Medical Care

The most important factor in the management of drug-induced dyspigmentation involves the identification and discontinuation of the offending drug. Most mucocutaneous pigmentation is reversible and spontaneously resolves with avoidance of the inciting drug.

In a scenario in which several drugs may be implicated as the cause of dyspigmentation, a decision must be made between the physician and patient to stop all nonessential medications. Decreasing the dose of any essential, life-saving treatment is often sufficient to diminish drug-related dyschromia. Additionally, merely explaining the benign nature of the cutaneous reaction may alleviate patient anxiety and allow time to determine the offending medication.

In addition, exposure to sun or UV light may increase pigmentation, especially after sensitization with a photosensitizing medication. Sunscreen use and vigilant avoidance of the sun are helpful to prevent progression or recurrence of pigmentary changes.

Finally, topical depigmenting agents and laser treatments (eg, Q-switched alexandrite laser, Q-switched ruby laser) have been reported to improve cases of permanent dyspigmentation. The use of these therapies is controversial because they have shown inconsistent results; further evaluation is needed.

Consultations

For patients whose dyspigmentation may be the result of a systemic illness such as Addison disease, consultation with an internist and/or endocrinologist may be indicated.

Prevention

Avoid further use of the inciting medication.

Koranda FC. Antimalarials. J Am Acad Dermatol. 1981 Jun. 4(6):650-5. [QxMD MEDLINE Link].
Bronner AK, Hood AF. Cutaneous complications of chemotherapeutic agents. J Am Acad Dermatol. 1983 Nov. 9(5):645-63. [QxMD MEDLINE Link].
Fernandez-Obregon AC, Hogan KP, Bibro MK. Flagellate pigmentation from intrapleural bleomycin. A light microscopy and electron microscopy study. J Am Acad Dermatol. 1985 Sep. 13(3):464-8. [QxMD MEDLINE Link].
Haas N, Vogt R, Sterry W. [Shiitake dermatitis: flagellate dermatitis after eating mushrooms]. Hautarzt. 2001 Feb. 52(2):132-5. [QxMD MEDLINE Link].
Hrushesky WJ. Unusual pigmentary changes associated with 5-fluorouracil therapy. Cutis. 1980 Aug. 26(2):181-82. [QxMD MEDLINE Link].
Ghosh, S. K., D. Bandyopadhyay, L. Ghoshal, and S. Basu. Letter: Docetaxel-induced supravenous serpentine dermatitis. Dermatology Online Journal. 2011 Nov 15. 17:(11):16.
Geddes ER, Cohen PR. Antineoplastic agent-associated serpentine supravenous hyperpigmentation: superficial venous system hyperpigmentation following intravenous chemotherapy. South Med J. 2010 Mar. 103(3):231-5. [QxMD MEDLINE Link].
Schallier D, Decoster L, de Greve J. Pemetrexed-induced hyperpigmentation of the skin. Anticancer Res. 2011 May. 31(5):1753-5. [QxMD MEDLINE Link].
Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005. 16:1425-33.
Heidary N, Naik H, Burgin S. Chemotherapeutic agents and the skin: An update. J Am Acad Dermatol. 2008 Apr. 58(4):545-70.
Bleehen SS, Gould DJ, Harrington CI, Durrant TE, Slater DN, Underwood JC. Occupational argyria; light and electron microscopic studies and X-ray microanalysis. Br J Dermatol. 1981 Jan. 104(1):19-26. [QxMD MEDLINE Link].
Tanita Y, Kato T, Hanada K, Tagami H. Blue macules of localized argyria caused by implanted acupuncture needles. Electron microscopy and roentgenographic microanalysis of deposited metal. Arch Dermatol. 1985 Dec. 121(12):1550-2. [QxMD MEDLINE Link].
White MI. Localized argyria caused by silver earrings. Br J Dermatol. 1997 Jun. 136(6):980. [QxMD MEDLINE Link].
Cremer B, Czarnetzki BM. [Skin discolorations under gold jewelry]. Dtsch Med Wochenschr. 1992 Apr 3. 117(14):558. [QxMD MEDLINE Link].
Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998 Jun. 18(6):431-40. [QxMD MEDLINE Link].
