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Drug Safety

, Volume 18, Issue 6, pp 431–440 | Cite as

Minocycline-Induced Pigmentation

Incidence, Prevention and Management
  • Drore Eisen
  • Miriam D. Hakim
Review Article Pharmacoepidemiology

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.

Keywords

Adis International Limited Acne Oral Cavity Dermatol Minocycline 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Humbert P, Treffel P. The tetracyclines in dermatology. J Am Acad Dermatol 1991; 25: 691–7PubMedCrossRefGoogle Scholar
  2. 2.
    Klein NC, Cunha BA. Tetracyclines. Med Clin North Am 1995; 79: 789–801PubMedGoogle Scholar
  3. 3.
    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: 842–8PubMedCrossRefGoogle Scholar
  4. 4.
    Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet 1988; 15: 355–66PubMedCrossRefGoogle Scholar
  5. 5.
    Siller G, Marcus A. Minocycline-induced oral pigmentation. J Am Acad Dermatol 1994; 30: 350–4PubMedCrossRefGoogle Scholar
  6. 6.
    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: 233–44PubMedCrossRefGoogle Scholar
  7. 7.
    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: 209–22Google Scholar
  8. 8.
    Moller H, Rausing A. Methacycline hyerpigmentation: a five-year follow-up. Acta Derm Venereol 1980; 60: 495–501PubMedGoogle Scholar
  9. 9.
    Wallman IS, Hilton HB. Teeth pigmented by tetracycline. Lancet 1962; I: 112Google Scholar
  10. 10.
    Hendricks A. Yellow lunulae with flourescence after tetracycline therapy. Arch Dermatol 1980; 116: 438–40PubMedCrossRefGoogle Scholar
  11. 11.
    Walter JF, Macknet KD. Pigmentation of osteoma cutis caused by tetracycline. Arch Dermatol 1979; 115: 1087–8PubMedCrossRefGoogle Scholar
  12. 12.
    Hendrix J, Greer K. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992; 3: 458–66CrossRefGoogle Scholar
  13. 13.
    Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol 1996; 134: 693–5PubMedCrossRefGoogle Scholar
  14. 14.
    Fenske N, Millns J, Greer K. Minocycline-induced pigmentation at sites of cutaneous inflammation. JAMA 1980; 244: 1103–6PubMedCrossRefGoogle Scholar
  15. 15.
    Fleming C, Hunt M, Salisbury ELC, et al. Minocycline-induced hyperpigmentation in leprosy. Br J Dermatol 1996; 134: 784–7PubMedCrossRefGoogle Scholar
  16. 16.
    Leffell DJ. Minocycline hydrochloride hyperpigmentation complicating treatment of venous ectasia of the extremities. J Am Acad Dermatol 1991; 24: 501–2PubMedCrossRefGoogle Scholar
  17. 17.
    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: 851–3PubMedCrossRefGoogle Scholar
  18. 18.
    Sabroe R, Archer C, Harlow D. Minocycline-induced discolouration of the sclerae. Br J Dermatol 1996; 135: 314–6PubMedCrossRefGoogle Scholar
  19. 19.
    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: 176–80PubMedCrossRefGoogle Scholar
  20. 20.
    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: 403–7PubMedCrossRefGoogle Scholar
  21. 21.
    Gordon C, Sparano B, Iatropoulos M. Hyperpigmentation of skin associated with minocycline therapy. Arch Dermatol 1985; 121: 618–23PubMedCrossRefGoogle Scholar
  22. 22.
    Simons J, Morales A. Minocycline and general cutaneous pigmentation. J Am Acad Dermatol 1980; 3: 244–7PubMedCrossRefGoogle Scholar
  23. 23.
    Chu P, Van S. Minocycline hyperpigmentation localized to the lips: an unusual fixed drug reaction? J Am Acad Dermatol 1994; 30(5): 802–3PubMedCrossRefGoogle Scholar
