Summary
Pigmentation is a well recognised adverse effect of minocycline therapy. Various body sites, most notably the skin, nails, bones, thyroid, mouth and eyes are affected and the pigmentation may appear at multiple sites. In general, pigmentation results from long term administration of minocycline at cumulative doses greater than 100g, although cutaneous or oral mucosal pigmentation may appear, regardless of dose or duration of therapy. When the skin is involved, the blue-black pigmentation develops most frequently on the shins, ankles and arms. Other patterns of skin involvement include pigmentation that is either generalised and symmetrical, or that develops at sites of inflammation. The bones of the oral cavity are probably the most frequently affected sites of pigmentation affecting greater than 20% of patients taking minocycline for more than 4 years. In contrast, the oral mucous membranes and teeth are infrquently pigmented from minocycline. Ocular, thyroid and visceral pigmentation is also relatively uncommon and usually develops only with high doses and long term minocycline use. Whereas pigmentation of the skin and oral mucosa is generally reversible when the drug is discontinued, the pigmentation is often permanent when other sites are involved. Although minocycline-induced pigmentation is not harmful, the drug should be discontinued when the adverse effect is recognised. All patients receiving minocycline, especially those treated for longer than 1 year, require screening for the development of pigmentation.
Similar content being viewed by others
References
Humbert P, Treffel P. The tetracyclines in dermatology. J Am Acad Dermatol 1991; 25: 691–7
Klein NC, Cunha BA. Tetracyclines. Med Clin North Am 1995; 79: 789–801
O’Dell JR, Haire CE, Palmer W, et al. Treatment of early rheumatoid arthritis with minocycline or placebo: results of a double-blind, placebo-controlled trial. Arthritis Rheum 1997; 40: 842–8
Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet 1988; 15: 355–66
Siller G, Marcus A. Minocycline-induced oral pigmentation. J Am Acad Dermatol 1994; 30: 350–4
Eady EA, Cove JH, Holland KT, et al. Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients. Br J Dermatol 1990; 122: 233–44
Dysler-Aas K, Hansson H, Miorner G, et al. Pigment deposits in eyes and light-exposed skin during long-term methacycline therapy. Acta Derm Venereol 1974; 54: 209–22
Moller H, Rausing A. Methacycline hyerpigmentation: a five-year follow-up. Acta Derm Venereol 1980; 60: 495–501
Wallman IS, Hilton HB. Teeth pigmented by tetracycline. Lancet 1962; I: 112
Hendricks A. Yellow lunulae with flourescence after tetracycline therapy. Arch Dermatol 1980; 116: 438–40
Walter JF, Macknet KD. Pigmentation of osteoma cutis caused by tetracycline. Arch Dermatol 1979; 115: 1087–8
Hendrix J, Greer K. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992; 3: 458–66
Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol 1996; 134: 693–5
Fenske N, Millns J, Greer K. Minocycline-induced pigmentation at sites of cutaneous inflammation. JAMA 1980; 244: 1103–6
Fleming C, Hunt M, Salisbury ELC, et al. Minocycline-induced hyperpigmentation in leprosy. Br J Dermatol 1996; 134: 784–7
Leffell DJ. Minocycline hydrochloride hyperpigmentation complicating treatment of venous ectasia of the extremities. J Am Acad Dermatol 1991; 24: 501–2
Moritz D, Elewski B. Pigmented postacne osteoma cutis in a patient treated with minocycline: report and review of the literature. J Am Acad Dermatol 1991; 24: 851–3
Sabroe R, Archer C, Harlow D. Minocycline-induced discolouration of the sclerae. Br J Dermatol 1996; 135: 314–6
Argenyi Z, Finelli L. Minocycline-related cutaneous hyperpigmentation as demonstrated by light microscopy, electron microscopy and x-ray energy spectroscopy. J Cutan Pathol 1987; 14: 176–80
Okada N, Sato S, Sasou T. Characterization of pigmented granules in minocycline-induced cutaneous pigmentation: observations using flourescent microscopy and high-performance chromatography. Br J Dermatol 1993; 129: 403–7
Gordon C, Sparano B, Iatropoulos M. Hyperpigmentation of skin associated with minocycline therapy. Arch Dermatol 1985; 121: 618–23
Simons J, Morales A. Minocycline and general cutaneous pigmentation. J Am Acad Dermatol 1980; 3: 244–7
Chu P, Van S. Minocycline hyperpigmentation localized to the lips: an unusual fixed drug reaction? J Am Acad Dermatol 1994; 30(5): 802–3
Ridgway H, Reizner GT. Acquired pseudo-mongolian spot associated with minocycline therapy. Arch Dermatol 1992; 128: 565–6
Dwyer CM, Cuddihy AM. Skin pigmentation due to minocycline treatment of facial dermatoses. Br J Dermatol 1993; 129: 158–62
Layton A, Cunliffe W. Minocycline-induced pigmentation in the treatment of acne: a review and personal observations. J Dermatol Treatment 1989; 1: 9–12
Hutchinson S, Burrows DJ. Minocycline-induced pigmentation. Br J Dermatol 1992; 127: 47–8