McGrae JD Jr, Zelickson AS. Skin pigmentation secondary to minocycline therapy. Arch Dermatol. 1980 Nov. 116(11):1262-5. [QxMD MEDLINE Link].
Pepine M, Flowers FP, Ramos-Caro FA. Extensive cutaneous hyperpigmentation caused by minocycline. J Am Acad Dermatol. 1993 Feb. 28(2 Pt 2):292-5. [QxMD MEDLINE Link].
Simons JJ, Morales A. Minocycline and generalized cutaneous pigmentation. J Am Acad Dermatol. 1980 Sep. 3(3):244-7. [QxMD MEDLINE Link].
Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology. 1997 Jun. 104(6):936-8. [QxMD MEDLINE Link].
Green D, Friedman KJ. Treatment of minocycline-induced cutaneous pigmentation with the Q-switched Alexandrite laser and a review of the literature. J Am Acad Dermatol. 2001 Feb. 44(2 Suppl):342-7. [QxMD MEDLINE Link].
Alster TS, Gupta SN. Minocycline-induced hyperpigmentation treated with a 755-nm Q-switched alexandrite laser. Dermatol Surg. 2004 Sep;. 30(9):1201-4.
Greve B, Schonermark MP, Raulin C. Minocycline-induced hyperpigmentation: Treatment with the Q-switched nd:YAG laser. Lasers Surg Med. 1998. 22(4):223-7.
Wilde JL, English JC,3rd, Finley EM. Minocycline-induced hyperpigmentation. treatment with the neodymium:YAG laser. Arch Dermatol. 1997 Nov. 133(11):1344-6.
Wood B, Munro CS, Bilsland D. Treatment of minocycline-induced pigmentation with the neodymium-yag laser. Br J Dermatol. 1998 Sep;139(3):562.
Kounis NG, Frangides C, Papadaki PJ, Zavras GM, Goudevenos J. Dose-dependent appearance and disappearance of amiodarone-induced skin pigmentation. Clin Cardiol. 1996 Jul. 19(7):592-4. [QxMD MEDLINE Link].
Trimble JW, Mendelson DS, Fetter BF, Ingram P, Gallagher JJ, Shelburne JD. Cutaneous pigmentation secondary to amiodarone therapy. Arch Dermatol. 1983 Nov. 119(11):914-8. [QxMD MEDLINE Link].
Ward HA, Russo GG, Shrum J. Cutaneous manifestations of antiretroviral therapy. J Am Acad Dermatol. 2002 Feb. 46(2):284-93. [QxMD MEDLINE Link].
Shirasaka T, Tadokoro T, Yamamoto Y, Fukutake K, Kato Y, Odawara T, et al. Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients. J Infect Chemother. 2011 Oct. 17(5):602-8. [QxMD MEDLINE Link].
Job CK, Yoder L, Jacobson RR, Hastings RC. Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. J Am Acad Dermatol. 1990 Aug. 23(2 Pt 1):236-41. [QxMD MEDLINE Link].
MacMorran WS, Krahn LE. Adverse cutaneous reactions to psychotropic drugs. Psychosomatics. 1997 Sep-Oct. 38(5):413-22. [QxMD MEDLINE Link].
Wolf ME, Richer S, Berk MA, Mosnaim AD. Cutaneous and ocular changes associated with the use of chlorpromazine. Int J Clin Pharmacol Ther Toxicol. 1993 Aug. 31(8):365-7. [QxMD MEDLINE Link].
Bloom D, Krishnan B, Thavundayil JX, Lal S. Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics. Acta Psychiatr Scand. 1993 Mar. 87(3):223-4. [QxMD MEDLINE Link].
Lal S, Bloom D, Silver B, Desjardins B, Krishnan B, Thavundayil J, et al. Replacement of chlorpromazine with other neuroleptics: effect on abnormal skin pigmentation and ocular changes. J Psychiatry Neurosci. 1993 Jul. 18(4):173-7. [QxMD MEDLINE Link].
Ming ME, Bhawan J, Stefanato CM, McCalmont TH, Cohen LM. Imipramine-induced hyperpigmentation: four cases and a review of the literature. J Am Acad Dermatol. 1999 Feb. 40(2 Pt 1):159-66. [QxMD MEDLINE Link].
Narurkar V, Smoller BR, Hu CH, Bauer EA. Desipramine-induced blue-gray photosensitive pigmentation. Arch Dermatol. 1993 Apr. 129(4):474-6. [QxMD MEDLINE Link].
Sicari MC, Lebwohl M, Baral J, Wexler P, Gordon RE, Phelps RG. Photoinduced dermal pigmentation in patients taking tricyclic antidepressants: histology, electron microscopy, and energy dispersive spectroscopy. J Am Acad Dermatol. 1999 Feb. 40(2 Pt 2):290-3. [QxMD MEDLINE Link].
Atkin DH, Fitzpatrick RE. Laser treatment of imipramine-induced hyperpigmentation. J Am Acad Dermatol. 2000 Jul. 43(1 Pt 1):77-80. [QxMD MEDLINE Link].
