Skip to main content
NCBI home page
Indian Journal of Dermatology logoLink to Indian Journal of Dermatology
. 2011 Mar-Apr;56(2):180–189. doi: 10.4103/0019-5154.80413

VITILIGO: A REVIEW OF SOME FACTS LESSER KNOWN ABOUT DEPIGMENTATION

James J Nordlund 1,✉
PMCID: PMC3108518  PMID: 21716544

Abstract

Vitiligo is a disorder that causes the destruction of melanocytes. It has three important factors underlying this destruction. The depigmented skin has many aberrant functions such as a muted response to contact allergens, a phenomenon also seen in mice that depigment. The white skin of those with vitiligo does not form non-melanoma skin cancers although the white skin of albinos, which has a similar color as vitiligo, is highly susceptible to skin cancer.

Keywords: Vitiligo, contact allergen, non-melanoma skin cancer, albinos

Introduction

Vitiligo is a common and easily recognized disorder for all dermatologists, many physicians and some observant members of the general public. It is a disorder that is characterized by white spots typically first noted on the fingers, knuckles, around the eyes and mouth, and on the feet and genitalia[1,2] [Figures 1–3]. There are two basic mechanisms whereby the skin can become white.[3] Melanin is synthesized by melanocytes within melanosomes that are transferred into the surrounding keratinocytes. The keratinocytes transport the melanin and melanosomes from the basal layer of the epidermis to the stratum corneum where they are desquamated into the environment.[4] Some disorders inhibit or retard the production of melanin formation and the skin develops hypopigmentation.[3] Such disorders include, among many others, oculocutaneous albinism, pityriasis alba, tinea versicolor and nevus depigmentosus. In these disorders, melanocytes are present in normal numbers in the epidermis but produce less than normal amounts of melanin. Typically, the skin exhibits mild to marked hypopigmentation.

Figure 1.

Figure 1

Open in a new tab

Depigmentation of the fingers and dorsum of the hands, classical, early manifestations of vitiligo

Figure 3.

Figure 3

Open in a new tab

Depigmentation around the eyes (partially blocked), the nares and mouth, all classical and early manifestations of bilateral vitiligo

Figure 2.

Figure 2

Open in a new tab

Depigmentation of the feet, typical early manifestation of vitiligo

In contrast, other types of leukoderma are characterized by the absence of melanocytes and therefore, complete absence of melanin. Such disorders include piebaldism, the leukoderma of lupus erythematosus and other scarring disorders, and vitiligo. These types of leukoderma typically are totally depigmented. Vitiligo and lupus cause a destruction of melanocytes during postnatal life. Piebaldism affects the migration of melanocytes during embryogenesis and the infant is born with depigmentation of the hair and skin.

There seem to be three major factors involved in the destruction of melanocytes in patients with vitiligo.[5] The first is that vitiligo patients inherit a set of three “vitiligo” genes which predisposes them to destruction of melanocytes.[6–8] There probably are many different sets of three genes that can cause vitiligo so that not every individual would necessarily inherit the same three. The second abnormality relates to the melanocytes themselves. Melanocytes from patients with vitiligo differ from those obtained from a person without vitiligo. For example, vitiligo melanocytes require different and more fastidious culture conditions than those from normal individuals.[9–11] Also, vitiligo melanocytes are much more sensitive to phenolic chemicals than normal melanocytes and readily undergo apoptosis when exposed to such agents.[12,13] The third factor is an environmental agent(s) that activates (or inhibits) the genes involved, thereby setting in motion the process of destruction of the susceptible melanocytes. The vitiligo genes activated (inhibited) by the environmental agents seem to cause an excessive immune reaction that induces melanocytes to undergo apoptosis,[14–20] and depigmentation of the skin results.

Vitiligo principally affects melanocytes. However, keratinocytes also manifest some damage, mostly a granular degeneration.[21] It is not widely recognized that Merkel cells also are absent from depigmented skin.[22–24] The significance of this absence and the impact it has on the function of the epidermis are not known. The cells of the epidermis, i.e., keratinocytes, Langerhans cells, melanocytes and Merkel cells, work closely together.[25] It should be expected that loss of one or the other cells from the epidermis would alter its function. It is thought the Merkel cell functions as a neurosensory cell. It has been shown that sweating and bleeding times are altered in the depigmented skin of a patient with vitiligo.[26,27] Alterations in cholinergic activity and morphology of sweat glands which are innervated by cholinergic sympathetic nerves have been observed by some investigators[28,29] although not by all observers.[30,31] The functional changes observed in depigmented skin might be related to the collateral damage to keratinocytes and/or Merkel cells. There are other functional abnormalities in vitiliginous skin which will be discussed later.

There are two main types of vitiligo, unilateral (often called segmental) and bilateral (usually termed generalized). Segmental vitiligo will be discussed later. However, the word “segmental” is often confused with the term “dermatomal”, the latter meaning the pattern of sensory innervation of the skin. Segmental is rarely, if ever, dermatomal, so unilateral is a better term to avoid confusion.

