- Author: Vlada Groysman, MD; Chief Editor: Dirk M Elston, MD more...
Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes that is characterized by circumscribed, depigmented macules and patches. The condition is frequently associated with disorders of autoimmune origin, with thyroid abnormalities being the most common. See the image below.
Signs and symptoms
Vitiligo lesions are characterized as follows:
White or hypopigmented
Usually well demarcated
Round, oval, or linear in shape
Borders may be convex 
Range from millimeters to centimeters in size
Enlarge centrifugally over time at an unpredictable rate
Initial lesions occur most frequently on the hands, forearms, feet, and face, favoring a perioral and periocular distribution.
Trichrome vitiligo: An intermediate zone of hypochromia is located between the achromic center and the peripheral unaffected skin; the natural evolution of the hypopigmented areas is progression to full depigmentation, resulting in 3 shades of color—brown, tan, and white—in the same patient
Marginal inflammatory vitiligo: Lesions have a red, raised border, which is present from the onset of vitiligo (in rare cases) or may appear several months or years after the initial onset; mild pruritus may be present
Quadrichrome vitiligo: Reflects the presence of a fourth color (ie, dark brown) at sites of perifollicular repigmentation 
Blue vitiligo: Results in blue coloration of vitiligo macules
Koebner phenomenon: Development of vitiligo in sites of specific trauma, such as a cut, burn, or abrasion
Vitiligo can be classified as follows:
Localized vitiligo can exist in the following forms:
Focal: Characterized by 1 or more macules in 1 area, most commonly in the distribution of the trigeminal nerve
Segmental: Manifests as 1 or more macules in a dermatomal or quasidermatomal pattern; occurs most commonly in children; more than half the patients with segmental vitiligo have patches of white hair or poliosis
Mucosal: Mucous membranes alone are affected
Generalized vitiligo can manifest as the following:
Acrofacial: Depigmentation occurs on the distal fingers and periorificial areas
Vulgaris: Characterized by scattered patches that are widely distributed
Mixed: Acrofacial and vulgaris vitiligo occur in combination, or segmental and acrofacial vitiligo and/or vulgaris involvement are noted in combination
Universal vitiligo results in complete or nearly complete depigmentation. It is often associated with multiple endocrinopathy syndrome.
See Clinical Presentation for more detail.
Although the diagnosis of vitiligo generally is made on the basis of clinical findings, biopsy is occasionally helpful for differentiating vitiligo from other hypopigmentary disorders.
Microscopic examination of involved skin shows a complete absence of melanocytes in association with a total loss of epidermal pigmentation. Superficial perivascular and perifollicular lymphocytic infiltrates may be observed at the margin of vitiliginous lesions, consistent with a cell-mediated process destroying melanocytes.
Other documented histologic findings include the following:
Degenerative changes in keratinocytes and melanocytes in the border lesions and adjacent skin
Increased numbers of Langerhans cells
Thickening of the basement membrane
Loss of pigment and melanocytes in the epidermis is highlighted by Fontana-Masson staining and immunohistochemistry testing.[3, 4]
See Workup for more detail.
Systemic phototherapy: Induces cosmetically satisfactory repigmentation in up to 70% of patients with early or localized disease 
Laser therapy: Effective on limited, stable patches of vitiligo
Steroid therapy: Systemic steroids (prednisone) have been used, although prolonged use and their toxicity are undesirable 
Depigmentation therapy: If vitiligo is widespread and attempts at repigmentation have not produced satisfactory results, depigmentation may be attempted in selected patients
Micropigmentation: Tattooing can be used to repigment depigmented skin in dark-skinned individuals
The basic types of repigmentation surgery are as follow[7, 8] :
Noncultured epidermal suspensions
Thin dermoepidermal grafts
Suction epidermal grafting
Cultured epidermis with melanocytes or cultured melanocyte suspensions
Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes, and it is characterized by circumscribed depigmented macules and patches. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. Vitiligo affects 0.5-2% of the world population, and the average age of onset is 20 years.
Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and nongenetic factors. Although several theories have been proposed about the pathogenesis of vitiligo, the precise cause remains unknown. Generally agreed upon principles are an absence of functional melanocytes in vitiligo skin and a loss of histochemically recognized melanocytes, owing to their destruction. However, the destruction is most likely a slow process resulting in a progressive decrease of melanocytes. Theories regarding destruction of melanocytes include autoimmune mechanisms, cytotoxic mechanisms, an intrinsic defect of melanocytes, oxidant-antioxidant mechanisms, and neural mechanisms.
Autoimmune destruction of melanocytes
The autoimmune theory proposes alteration in humoral and cellular immunity in the destruction of melanocytes of vitiligo. Thyroid disorders, particularly Hashimoto thyroiditis and Graves disease; other endocrinopathies, such as Addison disease and diabetes mellitus; and alopecia areata; pernicious anemia; inflammatory bowel disease; psoriasis; and autoimmune polyglandular syndrome are all associated with vitiligo.
The most convincing evidence of an autoimmune pathogenesis is the presence of circulating antibodies in patients with vitiligo. The role of humoral immunity is further supported by the observation that melanocytes are destroyed in healthy skin engrafted onto nude mice injected with vitiligo patient sera.
In addition to the involvement of humoral immune mechanisms in the pathogenesis of vitiligo, strong evidence indicates involvement of cellular immunity in vitiligo. Destruction of melanocytes may be directly mediated by autoreactive CD8+ T cells. Activated CD8+ T cells have been demonstrated in perilesional vitiligo skin. In addition, melanocyte-specific T cells have been detected in peripheral blood of patients with autoimmune vitiligo.[12, 13]
Intrinsic defect of melanocytes
Vitiligo melanocytes may have an intrinsic defect leading to melanocyte death. These melanocytes demonstrate various abnormalities, including abnormal, rough endoplasmic reticulum and incompetent synthesis and processing of melanocytes. In addition, homing-receptor dysregulation has also been detected. Early apoptosis of melanocytes has also been suggested as a cause of reduced melanocyte survival; however, subsequent investigation found that the relative apoptosis susceptibility of vitiligo melanocytes was comparable with that of normal control pigment cells.
Disturbance in oxidant-antioxidant system in vitiligo
Oxidant stress may also play an essential role in the pathogenesis of vitiligo. Studies suggest that accumulation of free radicals toxic to melanocytes leads to their destruction. Because patients with vitiligo exhibit a characteristic yellow/green or bluish fluorescence in clinically affected skin, this led to the discovery that the fluorescence is due to accumulation of 2 different oxidized pteridines. The overproduction of pteridines led to the discovery of a metabolic defect in tetrahydrobiopterin homeostasis in patients with vitiligo, which results in the accumulation of melanocytotoxic hydrogen peroxide.
Because oxidative stress has been suggested to be the initial pathogenic event in melanocyte degeneration, several studies have been conducted to evaluate this theory. Recent investigations set out to evaluate the role of oxidative stress by measuring levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in lesional and normal skin of patients with vitiligo and in the skin of normal control subjects. They concluded oxidative stress is increased in vitiligo, as indicated by high levels of SOD and low levels of CAT in the skin of vitiligo patients.
Case reports describe patients afflicted with a nerve injury who also have vitiligo have hypopigmentation or depigmentation in denervated areas. Additionally, segmental vitiligo frequently occurs in a dermatomal pattern, which suggests that certain chemical mediators are released from nerve endings that affect melanin production. Further, sweating and vasoconstriction are increased in depigmented patches of vitiligo, implying an increase in adrenergic activity. Finally, increased urinary excretion of homovanillic acid and vanilmandelic acid (neurometabolites) has been documented in patients with vitiligo. This may be a secondary or primary phenomenon.
