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Acquired hypopigmentation disorders other than vitiligo

Mi Ryung Roh, MD, PhD
Sang Ho Oh, MD, PhD
Section Editor
Hensin Tsao, MD, PhD
Deputy Editor
Rosamaria Corona, MD, DSc


The color of human skin is mainly determined by the two types of melanin, the black-brown eumelanin and the yellow-red pheomelanin. Other significant contributors include the capillary blood flow, chromophores such as carotene or lycopene, and the collagen content of the dermis. Altered skin pigmentation can result from increased or decreased melanin, abnormal melanin distribution, decreased hemoglobin, or deposition of exogenous substances [1].

While hypopigmentation is a general term that refers to any form of decreased or absent skin pigmentation, hypomelanosis more specifically refers to a reduction of epidermal melanin. Hypopigmentation disorders may be congenital or acquired, diffuse (generalized) or localized, and may occur in isolation or be associated with a wide range of congenital or acquired disorders [2,3].

This topic will review the acquired hypopigmentation disorders other than vitiligo. Vitiligo is discussed separately. Hyperpigmentation disorders are also discussed separately. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis" and "Vitiligo: Management and prognosis" and "Approach to the patient with hyperpigmentation disorders".)


The diagnosis of hypopigmentation disorders is in many cases made on clinical grounds, based upon a detailed medical history and physical examination. The lesion morphology, color (hypopigmented or depigmented), distribution, and pattern are important clues to the diagnosis. However, examination with a Wood’s light, a skin biopsy, and additional laboratory tests may be required if the clinical diagnosis is uncertain. The differential diagnosis of hypopigmentation disorders is illustrated in the algorithm (algorithm 1).

Patient evaluation — The initial patient evaluation involves a detailed family and personal history and a complete physical examination, which should include a careful search for additional cutaneous and extracutaneous signs and symptoms.