Bilateral or generalized vitiligo can begin at any age and tends to progress intermittently over the life of the patient. It produces depigmentation that is remarkably symmetrical in distribution [Figures 1–4]. A patch on the right side of the body is matched by a patch in a similar location on the left side. The entire body can depigment although it rarely does so. The classical presentation of the depigmentation is a remarkably symmetrical distribution of depigmentation beginning on the fingers, feet, wrists, elbows, axillae and around the mouth and eyes. There is no explanation for this symmetry. Yet, it is so typical and common that symmetrical depigmentation is one criterion for the diagnosis of vitiligo. (Depigmented patches can be randomly scattered. This has been labeled atypical vitiligo.) Dr. RB Goudie, a Scottish pathologist, was intrigued by the symmetry that characterized vitiligo. He noted that the distribution of some autoimmune endocrine disorders such as thyrotoxicosis resembled in some ways the distribution of vitiligo.[32,33] He also noted that malignant lymphomas often appeared as tumors symmetrically involving both sides of the body. He hypothesized that benign lymphocytes honed to specific sites in the skin where they might be responsible for the symmetry of vitiligo.[34] Although his ideas are no longer popular, they are based on the known propensity of cutaneous lymphocytes to migrate to specific sites in the skin and the role of lymphocytes in causing depigmentation. His ideas are worthy of reconsideration.

Figure 4.

Figure 4

Open in a new tab

Extensive depigmentation of a woman which illustrates the symmetrical distribution of classical bilateral vitiligo

Unilateral (segmental) vitiligo differs from generalized vitiligo in many important aspects. It more commonly begins in children and young adults and progresses for a limited period, usually 1–2 years, and then remains static for the life of the individual.[35] It affects just one side of the body [Figure 5]. In contrast to bilateral vitiligo, the distribution is asymmetrical on the skin. However, the patterns also are not random. The various sites affected by the depigmentation are repetitious. The patterns on the face have been classified.[36,37] There are patterns affecting the neck and trunk which resemble each other in location and shape [Figures 6–8]. It is important to note that a nevus depigmentosus [Figures 9 and 10] and a cafι-au-lait spot can have a similar shape, pattern and location as segmental vitiligo [Figures 11–13]. These similarities of patterns and distribution for unilateral vitiligo and nevus depigmentosus suggest that unilateral vitiligo corresponds to embryological developmental patterns for melanocytes in their migration from the neural crest to the epidermis.

Figure 5.

Figure 5

Open in a new tab

Unilateral (segmental) vitiligo affecting one side of the face of a young boy. Note that the depigmentation does not correspond to a dermatome

Figure 6.

Figure 6

Open in a new tab

Unilateral depigmentation (segmental vitiligo) affecting the neck of a woman. Note the very similar distribution of depigmentation in the two men pictured in Figures 7 and 8

Figure 8.

Figure 8

Open in a new tab

Unilateral depigmentation (segmental vitiligo) on the neck of a man with a distribution similar to that in Figures 6 and 7

Figure 9.

Figure 9

Open in a new tab

Nevus depigmentosus on the neck of a boy. The pigmentary abnormality was present at birth in the patient

Figure 10.

Figure 10

Open in a new tab

Nevus depigmentosus on the neck of a man. The pigmentary abnormality was present at birth in the patient

Figure 11.

Figure 11

Open in a new tab

Unilateral depigmentation (segmental vitiligo) on the anterior chest and upper part of the right arm in a young woman. The distribution of pigment loss is very similar in this patient and the one given in Figure 12

Figure 13.

Figure 13

Open in a new tab

A nevus depigmentosus in a young girl with a distribution of pigment loss similar to the unilateral vitiligo seen in Figures 11 and 12

Figure 7.

Figure 7

Open in a new tab

Unilateral depigmentation (segmental vitiligo) of the neck of a man which is similar to the depigmentation seen in Figures 6 and 8

Figure 12.

Figure 12

Open in a new tab

Unilateral depigmentation (segmental vitiligo) on the anterior chest and upper part of the right arm in a girl. The distribution of pigment loss is very similar in this patient and the one shown in Figure 11

Typically, bilateral vitiligo progresses over the life of the individual so that the person has partially normal and partially depigmented skin. This probably is the worst outcome. Of course, it is best to be one's own color but it is the worst condition for most people to have two colors at least on visible skin such as the hands, face, neck and arms. To avoid this, for some patients, the treatment of choice is depigmentation of the normal skin by applications of monobenzone by which they achieve a single color. This is what Michael Jackson did to achieve a single white color. Occasionally, nature achieves the same end. A very small number of patients will develop over a period of a few months a very rapid depigmentation of the entire integument and also the hair [Figure 14]. Dr. Aaron Lerner called it “veloce vitiligo” or rapid vitiligo. These individuals go from having dark skin to having totally depigmented skin and hair in a period of months. It can occur spontaneously but in my personal experience has followed in a few individuals generalized erythematous drug eruptions. How or why this happens is not known.

Figure 14.

Figure 14

Open in a new tab

An Indian woman with veloce vitiligo. She lost almost all of her pigmentation on the skin and hair over a period of some months

The three cells of the epidermis, keratinocytes, Langerhans cells and melanocytes, form a troika so to speak [Figure 15] and work together.[25] As noted above, it should not be surprising that depigmented skin has some altered functions if one part of the troika is missing. Several Japanese workers noted that depigmented skin of vitiligo patients did not react to sensitization with dinitrofluoro benzene (DNFB) to produce contact dermatitis.[38,39] In their experiments, DNFB was applied to normal skin to induce contact allergy. A challenge was applied to both normal and white skin. The white skin did not respond. In other experiments, the sensitizing dose of DNFB was applied to white skin and the challenge to both white and pigmented skin. The pigmented but not the white skin responded.[38] These findings suggest that the afferent limb of the immune response is intact in the white skin, but the efferent limb is not so. In the same studies, Candida antigen was injected into the dermis of both white and pigmented skin and the dermal response was normal in both.[39] The discrepancy between epidermal and dermal immune responses might be attributed to loss of the melanocytes which could have immune/inflammatory functions.[25,40]

Figure 15.