In summary, although the ultimate cause of vitiligo is not completely known, this condition does not reflect simple melanocyte loss, but possible immunologic alterations and other molecular defects leading to pigment cell destruction; however, melanocytes may be present in depigmented skin after years of onset and may still respond to medical therapy under appropriate stimulation.
Genetics of vitiligo
Vitiligo is characterized by incomplete penetrance, multiple susceptibility loci, and genetic heterogeneity. The inheritance of vitiligo may involve genes associated with the biosynthesis of melanin, a response to oxidative stress, and regulation of autoimmunity.
Human leukocyte antigens (HLAs) may be associated, but not in a consistent manner. For example, HLA-DR4 is increased in blacks, HLA-B13 is increased in Moroccan Jews, and HLA-B35 is increased in Yemenite Jews. An association with HLA-B13 is described in the presence of antithyroid antibodies.
A genome-wide association study of generalized vitiligo in an isolated European founder population identified that the group had significant association with single-nucleotide polymorphisms in a 30-kb LD block on band 6q27, in close vicinity to IDDM8, which is a linkage and an association signal for type I diabetes mellitus and rheumatoid arthritis. Only one gene, SMOC2, is in the region of association, within which SNP rs13208776 attained genome-wide significance for association with other autoimmune diseases and vitiligo.
The age of onset has a genetic component; in another genomewide association study, a quantitative locus for age of onset was found in the major histocompatibility complex class II region near a region associated with generalized vitiligo susceptibility.
In the United States, the relative rate of vitiligo is 1%.
Vitiligo is relatively common, with a rate of 1-2%. Approximately 30% of vitiligo cases occur with a familial clustering of cases.
A female preponderance has been reported for vitiligo, but it is not statistically significant and the discrepancy has been attributed to an increase in reporting of cosmetic concerns by female patients.
Vitiligo may appear at any time from birth to senescence, although the onset is most commonly observed in persons aged 10-30 years.
Vitiligo rarely is seen in infancy or old age. Nearly all cases of vitiligo are acquired relatively early in life.
The average age of onset for vitiligo is approximately 20 years. The age of onset is unlikely to vary between the sexes.
Heightened concern about the appearance of the skin may contribute to an early awareness of vitiligo among females.
Ortonne J. Vitiligo and other disorders of Hypopigmentation. Bolognia J, Jorizzo J, Rapini R, eds. Dermatology. 2nd. Spain: Elsevier; 2008. Vol 1: 65.
Kovacs SO. Vitiligo. J Am Acad Dermatol. 1998 May. 38(5 Pt 1):647-66; quiz 667-8. [Medline].
McKee P, Calonje E, Granter S, eds. Disorders of Pigmentation. Pathology of the Skin with Clinical Correlations. 3rd ed. China: Elsevier Mosby; 2005. Vol 2: 993-7.
Moellmann G, Klein-Angerer S, Scollay DA, Nordlund JJ, Lerner AB. Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol. 1982 Nov. 79(5):321-30. [Medline].
Matz H, Tur E. Vitiligo. Curr Probl Dermatol. 2007. 35:78-102. [Medline].
Lotti T, Gori A, Zanieri F, Colucci R, Moretti S. Vitiligo: new and emerging treatments. Dermatol Ther. 2008 Mar-Apr. 21(2):110-7. [Medline].
van Geel N, Ongenae K, Naeyaert JM. Surgical techniques for vitiligo: a review. Dermatology. 2001. 202(2):162-6. [Medline].
Rusfianti M, Wirohadidjodjo YW. Dermatosurgical techniques for repigmentation of vitiligo. Int J Dermatol. 2006 Apr. 45(4):411-7. [Medline].
Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun. 2008. 10:227-43. [Medline].
Toussaint S, Kamino H. Noninfectous papular and squamous diseases. Elder D, Elenitas R, Jaworsky D, Johnson B Jr. Lever's Histopathology of the Skin. Philadelphia, Pa: Lippincot-Raven; 1997. 154-5.