Garin Shkolnik T, Feuerman H, Didkovsky E, Kaplan I, Bergman R, Pavlovsky L, et al. Blue-gray mucocutaneous discoloration: a new adverse effect of ezogabine. JAMA Dermatol. 2014 Sep 1. 150(9):984-9. [QxMD MEDLINE Link].
Baker H. Adverse cutaneous reaction to oral contraceptives. Br J Dermatol. 1969 Dec. 81(12):946-9. [QxMD MEDLINE Link].
Blomberg M, Zachariae CO, Grønhøj F. Hyperpigmentation of the face following adalimumab treatment. Acta Derm Venereol. 2009. 89(5):546-7. [QxMD MEDLINE Link].
Kramer KE, Lopez A, Stefanato CM, Phillips TJ. Exogenous ochronosis. J Am Acad Dermatol. 2000 May. 42(5 Pt 2):869-71. [QxMD MEDLINE Link].
Chien KH, Lu DW, Chen JT. Extensive facial skin pigmentation after latanoprost treatment. Cutan Ocul Toxicol. 2009. 28(4):185-7. [QxMD MEDLINE Link].
Sharpe ED, Reynolds AC, Skuta GL, Jenkins JN, Stewart WC. The clinical impact and incidence of periocular pigmentation associated with either latanoprost or bimatoprost therapy. Curr Eye Res. 2007 Dec. 32(12):1037-43. [QxMD MEDLINE Link].
Li CC, Malik SM, Blaeser BF, Dehni WJ, Kabani SP, Boyle N, et al. Mucosal Pigmentation Caused by Imatinib: Report of Three Cases. Head Neck Pathol. 2011 Dec 31. [QxMD MEDLINE Link].
Aleem A. Hypopigmentation of the skin due to imatinib mesylate in patients with chronic myeloid leukemia. Hematol Oncol Stem Cell Ther. 2009;2(2):358-61.
Alexandrescu DT, Dasanu CA, Farzanmehr H, Kauffman L. Persistent cutaneous hyperpigmentation after tyrosine kinase inhibition with imatinib for GIST. Dermatol Online J. 2008 Jul 15;14(7):7.:
Hemesath TJ, Price ER, Takemoto C, Badalian T, Fisher DE. MAP kinase links the transcription factor microphthalmia to c-kit signalling in melanocytes. Nature. 1998 Jan 15;391(6664):298-301.
Ghunawat S, Sarkar R, Garg VK. Imatinib induced melasma-like pigmentation: Report of five cases and review of literature. Indian J Dermatol Venereol Leprol. 2016 Jul-Aug. 82 (4):409-412. [QxMD MEDLINE Link].
Lahiry S, Choudhury S, Mukherjee A, Bhunya PK, Bala M. Polymyxin B-Induced Diffuse Cutaneous Hyperpigmentation. J Clin Diagn Res. 2017 Feb. 11 (2):FD01-FD02. [QxMD MEDLINE Link].
Arya V, Grzybowski J, Schwartz RA. Carotenemia. Cutis. 2003 Jun. 71(6):441-2, 448. [QxMD MEDLINE Link].
Friedman SJ, Butler DF, Pittelkow MR. Perilesional linear atrophy and hypopigmentation after intralesional corticosteroid therapy. Report of two cases and review of the literature. J Am Acad Dermatol. 1988 Sep. 19(3):537-41. [QxMD MEDLINE Link].
Vine K, Meulener M, Shieh S, Silverberg NB. Vitiliginous lesions induced by amyl nitrite exposure. Cutis. 2013 Mar. 91(3):129-36. [QxMD MEDLINE Link].
Halder RM, Nandedkar MA, Neal KW. Pigmentary disorders in ethnic skin. Dermatol Clin. 2003 Oct. 21(4):617-28, vii. [QxMD MEDLINE Link].
McKee PH, Calonje E, Granter SR. Cutaneous adverse reactions to drugs and effects of physical agents. Pathology of the Skin with Clinical Correlations. 3rd ed. London, England: Elsevier; 2005. Vol 1: 638-42.
Trout CR, Levine N, Chang MW. Disorders of hyperpigmentation. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. St. Louis, Mo: Mosby; 2003. Vol 2: 975-1006.

Media Gallery

Perioral chloroquine pigmentation.
Bleomycin flagellate pigmentation.
Adriamycin pigmented macule (arrow) on the tongue.
Minocycline pigmentation of the sclera.
Minocycline pigmentation of the forearms.
Minocycline pigmentation of the lower leg.
Minocycline "muddy" pigmentation of the face in photodistribution.
Amiodarone pigmentation.

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Author

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Harry Dao, Jr, MD Assistant Professor, Department of Dermatology, Baylor College of Medicine

Harry Dao, Jr, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Deborah Zimmer Henderson, MPH University of Texas Southwestern Medical School

Deborah Zimmer Henderson, MPH is a member of the following medical societies: Texas Medical Association

Disclosure: Nothing to disclose.