Figure 15

Open in a new tab

The epidermis is composed of three main cell types that work together like a troika

Others have noted that depigmented skin does not respond to contact allergens.[41–44] Monobenzone as noted above is used to depigment skin for those with depigmentation too widespread to repigment. Some individuals applying monobenzone develop a contact allergy to the medication [Figures 16 and 17]. However, the allergic dermatitis is manifested only in the pigmented skin.[45] In separate studies, investigators observed that the inflammatory response to irritants was abnormal in white skin compared to pigmented skin.[46] It seems especially fascinating that graft versus host skin disease in one individual with piebaldism affected preferentially the white skin,[47] emphasizing again that the three cells of the epidermis work together and that melanocytes likely play a role in inflammation.

Figure 16.

Figure 16

Open in a new tab

A woman treated with monobenzone, who developed a contact allergy. The dermatitis is exclusively confined to the pigmented skin

Figure 17.

Figure 17

Open in a new tab

A man treated with monobenzone, who developed a contact allergy. The dermatitis is exclusively confined to the pigmented skin

A muted response to contact allergens is not unique to humans. There is a species of mice that has an acquired form of depigmentation resembling vitiligo, called the mi/mivit/vit mouse [Figure 18].[48,49] The skin and follicles of the mouse have normal numbers of Langerhans cells in both the pigmented and depigmented stages.[50] However, the response of the mouse to potent contact allergens is highly muted after the skin and pelage have lost their melanocytes.[51,52] This aberrant response might be due to inability of depigmented skin to express intercellular adhesion molecule 1 (ICAM-1).[53] Humans with vitiligo show altered expression of ICAM-1 in the epidermis. ICAM-1 is critical to a normal immune response.[54,55]

Figure 18.

Figure 18

Open in a new tab

Mice with mivit/mivit gene. The mouse on the left has a piebald band on the leg but a normal pigmented pelage in early life. The mouse on the right is undergoing depigmentation with loss of melanocytes from the epidermis and hair follicles

One of the most mysterious features of vitiligo is the resistance of skin depigmented by vitiligo to producing skin cancers. It is a common worry for physicians and patients with vitiligo that they might get a melanoma. It is possible for a patient with vitiligo to get a melanoma but only in their normally pigmented skin.[56,57] The white skin is devoid of melanocytes[58] and thus unable to generate a melanoma. It is baffling that the white skin is also highly resistant to formation of keratinocyte malignancies, i.e., basal and squamous cell carcinomas.

Vitiligo skin is totally depigmented. The color is similar to that of albinism. Albinos are known to have a high incidence of skin cancer, especially in Africa where most albinos have oculocutaneous albinism type 2, a disorder caused by mutations in the p-gene.[59–65] Most of these are squamous cell carcinomas. Interestingly, few individuals with other forms of oculocutaneous albinism, types I, III and IV, have been reported to have skin cancer. There are many possible explanations for this, the most obvious being that those living in Africa have little access to sufficient sun protection. In contrast, it has been suggested the mutations in the p-gene are related to melanomas[66] as well as causing oculocutaneous albinism II. Similar studies on the p-gene and skin cancer have not been done for non-melanoma cancers but it is a project which may be worth doing. It must be stated that melanomas are very infrequent in albinos of any type.[61,65–69]

Patients with vitiligo can get skin cancer of any type in their normal skin but there is a paucity of reports of non-melanoma skin cancer in the white skin.[70–81] This observation is particularly puzzling because the treatments for vitiligo include both ultraviolet B and psoralen-ultraviolet A (PUVA), both carcinogenic forms of light. Of interest is a recent report in which the incidence of skin cancer was studied in a cohort of 477 vitiligo patients.[75] Half of these were Caucasians and the other half were dark skinned (Fitzpatrick skin types IV, V, VI). There with six patients with skin cancers, all with light colored skin (Fitzpatrick types I, II, III). Four of the six occurred in normal skin and only two affected the depigmented skin. Several points are worth noting. No individuals with type IV skin or darker had a skin cancer. Depigmented skin is of the same color in individuals of all ethnic backgrounds, i.e., totally white. One would expect that the cancers affected individuals of all skin color equally. The other point is that the cancers were most common (four of the six) in the normally pigmented skin. One would expect a majority to be in the depigmented skin. This is consistent with the idea that vitiligo skin is resistant to formation of skin cancers.

It is of note that actinic damage also is less visible in white skin than in the pigmented skin of those with vitiligo [Figures 19 and 20].[60,80,82–84] Several studies on patients with vitiligo treated with PUVA showed no increase in skin cancer incidence.[70,82,85,86] In contrast, albinos exhibit sun damage from early childhood.[62,63,65] Some white skin caused by the absence of melanocytes from other causes seems susceptible to carcinogenesis. Thermal scars or depigmented skin of patients with discoid lupus are susceptible to formation of cancers. Of particular interest are patients with piebaldism caused by defects in the c-kit oncogene. As noted above, piebald skin reacts differently from normally pigmented skin to a graft versus host immune reaction.[47] In my own series of three families with piebaldism, actinic damage is common and seems to have a predilection for the white skin rather than the pigmented normal skin [Figure 21]. This seems to be the reverse of our observations for vitiligo skin. That the melanocytes have some role in inflammation, carcinogenesis and other processes seems probable.

Figure 19.

Figure 19

Open in a new tab

The neck of an African woman who had vitiligo for over 20 years. She was a farmer and worked in the sun daily. Note the elastosis of the neck, but the normal overlying white epidermis

Figure 20.

Figure 20

Open in a new tab

The hands of the African woman shown in Figure 19, who had vitiligo for over 20 years. She was a farmer and worked in the sun daily

Figure 21.