Schallreuter KU, Wood JM, Pittelkow MR, et al. Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin. Science. 1994 Mar 11. 263(5152):1444-6. [Medline].
Ongenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res. 2003 Apr. 16(2):90-100. [Medline].
Zhang BX, Lin M, Qi XY, Zhang RX, Wei ZD, Zhu J, et al. Characterization of circulating CD8+T cells expressing skin homing and cytotoxic molecules in active non-segmental vitiligo. Eur J Dermatol. 2013 Jun 19. [Medline].
van den Wijngaard RM, Aten J, Scheepmaker A, et al. Expression and modulation of apoptosis regulatory molecules in human melanocytes: significance in vitiligo. Br J Dermatol. 2000 Sep. 143(3):573-81. [Medline].
Sravani PV, Babu NK, Gopal KV, Rao GR, Rao AR, Moorthy B. Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non-vitiliginous skin. Indian J Dermatol Venereol Leprol. 2009 May-Jun. 75(3):268-71. [Medline].
Spritz RA. The genetics of generalized vitiligo. Curr Dir Autoimmun. 2008. 10:244-57. [Medline].
Halder R, Taliaferro S. Vitiligo. Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller A, Lefell D, eds. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. Vol 1: 72.
Birlea SA, Gowan K, Fain PR, Spritz RA. Genome-Wide Association Study of Generalized Vitiligo in an Isolated European Founder Population Identifies SMOC2, in Close Proximity to IDDM8. J Invest Dermatol. 2009 Nov 5. [Medline].
Jin Y, Birlea SA, Fain PR, et al. Genome-Wide Analysis Identifies a Quantitative Trait Locus in the MHC Class II Region Associated with Generalized Vitiligo Age of Onset. J Invest Dermatol. 2011 Jun. 131(6):1308-12. [Medline].
Hann S-K. Clinical variants of vitiligo. Lotti T, Hercogova J, eds. Vitiligo: Problems and Solutions. New York, NY: Marcel Dekker; 2004. 159-73.
Ezzedine K, Diallo A, Leaute-Labreze C, et al. Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients. Br J Dermatol. 2011 Jul. 165(1):44-9. [Medline].
Yang Y, Lin X, Fu W, Luo X, Kang K. An approach to the correlation between vitiligo and autoimmune thyroiditis in Chinese children. Clin Exp Dermatol. 2009 Oct 23. [Medline].
Rashtak S, Pittelkow MR. Skin involvement in systemic autoimmune diseases. Curr Dir Autoimmun. 2008. 10:344-58. [Medline].
Pajvani U, Ahmad N, Wiley A, et al. The relationship between family medical history and childhood vitiligo. J Am Acad Dermatol. 2006 Aug. 55(2):238-44. [Medline].
Aydogan K, Turan OF, Onart S, Karadogan SK, Tunali S. Audiological abnormalities in patients with vitiligo. Clin Exp Dermatol. 2006 Jan. 31(1):110-3. [Medline].
Ardiç FN, Aktan S, Kara CO, Sanli B. High-frequency hearing and reflex latency in patients with pigment disorder. Am J Otolaryngol. 1998 Nov-Dec. 19(6):365-9. [Medline].
Gul U, Kilic A, Tulunay O, Kaygusuz G. Vitiligo associated with malignant melanoma and lupus erythematosus. J Dermatol. 2007 Feb. 34(2):142-5. [Medline].
Ohguchi R, Kato H, Furuhashi T, Nakamura M, Nishida E, Watanabe S, et al. Risk factors and treatment responses in patients with vitiligo in Japan-A retrospective large-scale study. Kaohsiung J Med Sci. 2015 May. 31 (5):260-4. [Medline].
Schallreuter KU, Bahadoran P, Picardo M, et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else?. Exp Dermatol. 2008 Feb. 17(2):139-40; discussion 141-60. [Medline].
Elgoweini M, Nour El Din N. Response of vitiligo to narrowband ultraviolet B and oral antioxidants. J Clin Pharmacol. 2009 Jul. 49(7):852-5. [Medline].