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Literature review current through: Sep 2016. | This topic last updated: Jul 25, 2016.
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  1. Lapeere H, Boone B, De Schepper S, et al. Hypomelanoses and hypermelanoses. In: Fitzpatrick's Dermatology in General Medicine, 8th ed, Goldsmith L, Katz SI, Gilchrest BA, et al (Eds), McGraw-Hill Medical, New York 2012. p.804.
  2. Tey HL. Approach to hypopigmentation disorders in adults. Clin Exp Dermatol 2010; 35:829.
  3. Tey HL. A practical classification of childhood hypopigmentation disorders. Acta Derm Venereol 2010; 90:6.
  4. Gupta LK, Singhi MK. Wood's lamp. Indian J Dermatol Venereol Leprol 2004; 70:131.
  5. Ghosh S, Mukhopadhyay S. Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country. Br J Dermatol 2009; 160:40.
  6. Ghosh S. Chemical leukoderma: what's new on etiopathological and clinical aspects? Indian J Dermatol 2010; 55:255.
  7. Lerner EA, Sober AJ. Chemical and pharmacologic agents that cause hyperpigmentation or hypopigmentation of the skin. Dermatol Clin 1988; 6:327.
  8. Bonamonte D, Foti C, Romita P, et al. Colors and contact dermatitis. Dermatitis 2014; 25:155.
  9. English JS, Dawe RS, Ferguson J. Environmental effects and skin disease. Br Med Bull 2003; 68:129.
  10. Schwartz C, Javvaji S, Feinberg JS. Linear rays of hypopigmentation following intra-articular corticosteroid injection for post-traumatic degenerative joint disease. Dermatol Online J 2012; 18:11.
  11. Shah CP, Rhee D, Garg SJ. Eyelid cutaneous hypopigmentation after sub-tenon triamcinolone injection after retinal detachment repair. Retin Cases Brief Rep 2012; 6:271.
  12. Jalalat SZ, Cohen PR. Gefitinib-associated vitiligo: report in a man with parotid squamous cell carcinoma and review of drug-induced hypopigmentation. Dermatol Online J 2013; 19:20020.
  13. Llamas-Velasco M, Fraga J, Kutzner H, et al. Hypopigmented macules secondary to imatinib for the treatment of chronic myeloid leukemia: a histopathologic and immunohistochemical study. J Cutan Pathol 2014; 41:417.
  14. Aleem A. Hypopigmentation of the skin due to imatinib mesylate in patients with chronic myeloid leukemia. Hematol Oncol Stem Cell Ther 2009; 2:358.
  15. Arya V, Bansal M, Girard L, et al. Vitiligo at Injection Site of PEG-IFN-α 2a in Two Patients with Chronic Hepatitis C: Case Report and Literature Review. Case Rep Dermatol 2010; 2:156.
  16. Burnett CT, Kouba DJ. Imiquimod-induced depigmentation: report of two cases and review of the literature. Dermatol Surg 2012; 38:1872.
  17. Li W, Xin H, Ge L, et al. Induction of vitiligo after imiquimod treatment of condylomata acuminata. BMC Infect Dis 2014; 14:329.
  18. Ghasri P, Gattu S, Saedi N, Ganesan AK. Chemical leukoderma after the application of a transdermal methylphenidate patch. J Am Acad Dermatol 2012; 66:e237.
  19. Weyant GW, Chung CG, Helm KF. Halo nevus: review of the literature and clinicopathologic findings. Int J Dermatol 2015; 54:e433.
  20. Botella-Estrada R, Kutzner H. Study of the immunophenotype of the inflammatory cells in melanomas with regression and halo nevi. Am J Dermatopathol 2015; 37:376.
  21. Rosenberg SA, White DE. Vitiligo in patients with melanoma: normal tissue antigens can be targets for cancer immunotherapy. J Immunother Emphasis Tumor Immunol 1996; 19:81.
  22. Yang Y, Lin X, Fu W, et al. An approach to the correlation between vitiligo and autoimmune thyroiditis in Chinese children. Clin Exp Dermatol 2010; 35:706.
  23. Boasberg PD, Hoon DS, Piro LD, et al. Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma. J Invest Dermatol 2006; 126:2658.
  24. Hartmann A, Bedenk C, Keikavoussi P, et al. Vitiligo and melanoma-associated hypopigmentation (MAH): shared and discriminative features. J Dtsch Dermatol Ges 2008; 6:1053.
  25. Quaglino P, Marenco F, Osella-Abate S, et al. Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study. Ann Oncol 2010; 21:409.
  26. Naveh HP, Rao UN, Butterfield LH. Melanoma-associated leukoderma - immunology in black and white? Pigment Cell Melanoma Res 2013; 26:796.
  27. Boissy RE, Manga P. On the etiology of contact/occupational vitiligo. Pigment Cell Res 2004; 17:208.
  28. Westerhof W, d'Ischia M. Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 2007; 20:345.
  29. Vachiramon V, Thadanipon K. Postinflammatory hypopigmentation. Clin Exp Dermatol 2011; 36:708.
  30. Grimes PE, Bhawan J, Kim J, et al. Laser resurfacing-induced hypopigmentation: histologic alterations and repigmentation with topical photochemotherapy. Dermatol Surg 2001; 27:515.
  31. In SI, Yi SW, Kang HY, et al. Clinical and histopathological characteristics of pityriasis alba. Clin Exp Dermatol 2009; 34:591.