Figure 21

Open in a new tab

The arms of a woman with piebaldism (c-kit). She has marked sun damage and many actinic keratoses, mostly in the depigmented patches on her arms

There is no doubt that skin color and susceptibility to skin cancer are related. Lighter skin has a high propensity for all forms of skin cancer compared to darker skin. It has been enigmatic to me that my students from Asia, China, Korea and Japan have a skin color not that much darker than mine with a European ancestry (Swedish and Hungarian). Asians are not so pigmented as Africans, Indians or Middle Easterners. Yet, their risk for skin cancers is low. My conclusion is that skin color is just one factor related to skin cancer risk. Other factors related to repair of damage, resistance to mutation and/or other factors play as big or bigger role in defense against skin cancer as skin color. This point is made clear, especially from the data on vitiligo and albino patients and skin cancer and the types of skin cancer identified in albinos, mostly squamous cell carcinomas. Why don′t albinos get more basal cell carcinomas and/or melanomas?

Finally, it is well known among those who are interested in vitiligo that treatment is difficult and frustrating. Some of the areas of depigmentation are especially difficult to repigment, such as the hands and feet. It seems mysterious to many. However, it has been shown that the hair follicle is the reservoir for repigmentation.[87–93] Nature, for reasons not clear, evolved skin on the fingers, ventral surface of the wrist, the feet and genitalia that is hairless, i.e., glabrous. Such skin or skin with white hairs cannot respond to medical treatment [Figures 22 and 23] but only to surgical treatments which are a means to make a reservoir where there was none.

Figure 22.

Figure 22

Open in a new tab

The leg shows repigmentation from the hair follicles

Figure 23.

Figure 23

Open in a new tab

The leg has all white hairs and no repigmentation is visible except in one spot (arrows and circle)

Clearly, these are the musings of an old person thinking over the decades about vitiligo. Most of the interest by investigators is focused on an immune basis for melanocyte destruction. These studies are important to understand the cause of vitiligo. Little has been done to study the defects in the melanocytes which make them susceptible to destruction. There is so little interest in the melanocyte as a member of the inflammatory response because the prevalent bias about the melanocyte is that it is exclusively a protection against sun damage, a role it plays as part of a much larger function in the skin. There must be an important message in the fact that skin cancer is unusual in vitiligo skin but common in albino skin, the obvious difference being the presence of dysfunctional melanocytes in the latter patients. It is my hope that a younger student will not only study these phenomena and find the causes of vitiligo but also find the answer to other important questions about the epidermis and pigmentation.

Acknowledgments

I must thank first Dr. Aaron Lerner, who died just a few years ago, for stimulating my interest in vitiligo, and many other friends and colleagues with whom I have worked and collaborated with over so many years.

Footnotes

Source of Support: Nil

Conflict of Interest: Nil.