Layton AM, Cunliffe WJ. Minocycline induced pigmentation in the treatment of acne — a review and personal observations. J Dermatol Treat 1989; 1: 9–12
Eedy D, Burrows P. Minocycline-induced pigmentation occurring in two sisters. Clin Exp Derm 1991; 16: 55–7
Collins P, Cotterill J. Minocycline-induced pigmentation resolves after treatment with the Q-switched ruby laser. Br J Dermatol 1996; 136: 317–9
Liu TT, May N. Pigmentary changes due to long term minocycline therapy. Cutis 1985; 35: 254–5
Daniel C, Scher R. Nail changes caused by systemic drugs or ingestants. Dermatol Clin 1985; 3: 491–500
Kestel J. Photo-onycholysis from minocycline: side-effects of minocycline therapy. Cutis 1981; 28: 53–4
Mallon E, Dawber R. Longitudinal melanonychia induced by minocycline. Br J Dermatol 1994; 130: 794–801
Poliak SC, DiGiovanna JJ, Gross EG. Minocycline-associated tooth discoloration in young adults. JAMA 1985; 254: 2930–2
Berger R, Mandel E, Hayes T. Minocycline staining of the oral cavity. J Am Acad Dermatol 1989; 21: 1300–1
Rosen T, Hoffmann T. Minocycline-induced discoloration of the permanent teeth. J Am Acad Dermatol 1989; 21: 569
Salman R, Salman D, Glickman R. Minocycline-induced pigmentation of the oral cavity. J Oral Med 1985; 40: 154–7
Westbury LE, Najera A. Minocycline-induced intraoral pharmacogenic pigmentation: case reports and review of the literature. J Periodontol 1997; 68: 84–91
Ciancio S, Mather M, McMullen J. An evaluation of minocycline in patients with periodontal disease. J Periodontol 1982; 51: 530–4
Siller GM, Tod MA, Savage NW. Minocycline-induced oral pigmentation. J Am Acad Dermatol 1994; 30: 350–4
Cohen BD, Abrams BL. An unusual case of stained roots of unerupted third molars. Gen Dent 1989; 37: 342–3
Meyerson M, Cohen P, Hymes S. Lingual hyperpigmentation associated with minocycline therapy. Oral Surg Oral Med Oral Pathol 1995; 79: 180–4
Dummett C, Barens G. Pigmentation of the oral tissues: a review of the literature. J Periodontol 1967; 38: 360–78
Eisen D. Minocycline-induced oral hyperpigmentation. Lancet 1997; 349(9049): 400
Odell E, Hodgson R, Haskell R. Oral presentation of minocycline-induced black bone disease. Oral Surg Oral Med Oral Pathol 1995; 79: 459–61
Kelly R, Kanegis L. Metabolism and tissue distribution of radioisotopically labelled minocycline. Toxicol Appl Pharmacol 1967; 11: 171–83
Atwood HD, Dennett X. A black thyroid and minocycline treatment. BMJ 1976; 2: 1109–10
Landes S, Schelper R, Fermin T, et al. Black thyroid syndrome: exaggeration of a normal process? Am J Clin Pathol 1986; 85: 411–8
Folson D, Gauderer M, Dahms W. Nodular hyperplasia, black thyroid and chronic minocycline ingestion in a teenager. Arch Surg 1992; 127: 1476–7
Benitz KF, Roberts G, Vusa A. Morphologic effects of minocycline in lab animals. Toxicol Appl Pharm 1967; 11: 150–70
Enochs W, Nilges M, Swartz H. The minocycline-induced thyroid pigmentation and several synthetic models: identification and characterization by electron paramagnetic resonance spectroscopy. J Pharm Exp Ther 1993: 266: 1164–76
Taurog A, Dorris M, Doerge D. Minocycline and the thyroid: anti-thyroid effects of the drug and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland. Thyroid 1996; 6(3): 211–9
Alexander CB, Herrara GA, Jaffe K, et al. Black thyroid: clinical manifestations, ultrastructural findings, and possible mechanisms. Hum Pathol 1985; 16: 72–8
Butler J, Marks R, Sutherland R. Cutaneous and cardiac valvular pigmentation with minocycline. Clin Exp Dermatol 1985; 10: 432–7
Hunt M, Salisbury E, Grace J, et al. Black breast milk due to minocycline therapy. Br J Dermatol 1996; 134: 943–4
Basler RSW, Lynch PJ. Black galactorrhea as a consequence of minocycline and phenothiazine therapy. Arch Dermatol 1988; 121: 417–8
Rumback M, Pitcock JA, Palmieri GMA, et al. Black bones following long-term minocycline treatment. Arch Pathol Lab Med 1991; 115: 939–41
Wolfe I, Reichmister J. Minocycline hyperpigmentation: skin, tooth, nail and bone involvement. Cutis 1984; 33: 457–8
Basler R. Minocycline-related hyperpigmentation. Arch Dermatol 1985; 121: 606–8
Okland S, Prolo DJ. The significance of yellow bone. JAMA 1981; 246: 761–3
Angeloni V, Salasche S, Ortiz R. Nail, skin, and scleral pigmentation induced by minocycline. Cutis 1987; 40: 229–33
Messmer E, Font R, Sheldon G, et al. Pigmented conjunctival cysts following tetracycline/minocycline therapy. Ophthalmology 1983; 90: 1462–8
Morrow GL, Abbott RL. Minocycline-induced scleral, dental, and dermal pigmentation. Am J Ophthalmol 1998; 125: 396–7
Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology 1997; 104: 936–8
Brothers D, Hidayat A. Conjunctival pigmentation associated with tetracycline medication. Ophthalmology 1981; 88: 1212–5
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Eisen, D., Hakim, M.D. Minocycline-Induced Pigmentation. Drug-Safety 18, 431–440 (1998). https://doi.org/10.2165/00002018-199818060-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199818060-00004