  32. Miazek N, Michalek I, Pawlowska-Kisiel M, et al. Pityriasis Alba--Common Disease, Enigmatic Entity: Up-to-Date Review of the Literature. Pediatr Dermatol 2015; 32:786.
  33. Blessmann Weber M, Sponchiado de Avila LG, Albaneze R, et al. Pityriasis alba: a study of pathogenic factors. J Eur Acad Dermatol Venereol 2002; 16:463.
  34. Rigopoulos D, Gregoriou S, Charissi C, et al. Tacrolimus ointment 0.1% in pityriasis alba: an open-label, randomized, placebo-controlled study. Br J Dermatol 2006; 155:152.
  35. Al-Mutairi N, Hadad AA. Efficacy of 308-nm xenon chloride excimer laser in pityriasis alba. Dermatol Surg 2012; 38:604.
  36. Sanchez M, Haimovic A, Prystowsky S. Sarcoidosis. Dermatol Clin 2015; 33:389.
  37. Boulos S, Vaid R, Aladily TN, et al. Clinical presentation, immunopathology, and treatment of juvenile-onset mycosis fungoides: a case series of 34 patients. J Am Acad Dermatol 2014; 71:1117.
  38. Furlan FC, Sanches JA. Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology. An Bras Dermatol 2013; 88:954.
  39. Tolkachjov SN, Comfere NI. Hypopigmented mycosis fungoides: a clinical mimicker of vitiligo. J Drugs Dermatol 2015; 14:193.
  40. Ngo JT, Trotter MJ, Haber RM. Juvenile-onset hypopigmented mycosis fungoides mimicking vitiligo. J Cutan Med Surg 2009; 13:230.
  41. Lane TN, Parker SS. Pityriasis lichenoides chronica in black patients. Cutis 2010; 85:125.
  42. Gupta AK, Batra R, Bluhm R, et al. Skin diseases associated with Malassezia species. J Am Acad Dermatol 2004; 51:785.
  43. Crespo-Erchiga V, Florencio VD. Malassezia yeasts and pityriasis versicolor. Curr Opin Infect Dis 2006; 19:139.
  44. Ramos-e-Silva M, Rebello PF. Leprosy. Recognition and treatment. Am J Clin Dermatol 2001; 2:203.
  45. Talhari C, Talhari S, Penna GO. Clinical aspects of leprosy. Clin Dermatol 2015; 33:26.
  46. Farnsworth N, Rosen T. Endemic treponematosis: review and update. Clin Dermatol 2006; 24:181.
  47. Giacani L, Lukehart SA. The endemic treponematoses. Clin Microbiol Rev 2014; 27:89.
  48. Miranda MF, Bittencourt Mde J, Lopes Ida C, Cumino Sdo S. Leucoderma syphiliticum: a rare expression of the secondary stage diagnosed by histopathology. An Bras Dermatol 2010; 85:512.
  49. Kim SK, Kang HY, Lee ES, Kim YC. Clinical and histopathologic characteristics of nevus depigmentosus. J Am Acad Dermatol 2006; 55:423.
  50. Lee HS, Chun YS, Hann SK. Nevus depigmentosus: clinical features and histopathologic characteristics in 67 patients. J Am Acad Dermatol 1999; 40:21.
  51. Mountcastle EA, Diestelmeier MR, Lupton GP. Nevus anemicus. J Am Acad Dermatol 1986; 14:628.
  52. Greaves MW, Birkett D, Johnson C. Nevus anemicus: a unique catecholamine-dependent nevus. Arch Dermatol 1970; 102:172.
  53. Hernández-Martín A, García-Martínez FJ, Duat A, et al. Nevus anemicus: a distinctive cutaneous finding in neurofibromatosis type 1. Pediatr Dermatol 2015; 32:342.
  54. Sachs C, Lipsker D. Nevus Anemicus and Bier Spots in Tuberous Sclerosis Complex. JAMA Dermatol 2016; 152:217.
  55. Vaassen P, Rosenbaum T. Nevus Anemicus As an Additional Diagnostic Marker of Neurofibromatosis Type 1 in Childhood. Neuropediatrics 2016; 47:190.
  56. Mahajan VK, Khatri G, Singh R, et al. Bier spots: An uncommon cause of mottled skin. Indian Dermatol Online J 2015; 6:128.
  57. He A, Kwatra SG, Kim N, Braunstein I. Bier spots: a benign vascular anomaly. BMJ Case Rep 2016; 2016.
  58. Fan YM, Yang YP, Li W, Li SF. Bier spots: six case reports. J Am Acad Dermatol 2009; 61:e11.
  59. Lin HC, Chen CH, Su HY. Bier spots on legs associated with deep vein thrombosis during pregnancy. Taiwan J Obstet Gynecol 2015; 54:102.
  60. Dean SM, Zirwas M. Bier spots are an under-recognized cutaneous manifestation of lower extremity lymphedema: a case series and brief review of the literature. Ann Vasc Surg 2014; 28:1935.e13.
  61. Bessis D, Jeziorski É, Rigau V, et al. Bier anaemic spots, cyanosis with urticaria-like eruption (BASCULE) syndrome: a new entity? Br J Dermatol 2016; 175:218.
  62. Bessis D, Dereure O, Rivire S, et al. Diffuse Bier white spots revealing cryoglobulinaemia. Br J Dermatol 2002; 146:921.
  63. Shin MK, Jeong KH, Oh IH, et al. Clinical features of idiopathic guttate hypomelanosis in 646 subjects and association with other aspects of photoaging. Int J Dermatol 2011; 50:798.
  64. Falabella R, Escobar C, Giraldo N, et al. On the pathogenesis of idiopathic guttate hypomelanosis. J Am Acad Dermatol 1987; 16:35.
  65. Whitehead WJ, Moyer DG, Vander Ploeg DE. Idiopathic guttate hypomelanosis. Arch Dermatol 1966; 94:279.
  66. Cummings KI, Cottel WI. Idiopathic guttate hypomelanosis. Arch Dermatol 1966; 93:184.
  67. Ortonne JP, Perrot H. Idiopathic guttate hypomelanosis. Ultrastructural study. Arch Dermatol 1980; 116:664.
  68. Kim SK, Kim EH, Kang HY, et al. Comprehensive understanding of idiopathic guttate hypomelanosis: clinical and histopathological correlation. Int J Dermatol 2010; 49:162.
  69. Joshi R. Skip areas of retained melanin: a clue to the histopathological diagnosis of idiopathic guttate hypomelanosis. Indian J Dermatol 2014; 59:571.
  70. Kakepis M, Havaki S, Katoulis A, et al. Idiopathic guttate hypomelanosis: an electron microscopy study. J Eur Acad Dermatol Venereol 2015; 29:1435.
  71. Asawanonda P, Sutthipong T, Prejawai N. Pimecrolimus for idiopathic guttate hypomelanosis. J Drugs Dermatol 2010; 9:238.
  72. Rerknimitr P, Disphanurat W, Achariyakul M. Topical tacrolimus significantly promotes repigmentation in idiopathic guttate hypomelanosis: a double-blind, randomized, placebo-controlled study. J Eur Acad Dermatol Venereol 2013; 27:460.
  73. Chitvanich S, Rerknimitr P, Panchaprateep R, et al. Combination of non-ablative fractional photothermolysis and 0.1% tacrolimus ointment is efficacious for treating idiopathic guttate hypomelanosis. J Dermatolog Treat 2016; 27:456.
  74. Shin J, Kim M, Park SH, Oh SH. The effect of fractional carbon dioxide lasers on idiopathic guttate hypomelanosis: a preliminary study. J Eur Acad Dermatol Venereol 2013; 27:e243.
  75. Rerknimitr P, Chitvanich S, Pongprutthipan M, et al. Non-ablative fractional photothermolysis in treatment of idiopathic guttate hypomelanosis. J Eur Acad Dermatol Venereol 2015; 29:2238.
  76. Goldust M, Mohebbipour A, Mirmohammadi R. Treatment of idiopathic guttate hypomelanosis with fractional carbon dioxide lasers. J Cosmet Laser Ther 2013.
  77. Ravikiran SP, Sacchidanand S, Leelavathy B. Therapeutic wounding - 88% phenol in idiopathic guttate hypomelanosis. Indian Dermatol Online J 2014; 5:14.
  78. Kumarasinghe SP. 3-5 second cryotherapy is effective in idiopathic guttate hypomelanosis. J Dermatol 2004; 31:437.
  79. Relyveld GN, Menke HE, Westerhof W. Progressive macular hypomelanosis: an overview. Am J Clin Dermatol 2007; 8:13.
  80. Westerhof W, Relyveld GN, Kingswijk MM, et al. Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis. Arch Dermatol 2004; 140:210.
  81. de Morais Cavalcanti SM, de França ER, Magalhães M, et al. A quantitative analysis of Propionibacterium acnes in lesional and non-lesional skin of patients with progressive macular hypomelanosis by real-time polymerase chain reaction. Braz J Microbiol 2011; 42:423.
  82. Relyveld GN, Westerhof W, Woudenberg J, et al. Progressive macular hypomelanosis is associated with a putative Propionibacterium species. J Invest Dermatol 2010; 130:1182.
  83. Guillet G, Helenon R, Gauthier Y, et al. Progressive macular hypomelanosis of the trunk: primary acquired hypopigmentation. J Cutan Pathol 1988; 15:286.
  84. Relyveld GN, Dingemans KP, Menke HE, et al. Ultrastructural findings in progressive macular hypomelanosis indicate decreased melanin production. J Eur Acad Dermatol Venereol 2008; 22:568.
  85. Wu XG, Xu AE, Song XZ, et al. Clinical, pathologic, and ultrastructural studies of progressive macular hypomelanosis. Int J Dermatol 2010; 49:1127.
  86. Kim MB, Kim GW, Cho HH, et al. Narrowband UVB treatment of progressive macular hypomelanosis. J Am Acad Dermatol 2012; 66:598.
  87. Relyveld GN, Kingswijk MM, Reitsma JB, et al. Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: a randomized study. J Am Acad Dermatol 2006; 55:836.
  88. Sim JH, Lee DJ, Lee JS, Kim YC. Comparison of the clinical efficacy of NBUVB and NBUVB with benzoyl peroxide/clindamycin in progressive macular hypomelanosis. J Eur Acad Dermatol Venereol 2011; 25:1318.
  89. Santos JB, Almeida OL, Silva LM, Barreto ER. Efficacy of topical combination of benzoyl peroxide 5% and clindamycin 1% for the treatment of progressive macular hypomelanosis: a randomized, doubleblind, placebo-controlled trial. An Bras Dermatol 2011; 86:50.
  90. Falabella R, Escobar CE, Carrascal E, Arroyave JA. Leukoderma punctata. J Am Acad Dermatol 1988; 18:485.
  91. Fernandes NC, Pina JC. Leukoderma punctata following topical PUVAsol treatment. An Bras Dermatol 2010; 85:571.
  92. Dogra S, Jain R, Parsad D, Handa S. Leukoderma punctatum following systemic PUVA therapy. Int J Dermatol 2002; 41:922.
  93. Park JH, Lee MH. Case of leukoderma punctata after topical PUVA treatment. Int J Dermatol 2004; 43:138.
  94. McKenzie CA, Wakamatsu K, Hanchard NA, et al. Childhood malnutrition is associated with a reduction in the total melanin content of scalp hair. Br J Nutr 2007; 98:159.
  95. Friedman PS. Metabolic, nutritional, and endocrine disorders. In: The Pigmentary System: Physiology and Pathophysiology, Nordlund JJ, Boissy RE, Hearing VJ, et al (Eds), Blackwell Publishing, Malden 2006. p.664.
  96. Brooks VE, Richards R. Depigmentation in Cushing's syndrome. Arch Intern Med 1966; 117:677.
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