References

  • 1.Nordlund JJ, Ortonne JP. Vitiligo vulgaris. In: Nordlund JJ, Hearing VJ, King RA, Oetting W, Ortonne JP, editors. The pigmentary system: Physiology and pathophysiology. Oxford: Blackwell Scientific, Inc; 2006. pp. 591–8. [Google Scholar]
  • 2.Hann SK, Nordlund JJ, editors. 1st ed. Oxford, London: Blackwell Science Ltd; 2000. Vitiligo: A Monograph on the Basic and Clinical Science; pp. 1–386. [Google Scholar]
  • 3.Ortonne JP, Nordlund J. Mechanisms that cause abnormal skin color. In: Nordlund JJ, Boissey RE, Hearing VJ, King RA, Oetting WS, Ortonne JP, editors. The Pigmentary System: Physiology and Pathophysiology. Oxford: Blackwell Scientific Publishing; 2006. pp. 521–38. [Google Scholar]
  • 4.Nordlund JJ, Ortonne J. The normal color of human skin. In: Nordlund JJ, Boissey RE, Hearing VJ, King RA, Oetting WS, Ortonne JP, editors. The Pigmentary System: Physiology and Pathophysiology. Oxford: Blackwell Scientific; 2006. pp. 504–20. [Google Scholar]
  • 5.Boissy R, Nordlund JJ. Vitiligo: Current medical and scientific understanding. G Ital Dermatol et Venereol. 2011:46. [PubMed] [Google Scholar]
  • 6.Majumder PP, Das SK, Li CC. A genetical model for vitiligo. Am J Hum Genet. 1988;43:119–25. [PMC free article] [PubMed] [Google Scholar]
  • 7.Majumder PP, Nordlund JJ, Nath SK. Pattern of familial aggregation of vitiligo. Arch Dermatol. 1993;129:994–8. [PubMed] [Google Scholar]
  • 8.Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology of vitiligo: Multilocus recessivity cross-validated. Am J Hum Genet. 1994;55:981–90. [PMC free article] [PubMed] [Google Scholar]
  • 9.Puri N, Mojamdar M, Ramaiah A. In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects. J Investig Dermatol. 1987;88:434–8. doi: 10.1111/1523-1747.ep12469795. [DOI] [PubMed] [Google Scholar]
  • 10.Puri N, Mojamdar M, Ramaiah A. Growth defects of melanocytes in culture from vitiligo subjects are spontaneously corrected in vivo in repigmenting subjects and can be partially corrected by the addition of fibroblast-derived growth factors in vitro. Arch Dermatol Res. 1989;281:178–84. doi: 10.1007/BF00456389. [DOI] [PubMed] [Google Scholar]
  • 11.Medrano EE, Nordlund JJ. Successful culture of adult human melanocytes obtained from normal and vitiligo donors. J Investig Dermatol. 1990;95:441–5. [PubMed] [Google Scholar]
  • 12.Yang F, Sarangarajan R, Le Poole IC, Medrano EE, Boissy RE. The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity. J Invest Dermatol. 2000;114:157–64. doi: 10.1046/j.1523-1747.2000.00836.x. [DOI] [PubMed] [Google Scholar]
  • 13.Le Poole IC, Yang F, Brown TL, Cornelius J, Babcock GF, Das PK, et al. Altered gene expression in melanocytes exposed to 4-tertiary butyl phenol (4-TBP): upregulation of the A2b adenosine receptor 1. J Invest Dermatol. 1999;113:725–31. doi: 10.1046/j.1523-1747.1999.00756.x. [DOI] [PubMed] [Google Scholar]
  • 14.Nordlund J, Le Poole IC, Boissy R. Vitiligo vulgaris, in clinical and basic immunodermatology. In: Tyring AG, editor. London: Springer Verlag; 2008. pp. 661–90. [Google Scholar]
  • 15.Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol. 1996;148:1219–28. [PMC free article] [PubMed] [Google Scholar]
  • 16.Palermo B, Campanelli R, Garbelli S, Mantovani S, Lantelme E, Brazzelli V, et al. Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: The role of cellular immunity in the etiopathogenesis of vitiligo. J Invest Dermatol. 2001;117:326–32. doi: 10.1046/j.1523-1747.2001.01408.x. [DOI] [PubMed] [Google Scholar]
  • 17.Le Poole IC, Stennett LS, Bonish BK, Dee L, Robinson JK, Hernandez C, et al. Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin. Br J Dermatol. 2003;149:739–48. doi: 10.1046/j.1365-2133.2003.05539.x. [DOI] [PubMed] [Google Scholar]
  • 18.Basak PY, Adiloglu AK, Ceyhan AM, Tas T, Akkaya VB. The role of helper and regulatory T cells in the pathogenesis of vitiligo. J Am Acad Dermatol. 2009;60:256–60. doi: 10.1016/j.jaad.2008.09.048. [DOI] [PubMed] [Google Scholar]
  • 19.Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun. 2008;10:227–43. doi: 10.1159/000131485. [DOI] [PubMed] [Google Scholar]
  • 20.Huang CL, Nordlund JJ, Boissy R. Vitiligo: A manifestation of apoptosis? Am J Clin Dermatol. 2002;3:301–8. doi: 10.2165/00128071-200203050-00001. [DOI] [PubMed] [Google Scholar]
  • 21.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 Investig Dermatol. 1982;79:321–30. doi: 10.1111/1523-1747.ep12500086. [DOI] [PubMed] [Google Scholar]
  • 22.Bose SK. Probable mechanisms of loss of Merkel cells in completely depigmented skin of stable vitiligo. J Dermatol. 1994;21:725–8. doi: 10.1111/j.1346-8138.1994.tb03276.x. [DOI] [PubMed] [Google Scholar]
  • 23.Bose SK. Absence of Merkel cells in lesional skin. Int J Dermatol. 1994;33:481–3. doi: 10.1111/j.1365-4362.1994.tb02859.x. [DOI] [PubMed] [Google Scholar]