  24. 24.
    Ridgway H, Reizner GT. Acquired pseudo-mongolian spot associated with minocycline therapy. Arch Dermatol 1992; 128: 565–6PubMedCrossRefGoogle Scholar
  25. 25.
    Dwyer CM, Cuddihy AM. Skin pigmentation due to minocycline treatment of facial dermatoses. Br J Dermatol 1993; 129: 158–62PubMedCrossRefGoogle Scholar
  26. 26.
    Layton A, Cunliffe W. Minocycline-induced pigmentation in the treatment of acne: a review and personal observations. J Dermatol Treatment 1989; 1: 9–12CrossRefGoogle Scholar
  27. 27.
    Hutchinson S, Burrows DJ. Minocycline-induced pigmentation. Br J Dermatol 1992; 127: 47–8CrossRefGoogle Scholar
  28. 28.
    Layton AM, Cunliffe WJ. Minocycline induced pigmentation in the treatment of acne — a review and personal observations. J Dermatol Treat 1989; 1: 9–12CrossRefGoogle Scholar
  29. 29.
    Eedy D, Burrows P. Minocycline-induced pigmentation occurring in two sisters. Clin Exp Derm 1991; 16: 55–7PubMedCrossRefGoogle Scholar
  30. 30.
    Collins P, Cotterill J. Minocycline-induced pigmentation resolves after treatment with the Q-switched ruby laser. Br J Dermatol 1996; 136: 317–9CrossRefGoogle Scholar
  31. 31.
    Liu TT, May N. Pigmentary changes due to long term minocycline therapy. Cutis 1985; 35: 254–5PubMedGoogle Scholar
  32. 32.
    Daniel C, Scher R. Nail changes caused by systemic drugs or ingestants. Dermatol Clin 1985; 3: 491–500PubMedGoogle Scholar
  33. 33.
    Kestel J. Photo-onycholysis from minocycline: side-effects of minocycline therapy. Cutis 1981; 28: 53–4PubMedGoogle Scholar
  34. 34.
    Mallon E, Dawber R. Longitudinal melanonychia induced by minocycline. Br J Dermatol 1994; 130: 794–801PubMedCrossRefGoogle Scholar
  35. 35.
    Poliak SC, DiGiovanna JJ, Gross EG. Minocycline-associated tooth discoloration in young adults. JAMA 1985; 254: 2930–2PubMedCrossRefGoogle Scholar
  36. 36.
    Berger R, Mandel E, Hayes T. Minocycline staining of the oral cavity. J Am Acad Dermatol 1989; 21: 1300–1PubMedCrossRefGoogle Scholar
  37. 37.
    Rosen T, Hoffmann T. Minocycline-induced discoloration of the permanent teeth. J Am Acad Dermatol 1989; 21: 569PubMedCrossRefGoogle Scholar
  38. 38.
    Salman R, Salman D, Glickman R. Minocycline-induced pigmentation of the oral cavity. J Oral Med 1985; 40: 154–7PubMedGoogle Scholar
  39. 39.
    Westbury LE, Najera A. Minocycline-induced intraoral pharmacogenic pigmentation: case reports and review of the literature. J Periodontol 1997; 68: 84–91PubMedCrossRefGoogle Scholar
  40. 40.
    Ciancio S, Mather M, McMullen J. An evaluation of minocycline in patients with periodontal disease. J Periodontol 1982; 51: 530–4CrossRefGoogle Scholar
  41. 41.
    Siller GM, Tod MA, Savage NW. Minocycline-induced oral pigmentation. J Am Acad Dermatol 1994; 30: 350–4PubMedCrossRefGoogle Scholar
  42. 42.
    Cohen BD, Abrams BL. An unusual case of stained roots of unerupted third molars. Gen Dent 1989; 37: 342–3PubMedGoogle Scholar
  43. 43.
    Meyerson M, Cohen P, Hymes S. Lingual hyperpigmentation associated with minocycline therapy. Oral Surg Oral Med Oral Pathol 1995; 79: 180–4Google Scholar
  44. 44.
    Dummett C, Barens G. Pigmentation of the oral tissues: a review of the literature. J Periodontol 1967; 38: 360–78Google Scholar
  45. 45.
    Eisen D. Minocycline-induced oral hyperpigmentation. Lancet 1997; 349(9049): 400PubMedCrossRefGoogle Scholar