Menchini G, Lotti T, Tsoureli-Nikita E. UV-B narrowband micro phototherapy. Lotti T, Hercogova J, eds. Vitiligo: Problems and Solutions. New York, NY: Marcel Dekker; 2004. 323-34.
Passeron T, Ostovari N, Zakaria W, et al. Topical tacrolimus and the 308-nm excimer laser: a synergistic combination for the treatment of vitiligo. Arch Dermatol. 2004 Sep. 140(9):1065-9. [Medline].
Lotti T, Prignano F, Buggiani G. New and experimental treatments of vitiligo and other hypomelanoses. Dermatol Clin. 2007 Jul. 25(3):393-400, ix. [Medline].
Bae JM, Yoo HJ, Kim H, Lee JH, Kim GM. Combination therapy with 308-nm excimer laser, topical tacrolimus, and short-term systemic corticosteroids for segmental vitiligo: A retrospective study of 159 patients. J Am Acad Dermatol. 2015 May 6. [Medline].
Do JE, Shin JY, Kim DY, Hann SK, Oh SH. The effect of 308 nm excimer laser on segmental vitiligo: a retrospective study of 80 patients with segmental vitiligo. Photodermatol Photoimmunol Photomed. 2011 Jun. 27(3):147-51. [Medline].
Esfandiarpour I, Ekhlasi A, Farajzadeh S, Shamsadini S. The efficacy of pimecrolimus 1% cream plus narrow-band ultraviolet B in the treatment of vitiligo: a double-blind, placebo-controlled clinical trial. J Dermatolog Treat. 2009. 20(1):14-8. [Medline].
Njoo MD, Westerhof W. Therapeutic guidelines for vitiligo. Lotti T, Hercogova J, eds. Vitiligo: Problems and Solutions. New York, NY: Marcel Dekker; 2004. 235-52.
Farajzadeh S, Daraei Z, Esfandiarpour I, Hosseini SH. The efficacy of pimecrolimus 1% cream combined with microdermabrasion in the treatment of nonsegmental childhood vitiligo: a randomized placebo-controlled study. Pediatr Dermatol. 2009 May-Jun. 26(3):286-91. [Medline].
Birlea SA, Costin GE, Norris DA. Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr. 9(4):345-59. [Medline].
Saraceno R, Nistico SP, Capriotti E, Chimenti S. Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study. Dermatol Ther. 2009 Jul-Aug. 22(4):391-4. [Medline].
Grau C, Silverberg NB. Vitiligo patients seeking depigmentation therapy: a case report and guidelines for psychological screening. Cutis. 2013 May. 91(5):248-52. [Medline].
Chimento SM, Newland M, Ricotti C, Nistico S, Romanelli P. A pilot study to determine the safety and efficacy of monochromatic excimer light in the treatment of vitiligo. J Drugs Dermatol. 2008 Mar. 7(3):258-63. [Medline].
Falabella R. Surgical approaches for stable vitiligo. Dermatol Surg. 2005 Oct. 31(10):1277-84. [Medline].
van Geel N, Wallaeys E, Goh BK, De Mil M, Lambert J. Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus. Br J Dermatol. 2010 Dec. 163(6):1186-93. [Medline].
Gou D, Currimbhoy S, Pandya AG. Suction blister grafting for vitiligo: efficacy and clinical predictive factors. Dermatol Surg. 2015 May. 41 (5):633-9. [Medline].
McGovern TW, Bolognia J, Leffell DJ. Flip-top pigment transplantation: a novel transplantation procedure for the treatment of depigmentation. Arch Dermatol. 1999 Nov. 135(11):1305-7. [Medline].
Fongers A, Wolkerstorfer A, Nieuweboer-Krobotova L, Krawczyk P, Toth GG, van der Veen JP. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity. Br J Dermatol. 2009 Nov. 161(5):1105-11. [Medline].