  • 24.Bose SK, Ortonne JP. Focal gaps in the basement membrane of involved and uninvolved skin of vitiligo: Are they normal? J Dermatol. 1994;21:152–9. doi: 10.1111/j.1346-8138.1994.tb01713.x. [DOI] [PubMed] [Google Scholar]
  • 25.Nordlund JJ. The epidermal melanin unit: An expanded concept. Dermatol Clin. 2007;25:271–81. doi: 10.1016/j.det.2007.04.001. [DOI] [PubMed] [Google Scholar]
  • 26.Chanco-Turner ML, Lerner AB. Physiologic changes in vitiligo. Arch Dermatolog. 1965;91:390–6. [PubMed] [Google Scholar]
  • 27.Sharquie KE, Assaf F. Sweating in vitiligo in relation to electrical skin resistance. Clin Exp Dermatol. 1985;10:598–9. doi: 10.1111/j.1365-2230.1985.tb00632.x. [DOI] [PubMed] [Google Scholar]
  • 28.Gokhale BB, Mehta LN, Damle PS. Skin resistance to electric current and its correlation with sweat gland histology in vitiligo. Indian J Med Res. 1977;66:859–64. [PubMed] [Google Scholar]
  • 29.Elwary SM, Headley K, Schallreuter KU. Calcium homeostasis influences epidermal sweating in patients with vitiligo. Br J Dermatol. 1997;137:81–5. [PubMed] [Google Scholar]
  • 30.Kumakiri M, Kimura T, Miura Y, Tagawa Y. Vitiligo with an inflammatory erythema in Vogt-Koyanagi-Harada disease: Demonstration of filamentous masses and amyloid deposits. J Cutan Pathol. 1982;9:258–66. doi: 10.1111/j.1600-0560.1982.tb01061.x. [DOI] [PubMed] [Google Scholar]
  • 31.Morohashi M, Hashimoto K, Goodman TF, Jr, Newton DE, Rist T. Ultrastructural studies of vitiligo, Vogt-Koyanagi syndrome, and incontinentia pigmenti achromians. Arch Dermatol. 1977;113:755–66. [PubMed] [Google Scholar]
  • 32.Goudie RB, Spence JC, MacKie R. Vitiligo patterns simulating autoimmune and rheumatic diseases. Lancet. 1979;2:393–5. doi: 10.1016/s0140-6736(79)90407-0. [DOI] [PubMed] [Google Scholar]
  • 33.Goudie BM, Wilkieson C, Goudie RB. A family study of vitiligo patterns. Scottish Med J. 1983;28:338–42. doi: 10.1177/003693308302800405. [DOI] [PubMed] [Google Scholar]
  • 34.Goudie RB, Soukop M, Dagg JH, Lee FD. Hypothesis: Symmetrical cutaneous lymphoma. Lancet. 1990;335:316–8. doi: 10.1016/0140-6736(90)90607-7. [DOI] [PubMed] [Google Scholar]
  • 35.Hann S. Clinical features of segmental vitiligo. In: Hann SK, Nordlund J, editors. Vitiligo: A Monograph on the Basic and Clinical Science. Oxford: Blackwell Scientific Publishers; 2000. pp. 49–60. [Google Scholar]
  • 36.Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. J Am Acad Dermatol. 1996;35:671–4. doi: 10.1016/s0190-9622(96)90718-5. [DOI] [PubMed] [Google Scholar]
  • 37.Hann SK, Chang JH, Lee HS, Kim SM. The classification of segmental vitiligo on the face. Yonsei Med J. 2000;41:209–12. doi: 10.3349/ymj.2000.41.2.209. [DOI] [PubMed] [Google Scholar]
  • 38.Hatchome N, Aiba S, Kato T, Torinuki W, Tagami H. Possible functional impairment of Langerhans′ cells in vitiliginous skin.Reduced ability to elicit dinitrochlorobenzene contact sensitivity reaction and decreased stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction. Arch Dermatol. 1987;123:51–4. doi: 10.1001/archderm.123.1.51. [DOI] [PubMed] [Google Scholar]
  • 39.Uehara M, Miyauchi H, Tanaka S. Diminished contact sensitivity response in vitiliginous skin. Arch Dermatol. 1984;120:195–8. [PubMed] [Google Scholar]
  • 40.Le Poole IC, van den Wijngaard RM, Westerhof W, Verkruisen RP, Dutrieux RP, Dingemans KP, et al. Phagocytosis by normal human melanocytes in vitro. Exp Cell Res. 1993;205:388–95. doi: 10.1006/excr.1993.1102. [DOI] [PubMed] [Google Scholar]
  • 41.Lisi P, Caraffini S. Pellagroid dermatitis from mancozeb with vitiligo. Contact Dermatitis. 1985;13:124–5. doi: 10.1111/j.1600-0536.1985.tb02520.x. [DOI] [PubMed] [Google Scholar]
  • 42.Singh KK, Srinivas CR, Balachandran C, Menon S. Parthenium dermatitis sparing vitiliginous skin. Contact Dermatitis. 1987;16:174. doi: 10.1111/j.1600-0536.1987.tb01415.x. [DOI] [PubMed] [Google Scholar]
  • 43.Srinivas CR, Singh KK, Balachandran C. Textile dermatitis sparing nevoid depigmentation. Contact Dermatitis. 1987;16:235. doi: 10.1111/j.1600-0536.1987.tb01442.x. [DOI] [PubMed] [Google Scholar]
  • 44.Lyon CC, Beck MH. Contact hypersensitivity to monobenzyl ether of hydroquinone used to treat vitiligo. Contact Dermatitis. 1998;39:132–3. doi: 10.1111/j.1600-0536.1998.tb05863.x. [DOI] [PubMed] [Google Scholar]
  • 45.Nordlund JJ, Forget B, Kirkwood J, Lerner AB. Dermatitis produced by applications of monobenzone in patients with active vitiligo. Arch Dermatol. 1985;121:1141–4. [PubMed] [Google Scholar]
  • 46.Westerhof W, Buehre Y, Pavel S, Bos JD, Das PK, Krieg SR, et al. Increased anthralin irritation response in vitiliginous skin. Arch Dermatol Res. 1989;281:52–6. doi: 10.1007/BF00424273. [DOI] [PubMed] [Google Scholar]
  • 47.Chow RK, Stewart WD, Ho VC. Graft-versus-host reaction affecting lesional skin but not normal skin in a patient with piebaldism. Br J Dermatol. 1996;134:134–7. [PubMed] [Google Scholar]
