. Reticulate pigmentation due to 5-fluorouracil. Int J Dermatol 1995; 34: 219–220
Baselga E., Drolet B., Casper J., et al. Chemotherapy-associated supravenous hyperpigmentation. Dermatology 1996; 192: 384–385
Kwong Y. Hydroxyurea-induced nail pigmentation. J Am Acad Dermatol 1996; 35: 275–276
Borecky D., Stephenson J., Keeling J., et al. Idarubicin-induced pigmentary changes of the nail. Cutis 1997; 59: 203–204
McGrae J.D., Zelickson A.S. Skin pigmentation secondary to minocycline therapy. Arch Dermatol 1980; 116: 1262–1265
Simons J.J., Morales A. Minocycline and generalized cutaneous pigmentation. J Am Acad Dermatol 1980; 3: 244–247
Patel K., Cheshire D., Vance A. Oral and systemic effects of prolonged minocycline therapy. Br Dent J 1998; 26; 185: 560–562
Eisen D., Hakim M.D. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf 1998; 18: 431–440
Fraunfelder F.T., Randall J.A. Minocycline-induced scleral pigmentation. Ophthalmology 1997; 104: 936–938
Pepine M., Flowers F.P., Ramos-Caro F.A. Extensive cutaneous hyperpigmentation caused by minocycline. J Am Acad Dermatol 1993; 28: 292–295
Noble J.G., Christmas T.J., Chapple C., et al. The black thyroid: an unusual finding during neck exploration. Postgrad Med J 1989; 65: 34–35
Beurey J., Weber M., Jeandel C., et al. Argyria. Therapie 1986; 41: 505–510
Bleehen S.S., Gould D.J., Harrington C.I., et al. Occupational argyria: light and electron microscopic studies and x-ray microanalysis. Br J Dermatol 1981; 104: 19–26
White M.I. Localized argyria caused by silver earrings. Br J Dermatol 1997; 136: 980
Suzuki H., Baba S., Uchigasaki S., et al. Localized argyria with chrysiasis caused by implanted acupuncture needles: distribution and chemical forms of silver and gold in cutaneous tissue by electron microscopy and x-ray microanalysis. J Am Acad Dermatol 1993; 29: 833–837
Legat F.J., Goessler W., Schlagenhaufen C., et al. Argyria after short-contact acupuncture. Lancet 1998; 352: 241
Massi D., Santucci M. Human generalized argyria: a submicroscopic and x-ray spectroscopic study. Ultrastruct Pathol 1998; 22: 47–53
Smith R.W., Leppard B., Barnett N.L., et al. Chrysiasis revisited: a clinical and pathological study. Br J Dermatol 1995; 131: 671–678
Cremer B., Czarnetzki B.M. Skin discolorations under gold jewelry. Dtsch Med Wochenschr 1992; 117: 558
Trotter M.J., Tron V.A., Hollingdale J., et al. Localized chrysiasis induced by laser therapy. Arch Dermatol 1995; 131: 1411–1414
al-Talib R.K., Wright D.H., Theaker J.M. Orange-red birefringence of gold particles in paraffin wax embedded sections: an aid to the diagnosis of chrysiasis. Histopathology 1994; 24: 176–178
Culora G.A., Barnett N., Theaker J.M. Artefacts in electron microscopy: ultrastructural features of chrysiasis. J Pathol 1995; 176: 421–425
Wolf M.E., Richer S., Berk M.A., et al. Cutaneous and ocular changes associated with the use of chlorpromazine. Int J Clin Pharmacol Ther Toxicol 1993; 31: 365–367
Mars U., Larsson B.S. Pheomelanin as a binding site for drugs and chemicals. Pigment Cell Res 1999; 12: 266–274
Carter R.J., Shuster S. Melanocyte-stimulating hormone-mimetic action of the phenothiazines. J Pharm Pharmacol 1978; 30: 233–235
Buckley C., Thomas V., Lewin J., et al. Stelazine-induced pigmentation. Clin Exp Dermatol 1994; 19: 149–151
Bloom D., Krishnan B., Thavundayil J.X., et al. Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics. Acta Psychiatr Scand 1993; 87: 223–224
Lal S., Bloom D., Silver B., et al. Replacement of chlorpromazine with other neuroleptics: effect on abnormal skin pigmentation and ocular changes. J Psychiatry Neurosci 1993; 18: 173–177
O’Croinin F., Zibin T. Re: Replacement of chlorpromazine with other neuroleptics: effect on abnormal skin pigmentation and ocular changes. J Psychiatry Neurosci 1994; 19: 226
Hare P.J. ‘Visage rouge’ from imipramine. Br J Dermatol 1970; 83: 420
Sicari M.C., Lebwohl M., Baral J., et al. Photoinduced dermal pigmentation in patients taking tricyclic antidepressants: histology, electron microscopy, and energy dispersive spectroscopy. J Am Acad Dermatol 1999; 40: 290–293
Narurkar V., Smoller B.R., Hu C.H., et al. Desipramine-induced blue-gray photosensitive pigmentation. Arch Dermatol 1993; 129: 474–476
Atkin D.H., Fitzpatrick R.E. Laser treatment of imipramine-induced hyperpigmentation. J Am Acad Dermatol 2000; 43: 77–80
Karat A.B.A., Jeevaratnam A., Karat S., et al. Controlled clinical trial of clofazimine in untreated lepromatous leprosy. BMJ 1971; iv: 514–516
Holdiness M.R. A review of the Redman syndrome and rifampicin overdosage. Med Toxicol Adverse Drug Exp 1989; 4: 444–451
Greenberg R.G., Berger T.G. Nail and mucocutaneous hyperpigmentation with azidothymidine therapy. J Am Acad Dermatol 1990; 22: 327–330
Gallais V., Lacour J.P., Perrin C., et al. Acral hyperpigmented macules and longitudinal melanonychia in AIDS patients. Br J Dermatol 1992; 126: 387–391
Gallais V., Lacour J.P., Ortonne J.P. Cutaneous pigmentation disorders in human immunodeficiency virus infection. Ann Dermatol Venereol 1992; 119: 471–478
Lascari A.D. Carotemia. Clin Pediatr (Bologna) 1981; 20: 25–29
Hammer C.J., Melasma induced by oral contraceptive drugs. N W Med Seattle 1968; 67: 251–254
Baker H. Adverse cutaneous reactions to oral contraceptives. Br J Dermatol 1969; 81: 946–949
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dereure, O. Drug-Induced Skin Pigmentation. Am J Clin Dermatol 2, 253–262 (2001). https://doi.org/10.2165/00128071-200102040-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00128071-200102040-00006