  46. 46.
    Odell E, Hodgson R, Haskell R. Oral presentation of minocycline-induced black bone disease. Oral Surg Oral Med Oral Pathol 1995; 79: 459–61Google Scholar
  47. 47.
    Kelly R, Kanegis L. Metabolism and tissue distribution of radioisotopically labelled minocycline. Toxicol Appl Pharmacol 1967; 11: 171–83PubMedCrossRefGoogle Scholar
  48. 48.
    Atwood HD, Dennett X. A black thyroid and minocycline treatment. BMJ 1976; 2: 1109–10CrossRefGoogle Scholar
  49. 49.
    Landes S, Schelper R, Fermin T, et al. Black thyroid syndrome: exaggeration of a normal process? Am J Clin Pathol 1986; 85: 411–8Google Scholar
  50. 50.
    Folson D, Gauderer M, Dahms W. Nodular hyperplasia, black thyroid and chronic minocycline ingestion in a teenager. Arch Surg 1992; 127: 1476–7CrossRefGoogle Scholar
  51. 51.
    Benitz KF, Roberts G, Vusa A. Morphologic effects of minocycline in lab animals. Toxicol Appl Pharm 1967; 11: 150–70CrossRefGoogle Scholar
  52. 52.
    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: 1164–76Google Scholar
  53. 53.
    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): 211–9PubMedGoogle Scholar
  54. 54.
    Alexander CB, Herrara GA, Jaffe K, et al. Black thyroid: clinical manifestations, ultrastructural findings, and possible mechanisms. Hum Pathol 1985; 16: 72–8PubMedCrossRefGoogle Scholar
  55. 55.
    Butler J, Marks R, Sutherland R. Cutaneous and cardiac valvular pigmentation with minocycline. Clin Exp Dermatol 1985; 10: 432–7PubMedCrossRefGoogle Scholar
  56. 56.
    Hunt M, Salisbury E, Grace J, et al. Black breast milk due to minocycline therapy. Br J Dermatol 1996; 134: 943–4PubMedCrossRefGoogle Scholar
  57. 57.
    Basler RSW, Lynch PJ. Black galactorrhea as a consequence of minocycline and phenothiazine therapy. Arch Dermatol 1988; 121: 417–8CrossRefGoogle Scholar
  58. 58.
    Rumback M, Pitcock JA, Palmieri GMA, et al. Black bones following long-term minocycline treatment. Arch Pathol Lab Med 1991; 115: 939–41Google Scholar
  59. 59.
    Wolfe I, Reichmister J. Minocycline hyperpigmentation: skin, tooth, nail and bone involvement. Cutis 1984; 33: 457–8PubMedGoogle Scholar
  60. 60.
    Basler R. Minocycline-related hyperpigmentation. Arch Dermatol 1985; 121: 606–8PubMedCrossRefGoogle Scholar
  61. 61.
    Okland S, Prolo DJ. The significance of yellow bone. JAMA 1981; 246: 761–3CrossRefGoogle Scholar
  62. 62.
    Angeloni V, Salasche S, Ortiz R. Nail, skin, and scleral pigmentation induced by minocycline. Cutis 1987; 40: 229–33PubMedGoogle Scholar
  63. 63.
    Messmer E, Font R, Sheldon G, et al. Pigmented conjunctival cysts following tetracycline/minocycline therapy. Ophthalmology 1983; 90: 1462–8PubMedGoogle Scholar
  64. 64.
    Morrow GL, Abbott RL. Minocycline-induced scleral, dental, and dermal pigmentation. Am J Ophthalmol 1998; 125: 396–7PubMedCrossRefGoogle Scholar
  65. 65.
    Fraunfelder FT, Randall JA. Minocycline-induced scleral pigmentation. Ophthalmology 1997; 104: 936–8PubMedGoogle Scholar
  66. 66.
    Brothers D, Hidayat A. Conjunctival pigmentation associated with tetracycline medication. Ophthalmology 1981; 88: 1212–5PubMedGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Drore Eisen
    • 1
  • Miriam D. Hakim
    • 2
  1. 1.Dermatology Research Associates of CincinnatiCincinnatiUSA
  2. 2.University of Cincinnati Medical CenterCincinnatiUSA

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