  • 48.Lerner AB, Shiohara T, Boissy RE, Jacobson KA, Lamoreux ML, Moellmann GE. A mouse model for vitiligo. J Investig Dermatol. 1986;87:299–304. doi: 10.1111/1523-1747.ep12524353. [DOI] [PubMed] [Google Scholar]
  • 49.Lamoreux ML, Boissy RE, Womack JE, Nordlund JJ. The vit gene maps to the mi (microphthalmia) locus of the laboratory mouse. J Hered. 1992;83:435–9. doi: 10.1093/oxfordjournals.jhered.a111247. [DOI] [PubMed] [Google Scholar]
  • 50.Palkowski MR, Nordlund ML, Rheins LA, Nordlund JJ. Langerhans’ cells in hair follicles of the depigmenting C57Bl/Ler-vit.vit mouse: A model for human vitiligo. Arch Dermatol. 1987;123:1022–8. [PubMed] [Google Scholar]
  • 51.Rheins LA, Palkowski MR, Nordlund JJ. Alterations in cutaneous immune reactivity to dinitrofluorobenzene in graying C57BL/vi.vi mice. J Investig Dermatol. 1986;86:539–42. doi: 10.1111/1523-1747.ep12354989. [DOI] [PubMed] [Google Scholar]
  • 52.Amornsiripanitch S, Barnes LM, Nordlund JJ, Trinkle LS, Rheins LA. Immune studies in the depigmenting C57BL/Ler-vit/vit mice: An apparent isolated loss of contact hypersensitivity. J Immunol. 1988;140:3438–45. [PubMed] [Google Scholar]
  • 53.Nordlund JJ, Csato M, Babcock G, Takei F. Low ICAM-1 expression in the epidermis of depigmenting C57BL/6J-mivit/mivit mice: A possible cause of muted contact sensitization. Exp Dermatol. 1995;4:20–9. doi: 10.1111/j.1600-0625.1995.tb00217.x. [DOI] [PubMed] [Google Scholar]
  • 54.al Badri AM, Foulis AK, Todd PM, Gariouch JJ, Gudgeon JE, Stewart DG, et al. Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo. J Pathol. 1993;169:203–6. doi: 10.1002/path.1711690205. [DOI] [PubMed] [Google Scholar]
  • 55.Norris DA. Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. J Investig Dermatol. 1990;95:111S–20S. doi: 10.1111/1523-1747.ep12874977. [DOI] [PubMed] [Google Scholar]
  • 56.Nordlund JJ, Kirkwood JM, Forget BM, Milton G, Albert DM, Lerner AB. Vitiligo in patients with metastatic melanoma: A good prognostic sign. J Am Acad Dermatol. 1983;9:689–96. doi: 10.1016/s0190-9622(83)70182-9. [DOI] [PubMed] [Google Scholar]
  • 57.Schallreuter KU, Levenig C, Berger J. Vitiligo and cutaneous melanoma: A case study. Dermatologica. 1991;183:239–45. doi: 10.1159/000247693. [DOI] [PubMed] [Google Scholar]
  • 58.Boissy R. Histology of vitiliginous skin. In: Hann SK, Nordlund J, editors. Vitiligo: Monograph on the Basic and Clinical Science. Oxford, England: Blackwell Science Ltd; 2000. pp. 23–34. [Google Scholar]
  • 59.Aquaron R. Oculocutaneous albinism in Cameroon: A 15-year follow-up study. Ophthal Paediatr Genet. 1990;11:255–63. doi: 10.3109/13816819009015711. [DOI] [PubMed] [Google Scholar]
  • 60.Calanchini-Postizzi E, Frenk E. Long-term actinic damage in sun-exposed vitiligo and normally pigmented skin. Dermatologica. 1987;174:266–71. doi: 10.1159/000249197. [DOI] [PubMed] [Google Scholar]
  • 61.Kromberg JG, Castle D, Zwane EM, Jenkins T. Albinism and skin cancer in Southern Africa. Clin Genet. 1989;36:43–52. doi: 10.1111/j.1399-0004.1989.tb03365.x. [DOI] [PubMed] [Google Scholar]
  • 62.Lookingbill D, Lookingbill G, Leppard B. Actinic lentigines versus skin cancer risk in albinos in northern Tanzania. J Am Acad Dermatol. 1995;33:299–300. doi: 10.1016/0190-9622(95)90264-3. [DOI] [PubMed] [Google Scholar]
  • 63.Lookingbill D, Lookingbill GL, Leppard B. Actinic damage and skin cancer in albinos in northern Tanzania: Finding in 164 patients enrolled in an outreach skin care program. J Am Acad Dermatol. 1995;32:653–8. doi: 10.1016/0190-9622(95)90352-6. [DOI] [PubMed] [Google Scholar]
  • 64.Oettle AG. Skin Cancer in Africa. NCI Monogr. No. 10. 1963;10:197–214. [Google Scholar]
  • 65.Yakubu A, Mabogunje OA. Skin cancer in African albinos. Acta Oncol. 1993;32:621–2. doi: 10.3109/02841869309092440. [DOI] [PubMed] [Google Scholar]
  • 66.Jannot AS, Meziani R, Bertrand G, Gérard B, Descamps V, Archimbaud A, et al. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur J Hum Genet. 2005;13:913–20. doi: 10.1038/sj.ejhg.5201415. [DOI] [PubMed] [Google Scholar]
  • 67.Luande J, Henschke CI, Mohammed N. The Tanzanian human albino skin. Nat Hist Cancer. 1985;55:1823–8. doi: 10.1002/1097-0142(19850415)55:8<1823::aid-cncr2820550830>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  • 68.Streutker CJ, McCready D, Jimbow K, From L. Malignant melanoma in a patient with oculocutaneous albinism. J Cutan Med Surg. 2000;4:149–52. doi: 10.1177/120347540000400307. [DOI] [PubMed] [Google Scholar]
  • 69.Pehamberger H, Honigsmann H, Wolff K. Dysplastic nevus syndrome with multiple primary amelanotic melanomas in oculocutaneous albinism. J Am Acad Dermatol. 1984;11:731–5. doi: 10.1016/s0190-9622(84)70230-1. [DOI] [PubMed] [Google Scholar]
  • 70.Wildfang IL, Jacobsen FK, Thestrup-Pedersen K. PUVA treatment of vitiligo: A retrospective study of 59 patients. Acta Dermato-Venereol. 1992;72:305–6. [PubMed] [Google Scholar]
  • 71.Seo SL, Kim IH. Squamous cell carcinoma in a patient with generalized vitiligo. J Am Acad Dermatol. 2001;45:S227–9. doi: 10.1067/mjd.2001.103990. [DOI] [PubMed] [Google Scholar]
  • 72.Hannuksela-Svahn A, Sigurgeirsson B, Pukkala E, Lindelöf B, Berne B, Hannuksela M, et al. Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis. Br J Dermatol. 1999;141:497–501. doi: 10.1046/j.1365-2133.1999.03044.x. [DOI] [PubMed] [Google Scholar]
  • 73.Park HS, Lee YS, Chun DK. Squamous cell carcinoma in vitiligo lesion after long-term PUVA therapy. J Eur Acad Dermatol Venereol. 2003;17:578–80. doi: 10.1046/j.1468-3083.2003.00815.x. [DOI] [PubMed] [Google Scholar]
  • 74.Brazzelli V, Barbagallo T, Prestinari F, Vassallo C, Agozzino M, Vailati F, et al. Keratoacanthoma in vitiligo lesion after UVB narrowband phototherapy. Photodermatol Photoimmunol Photomed. 2006;22:211–3. doi: 10.1111/j.1600-0781.2006.00224.x. [DOI] [PubMed] [Google Scholar]
  • 75.Hexsel CL, Eide MJ, Johnson CC, Krajenta R, Jacobsen G, Hamzavi I, et al. Incidence of nonmelanoma skin cancer in a cohort of patients with vitiligo. J Am Acad Dermatol. 2009;60:929–33. doi: 10.1016/j.jaad.2008.09.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Arnon O, Mamelak AJ, Goldberg LH. Basal cell carcinoma arising in a patient with vitiligo. J Drugs Dermatol. 2008;7:1075–6. [PubMed] [Google Scholar]
  • 77.Attili S, Attili VR. Keratoacanthoma centrifugum marginatum arising in vitiligo: A case report. Dermatol Online J. 2006;12:18. [PubMed] [Google Scholar]
  • 78.Halder RM, Battle EF, Smith EM. Cutaneous malignancies in patients treated with psoralen photochemotherapy (PUVA) for vitiligo. Arch Dermatol. 1995;131:734–5. [PubMed] [Google Scholar]
  • 79.Akimoto S, Suzuki Y, Ishikawa O. Multiple actinic keratoses and squamous cell carcinomas on the sun-exposed areas of widespread vitiligo. Br J Dermatol. 2000;142:824–5. doi: 10.1046/j.1365-2133.2000.03440.x. [DOI] [PubMed] [Google Scholar]
  • 80.Saarinen K, Lestringant GG, Masouye I, Frossard PM. Actinic damage and squamous cell carcinoma in sun-exposed skin affected by vitiligo. Br J Dermatol. 2000;143:219–21. doi: 10.1046/j.1365-2133.2000.03636.x. [DOI] [PubMed] [Google Scholar]
  • 81.Takeda H, Mitsuhashi Y, Kondo S. Multiple squamous cell carcinomas in situ in vitiligo lesions after long-term PUVA therapy. J Am Acad Dermatol. 1998;38:268–70. doi: 10.1016/s0190-9622(98)70247-6. [DOI] [PubMed] [Google Scholar]
  • 82.Harrist TJ, Pathak MA, Mosher DB, Fitzpatrick TB. Chronic cutaneous effects of long-term psoralen and ultraviolet radiation therapy in patients with vitiligo. Nat Cancer Inst Monogr. 1984;66:191–6. [PubMed] [Google Scholar]
  • 83.Yashiro K, Nakagawa T, Takaiwa T, Inai M. Actinic keratoses arising only on sun-exposed vitiligo skin. Clin Exp Dermatol. 1999;24:199–201. doi: 10.1046/j.1365-2230.1999.00454.x. [DOI] [PubMed] [Google Scholar]
  • 84.Schallreuter KU, Tobin DJ, Panske A. Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo. Dermatology. 2002;204:194–201. doi: 10.1159/000057881. [DOI] [PubMed] [Google Scholar]
  • 85.Abdullah AN, Keczkes K. Cutaneous and ocular side-effects of PUVA photochemotherapy--a 10-year follow-up study. Clin Exp Dermatol. 1989;14:421–4. doi: 10.1111/j.1365-2230.1989.tb02602.x. [DOI] [PubMed] [Google Scholar]
  • 86.Buckley DA, Rogers S. Multiple keratoses and squamous carcinoma after PUVA treatment of vitiligo. Clin Exp Dermatol. 1996;21:43–5. [PubMed] [Google Scholar]
  • 87.Arrunategui A, Arroyo C, Garcia L, Covelli C, Escobar C, Carrascal E, et al. Melanocyte reservoir in vitiligo. Int J Dermatol. 1994;33:484–7. doi: 10.1111/j.1365-4362.1994.tb02860.x. [DOI] [PubMed] [Google Scholar]
  • 88.Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Investig Dermatol. 1991;97:410–6. doi: 10.1111/1523-1747.ep12480997. [DOI] [PubMed] [Google Scholar]
  • 89.Dourmishev AL. On the mechanism of perifollicular repigmentation in vitiligo. Doklady Bolgarskoi Academii Navk. 1982;35:789–91. [Google Scholar]
  • 90.Ortonne JP, MacDonald DM, Micoud A, Thivolet J. Repigmentation of vitiligo induced by oral photochemotherapy.Histoenzymological and ultrastructural study (Article in French) Ann Dermatol Venereol. 1978;105:939–40. [PubMed] [Google Scholar]
  • 91.Ortonne JP, MacDonald DM, Micoud A, Thivolet J. PUVA-induced repigmentation of vitiligo: A histochemical (split-DOPA) and ultrastructural study. Br J Dermatol. 1979;101:1–12. doi: 10.1111/j.1365-2133.1979.tb15285.x. [DOI] [PubMed] [Google Scholar]
  • 92.Ortonne JP, Schmitt D, Thivolet J. PUVA-induced repigmentation of vitiligo: Scanning electron microscopy of hair follicles. J Investig Dermatol. 1980;74:40–2. doi: 10.1111/1523-1747.ep12514597. [DOI] [PubMed] [Google Scholar]
  • 93.Cui J. The melanocyte reservoir and its necessity. In: Hann SK, Nordlund J, editors. Vitiligo: Monograph on Basic and Clinical Science. Oxford, England: Blackwell Science Ltd; 2000. pp. 163–5. [Google Scholar]

Articles from Indian Journal of Dermatology are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES