Vitiligo

Background

Vitiligo is the depigmentation of the skin caused by loss of the melanocytes. It gained noteriety in the 1980's when entertainer Michael Jackson was reported to be afflicted with this condition.

OUTLINE

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

DISEASE ASSOCIATIONS CHARACTERIZATION

BONE MARROW TRANSPLANTATION

Transfer of vitiligo after allogeneic bone marrow transplantation.

Alajlan A, Alfadley A, Pedersen KT.

Department of Medicine, King Faisal Specialist Hospital and Research Centre.

J Am Acad Dermatol 2002 Apr;46(4):606-10 Abstract quote
Adoptive transfer of donor immunity has been demonstrated in animals after bone marrow transplantation (BMT). In humans, several autoimmune diseases have been similarly transferred. Although BMT may, per se, be associated with a modulation of the recipient's immune system, which could trigger or even cause autoimmune diseases, both animal experiments and experience with humans show the likeliness of adoptive transfer of donor immunity to the recipient.

We describe a patient with multiple myeloma in whom generalized vitiligo developed within 3 months after allogeneic BMT from his HLA-matched sister with vitiligo. We believe that a form of adoptive transfer of donor immunity to the recipient might play a role in the development of vitiligo. In spite of this, neither de novo development of vitiligo in a genetically predisposed patient nor autoimmune phenomena associated with graft-versus-host disease can be completely excluded as a contributing factor for development of vitiligo in our patient.

To our knowledge, this is the first case report of transfer of vitiligo after BMT from a donor with vitiligo.

IDIOPATHIC CD4+ T-CELL LYMPHOCYTOPENIA

Idiopathic CD4+T-cell lymphocytopenia associated with vitiligo.

Yamauchi PS, Nguyen NQ, Grimes PE.

Division of Dermatology, University of California Los Angeles School of Medicine, and the Vitiligo and Pigmentation Institute of Southern California.

J Am Acad Dermatol 2002 May;46(5 Pt 1):779-82 Abstract quote
The syndrome of idiopathic CD4(+) T lymphocytopenia (ICTL) is defined as the persistent depletion of peripheral blood CD4(+) T lymphocytes below 300 cells/mm(3) or less than 20% of the total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency.

To date no known viral origin has been identified. ICTL has a variable clinical course ranging from patients with minimal symptoms to those who have died from opportunistic infections. We report a case of a 32-year-old white man with a long history of vitiligo that is associated with ICTL. He also had incidental psoriasis.

The correlation between ICTL and autoimmune vitiligo suggests an aberration in the immune surveillance that leads to an abnormal response of CD4(+) T lymphocytes in the host.

VOGT-KOYANAGI-HARADA DISEASE

J Am Acad Dermatol 2001;44:129-131

Inflammatory vitiligo with thin raised erythema around depigmented areas

SQUAMOUS CELL CARCINOMA

Squamous cell carcinoma in a patient with generalized vitiligo

Seung-Lee Seo, MD
Il-Hwan Kim, MD,PhD

Seoul, Korea

J Am Acad Dermatol 2001;45:S227-9 Abstract quote

Association of vitiligo and skin cancer has been a subject of controversy. Occurrence of skin cancer in long-lasting vitiligo is rare, and PUVA therapy-associated squamous cell carcinomas are not reported until recent years.

We report a case of squamous cell carcinoma and actinic keratosis in long-lasting vitiliginous patches in a patient with generalized vitiligo who did not receive PUVA therapy.

Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo.

Schallreuter KU, Tobin DJ, Panske A.

Institute for Pigmentary Disorders, Greifswald, Germany.
Dermatology 2002;204(3):194-201 Abstract quote
Background: It is well established that ultraviolet radiation is related to non-melanoma skin cancer (NMSC) in Caucasians. Considering that patients with vitiligo have often no protective pigment in sun-exposed depigmented/white skin together with severe oxidative stress due to accumulation of millimolar epidermal hydrogen peroxide (H(2)O(2)), it would be expected that these patients develop a higher risk for early photodamage and NMSC. However, scattered reports on low patient numbers documented no increased risk for sun-induced skin cancers in this disease.

Objective: The aim of this study was to validate the possible photodamage and the development of epidermal neoplasia in a randomly selected larger patient group with emphasis on each patient's sun sensitivity and the history of solar habits. Furthermore we wished to compare histological signs for epidermal photodamage in a random representative patient group (mean age >30 years) and age-matched healthy controls.

Methods: One hundred and thirty-six randomly selected patients (females n = 93; males n = 43; mean age 42.4 years, range 14-70 years) were included in this study. To assess signs of photodamage and skin cancer, all patients underwent a thorough full-body examination by Wood's light and dermatoscopy. In order to learn about each patient's individual sun sensitivity and solar habits, a direct questionnaire was used. In addition full skin punch biopsies of sun-exposed depigmented/pigmented skin were taken under local anaesthesia and evaluated by light microscopy.

Results: There was no evidence for sun-related damage in the entire patient group, despite a significant number of positive cases with a history of sunburns in early childhood and continuous accumulation of epidermal H(2)O(2). Histological examination of the epidermis showed no signs of increased photo-ageing and confirmed the absence of apoptosis in these patients. Furthermore surprisingly there was no increased risk for photosensitivity disorders, i.e. polymorphous light reaction, solar urticaria and acute actinic dermatitis.

Conclusion: The results of this study confirm in a large group of patients with vitiligo the absence of an expected high risk for sun-induced damage and skin cancer. Based on these results together with a recent report on increased functional wild-type p53 expression in these patients we would like to propose that in vitiligo there may be a direct association between this important tumour suppressor and the absence of photodamage and NMSC.

PATHOGENESIS CHARACTERIZATION

GENERAL

Characteristics of genetic epidemiology and genetic models for vitiligo.

Zhang XJ, Liu JB, Gui JP, Li M, Xiong QG, Wu HB, Li JX, Yang S, Wang HY, Gao M, Yang J, Yang Q.

Institute of Dermatology, Anhui Medical University, Hefei, China.

J Am Acad Dermatol. 2004 Sep;51(3):383-90. Abstract quote

BACKGROUND: Vitiligo occurs with a frequency of 0.1% to 2% in various populations and is classified into several subtypes by its clinical presentation. Although genetic factors are thought to be involved in the cause of vitiligo, the genetic models for different phenotypes of vitiligo are unknown.

OBJECTIVE: Our purpose was to explore potential genetic models for different phenotypes of vitiligo and analyze genetic epidemiologic characteristics of vitiligo in a Chinese population.

METHODS: Information from 2247 patients and members in their families was collected using a uniform questionnaire. Patients' clinical characteristics and their family history were analyzed using software. A complex segregation analysis was conducted to propose potential genetic models for vitiligo.

RESULTS: Different subtypes of vitiligo had different ages of disease onset. In relatives of patients with vitiligo, the risk of developing vitiligo increased with increasing relatedness to the patients with vitiligo. A polygenic additive model was the best model for focal vitiligo, vitiligo vulgaris, acrofacial vitiligo, and segmental vitiligo with approximately 50% heritability in each. For universal vitiligo, the best model was an environmental model.

CONCLUSION: This study indicated that different phenotypes of vitiligo had different pathogeneses and genetic backgrounds. Onset of vitiligo is possibly affected by both genetic backgrounds and common environmental factors.

Inflammatory changes in vitiligo: stage I and II depigmentation.

Sharquie KE, Mehenna SH, Naji AA, Al-Azzawi H.

Department of Dermatology, College of Medicine, Baghdad University, P.O. Box 61080, Postal Code Number 12114, Medical Collection Post Office, Baghdad, Iraq

Am J Dermatopathol. 2004 Apr;26(2):108-12. Abstract quote

Frequent failure of early studies to demonstrate inflammatory changes in vitiligo led many investigators to consider the disease as noninflammatory. However, others found an inflammatory element in vitiliginous lesions.

In this study we tried to verify that assumption. Twenty-five patients (10 males and 15 females) with common vitiligo and 11 normal healthy individuals were included. Histopathologic studies were carried out using epon-embedded sections stained with modified toluidine blue stain. Comparisons of the results of histopathologic examination of the stained specimens of vitiliginous lesions (both stage I and II), marginal areas, and uninvolved normal skin of vitiligo patients with normal healthy control were performed. Focal spongiosis was observed in 48% of the specimens of vitiligo patients and largely limited to the marginal areas and stage I vitiligo lesions. Epidermal mononuclear cell infiltration was seen in 80% of both the marginal areas and stage I vitiligo specimens. The number of these cells was significantly higher than that in stage II lesions and uninvolved skin. Many of the epidermotropic lymphocytes were grouped together, forming clusters resembling Pautrier microabscesses. The extent of epidermal mononuclear cell invasion did not always parallel the density of the subjacent dermal infiltrate.

Vitiligo is an inflammatory disease, and the epidermal lymphocytic infiltration is most likely the primary immunologic event.

VITAMIN D

A pilot study assessing the role of 25 hydroxy vitamin D levels in patients with vitiligo vulgaris.
Silverberg JI, Silverberg AI, Malka E, Silverberg NB.

Department of Pathology, Center for Allergy and Asthma Research, SUNY, and Downstate Medical Center, Brooklyn, New York, USA.

J Am Acad Dermatol. 2010 Jun;62(6):937-41. Abstract
BACKGROUND: Very low vitamin D levels have been noted in patients with a variety of autoimmune diseases.

OBJECTIVE: To determine whether low vitamin D levels are associated with autoimmunity in the setting of vitiligo vulgaris.

METHODS: A prospective cohort study was conducted on 45 consecutive patients with vitiligo vulgaris. 25-Hydroxyvitamin D levels were determined from sera collected at the time of study enrollment. Logistic regression analysis of the relationship of 25-hydroxyvitamin D levels to disease state was performed, including surface area, recent-onset vitiligo, Fitzpatrick skin type and ethnicity, dairy intake, and both personal and family history of autoimmunity. Multiple univariate and multivariate logistic regression models were developed to assess the interrelationship of these parameters.

RESULTS: 25-Hydroxyvitamin D levels were divided into 3 groups: 31.1% were normal (>30 ng/mL), 55.6% were insufficient (<30 ng/mL), and 13.3% were very low (<15 ng/mL). Insufficient 25-hydroxyvitamin D levels were associated with increasing Fitzpatrick phototypes (odds ratio [OR] = 1.76, 95% confidence interval [CI] = 1.12-2.77). Very low 25-hydroxyvitamin D levels were associated with comorbid autoimmune illness (OR = 10.00, 95% CI = 1.06-94.7), but not with age, gender, race/ethnicity, family history of vitiligo or autoimmune disease, new-onset disease, or body surface area affected. None of the surveyed patients reported daily vitamin D intake of greater than 200 IU.

LIMITATIONS: This study consists of a small cohort that assesses point prevalence without assessing seasonal variation in vitamin D levels.

CONCLUSIONS: Very low 25-hydroxyvitamin D levels (<15 ng/mL) appear to be a reasonable screening tool for the presence of comorbid autoimmunity. Furthermore, we demonstrate that Fitzpatrick phototype, rather than ethnicity, is specifically associated with 25-hydroxyvitamin D levels that are insufficient (<30 ng/mL).

HISTO-PATHOLOGICAL VARIANTS CHARACTERIZATION

GENERAL

Histopathologic features in vitiligo.

Kim YC, Kim YJ, Kang HY, Sohn S, Lee ES.

Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.

Am J Dermatopathol. 2008 Apr;30(2):112-6. Abstract quote

Nevus depigmentosus is a congenital disorder characterized by a nonprogressive hypopigmented lesion, which may not be apparent at birth. Thus, it is sometimes difficult to differentiate vitiligo from nevus depigmentosus only by clinical features. We postulated that the histologic changes in lesional and perilesional skin might be different in the 2 conditions.

We took biopsies from both lesional and perilesional skin of 100 cases of vitiligo to assess the number of melanocytes, the amount of melanin, dermal inflammatory infiltrate, and other changes. We compared them with 30 cases of nevus depigmentosus. Histologically, lesions of vitiligo showed more basal hypopigmentation and dermal inflammation than perilesional normal skin. With Fontana-Masson staining, 16% of cases of vitiligo showed the presence of melanin. The ratio of pigmented area to epidermal area was 0.06% in vitiligo, whereas 17% in perilesional normal skin and 8.9% in nevus depigmentosus. In NKI/beteb staining, 12% of vitiligo showed the presence of melanocytes, and their average number was 7.68 per square millimeter. The number of melanocytes was also decreased in nevus depigmentosus but not as much as in vitiligo. We also confirmed the presence of melanocytes in 1 of 3 cases of vitiligo by electron microscopy.

In conclusion, there are a few melanocytes and melanin in some cases of vitiligo. Therefore, the diagnosis of vitiligo should be made considering these points.

Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation.

Le Poole IC, van den Wijngaard RM, Westerhof W, Dutrieux RP, Das PK.

Department of Dermatology, Amsterdam University, The Netherlands.

J Invest Dermatol 1993 Jun;100(6):816-22 Abstract quote
There is a long-standing controversy over whether melanocytes in vitiligo lesions are actually lost or are still present but inactivated. Resolving this matter is essential for understanding the underlying pathology and for the development of treatment. Standard methods of detecting melanocytes are based on active melanin synthesis. However, it is possible that inactive melanocytes remain in the lesions. There are no methods presently available to detect such dormant melanocytes.

Using a panel of one polyclonal and 17 monoclonal antibodies directed against melanocytic cells (largely selected by the European Organisation for Research and Treatment of Cancer Melanoma Group for diagnostic and therapeutic purposes), we investigated the absence or inactivation of melanocytes in vitiligo by immunohistochemistry. Results using this panel of antibodies on frozen skin sections suggest that melanocytes are indeed absent in the lesions. However, in epidermal split-skin preparations, residual staining was occasionally observed. To determine whether the staining obtained was due to degenerated melanocytes, confocal laser scanning microscopy was used. Immunofluorescent staining using the antibody NKI-beteb confirmed this to be the case.

The results presented here strongly suggest that melanocytes are indeed lost in vitiligo lesions.

Melanocytes are not absent in lesional skin of long duration vitiligo.

Tobin DJ, Swanson NN, Pittelkow MR, Peters EM, Schallreuter KU.

Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, UK.
J Pathol 2000 Aug;191(4):407-16 Abstract quote
This paper provides evidence that melanocytes are still present in the depigmented epidermis of patients with vitiligo even after stable disease of 25 years' duration. Melanocyte cultures were successfully established from depigmented epidermal suction blister tissue of all 12 randomly selected patients and these cells produced melanin. Even under in vitro conditions, vacuolation of melanocytes was demonstrated in five patients with active disease, which was reversible upon exogenous addition of bovine catalase to the culture medium.

Full skin biopsies from 17 patients with vitiligo, obtained from depigmented and normally pigmented areas, confirmed the involvement of melanocytes, keratinocytes, and Langerhans cells in this disorder. In addition, the presence of clustered and single pre-melanosomes in basal and supra-basal keratinocytes of lesional and normal epidermis, as well as the retention of single melanocytes in lesional epidermis, was demonstrated by light and electron microscopy. Upon topical application of a narrow band UVB-activated pseudocatalase, vacuolation, granulation, and dilatation of the endoplasmic reticulum completely recovered, but the ectopic pre-melanosome shedding remained.

Taken together, these observations indicate that melanocytes are never completely absent in the depigmented epidermis and that these melanocytes can recover their functionality in vivo and in vitro upon the removal of hydrogen peroxide. Furthermore, this study supports the concept that vitiligo involves the entire epidermal unit in both depigmented and 'normal' pigmented skin.

VARIANTS

TRICHOME VITILIGO

Clinical and histopathologic characteristics of trichrome vitiligo.

Hann SK, Kim YS, Yoo JH, Chun YS.

Department of Dermatology, Yonsei University College of Medicine, and the Pochon CHA Medical College, Pundang CHA Hospital.
J Am Acad Dermatol 2000 Apr;42(4):589-96 Abstract quote
BACKGROUND: The term trichrome vitiligo describes lesions that have a tan zone of varying width between normal and totally depigmented skin, which exhibits an intermediate hue. However, the pathogenesis and the histopathologic characteristics of trichrome vitiligo are unknown.

OBJECTIVE: Our purpose was to investigate the clinical and histopathologic characteristics and the pathogenesis of trichrome vitiligo.

METHODS: Four punch biopsy specimens were taken from 21 patients with trichrome vitiligo; they were from vitiliginous skin, light brown skin, perilesional normal skin, and normal skin as far as 5 cm from the nearest vitiligo spot. The sections were stained with hematoxylin-eosin; in selected cases, we performed immunohistochemical staining with S-100 protein and CD1a.

RESULTS: Trichrome vitiligo occurred most frequently on the trunk in active vitiligo vulgaris. Focal vacuolar degeneration of the basal cell layer and mild inflammatory cell infiltration of the epidermis and dermis were more prominent in light brown skin and perilesional normal skin than in vitiliginous skin and normal skin. The number of melanocytes was decreased in light brown skin compared with perilesional normal skin (P <.05) and in vitiliginous skin compared with light brown skin (P <.05); a few melanocytes were observed even in skin affected by trichrome vitiligo. The number of Langerhans cells was increased in the epidermis of light brown skin and perilesional normal skin compared with vitiliginous and normal skin (P <.05). PUVA therapy yielded excellent repigmentation.

CONCLUSION: Trichrome vitiligo is a variant of active vitiligo. The changes of melanocytes, keratinocytes, and Langerhans cells may be involved in the pathogenesis of depigmentation in trichrome vitiligo.

SPECIAL STAINS/
IMMUNOPEROXIDASE
CHARACTERIZATION

ELECTRON MICROSCOPE

Ultrastructural studies in stable vitiligo.

Panuncio AL, Vignale R.

Am J Dermatopathol 2003 Feb;25(1):16-20 Abstract quote
Vitiligo is a disease of melanocytes characterized by achromic lesions in the skin, affecting the epidermis and the pilosebaceous follicle.

We performed an ultrastructural analysis of biopsy specimens from four patients with noninflammatory, stable vitiligo of long duration (three had generalized vitiligo and one had segmental vitiligo). The samples were taken from the oldest achromic lesions, and the biopsy sites were far from normal skin. In all cases we noted alterations in keratinocytes, Langerhans cells, and melanocytes. We also found lymphocytes in the epidermis, and these cells and macrophages were noted in the dermis. The basal membrane disappeared at some points, and sometimes it was possible to see dermal cells with processes that engulfed either granular material or vesicles of epidermal origin in such areas.

Our studies suggest that even in stable vitiligo, achromia implies intense cytologic activity, probably involving cell-mediated cytotoxicity, and ultrastructural findings resemble those of a lichenoid reaction.

DIFFERENTIAL DIAGNOSIS CHARACTERIZATION

NEVUS DEPIGMENTOSUS

Clinical and histopathologic characteristics of nevus depigmentosus.

Kim SK,
Kang HY,
Lee ES,
Kim YC.

Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.

J Am Acad Dermatol. 2006 Sep;55(3):423-8. Abstract quote

BACKGROUND: Nevus depigmentosus (ND) is known to be a rare congenital, nonprogressive disorder characterized by a hypopigmented lesion that remains stable over time. There have been only few studies of clinical and histopathologic characteristics of ND, and the etiopathogenesis is not fully established.

OBJECTIVE: The purpose of this study was to investigate the clinical and histopathologic characteristics of ND.

METHODS: A clinical survey was carried out with 60 patients given the diagnosis of ND. Punch biopsies (2 mm) from lesional and perilesional normal skin were performed. The sections were stained with hematoxylin-eosin, Fontana-Masson, antibodies to S-100 protein, MART-1, NKI/beteb, CD1a, CD3, CD20, and CD68.

RESULTS: The lesions were usually present before the age of 3 years (68.3%), but some lesions appeared later in childhood (31.7%). In all, 27 patients (45%) had one lesion, but there were 14 patients (23.3%) who had more than 10 lesions. Fontana-Masson stain showed that the amount of melanin was significantly decreased in ND skin compared with perilesional normal skin. Melanocyte counts were significantly decreased in ND skin when stained with antibodies to GP-100 and MART-1. However, there were no significant differences in the number of melanocytes identified as S-100 protein-positive cells. There were no significant differences in histologic findings or dermal inflammatory infiltrates between ND skin and perilesional normal skin.

LIMITATIONS: Only 29 patients (48.3%) were followed up, and the average follow-up period after initial diagnosis was relatively short (68 months); therefore, these overall results may not be representative of the clinical course of the patients.

CONCLUSION: Only 18 patients (30.0%) presented with ND since birth and only 27 patients (45.0%) had one lesion. Both the amount of melanin and the number of melanocytes in ND skin were decreased in patients with ND. Therefore, both clinical and histologic findings should be considered together to make a diagnosis of ND.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSIS

TREATMENT

ALLOGRAFTS

Long-term Follow-up Study of Segmental and Focal Vitiligo Treated by Autologous, Noncultured Melanocyte-Keratinocyte Cell Transplantation
Sanjeev V. Mulekar, MD

Arch Dermatol 2004;140:1211-1215 Abstract quote
Objective To evaluate long-term efficacy and safety of melanocyte-keratinocyte cell transplantation in the management of segmental and focal vitiligo.
Design A simpler and modified method based on that of Olsson and Juhlin was performed. This method uses a shaved biopsy skin sample up to one tenth the size of the recipient area. The skin sample is incubated, and the cells are mechanically separated using trypsin-EDTA solution and then centrifuged to prepare a suspension. Cell suspension is then applied to the dermabraded depigmented skin area, and a collagen dressing is applied to keep it in place.
Patients Fifty patients with segmental and 17 with focal vitiligo were treated. One patient with segmental and 2 with focal vitiligo did not attend any follow-up visits. The remaining patients were observed for a period of up to 5 years.
Intervention Autologous, noncultured melanocyte-keratinocyte cell transplantation.
Main Outcome Measure Repigmentation was graded as excellent with 95% to 100% pigmentation, good with 65% to 94%, fair with 25% to 64%, and poor with 0% to 24% of the treated area.
Results In the segmental vitiligo group, 41 patients (84%) showed excellent, 3 (6%) good, and 5 (10%) poor pigmentation, which was retained until the end of the respective follow-up period. In the focal vitiligo group, 11 patients (73%) showed excellent, 1 (7%) fair, and 3 (20%) poor pigmentation, which was retained until the end of the respective follow-up period.
Conclusions Melanocyte-keratinocyte cell transplantation is a simple, safe, and effective surgical therapy. Patients with segmental and focal vitiligo can experience a prolonged disease-free period, which may extend through the rest of their lives.

Double-blind Placebo-Controlled Study of Autologous Transplanted Epidermal Cell Suspensions for Repigmenting Vitiligo
Nanny van Geel, MD; Katia Ongenae, MD; Martine De Mil; Yves Vander
Haeghen, PhD; Chris Vervaet, PhD; Jean Marie Naeyaert,
MD, PhD
Arch Dermatol. 2004;140:1203-1208. Abstract quote

Objectives To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory, spontaneous, or UV-induced pigmentation in obtaining repigmentation.
Design A prospective, randomized, double-blind, placebo-controlled study. Setting Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months. Patients A total of 33 paired, symmetrically distributed leukodermic lesions, all resistant to therapy, were observed in 28 patients. Nineteen patients appeared to have a stable vitiligo (group 1), whereas there was doubt about the stability of the disease in 9 patients (group 2). Intervention After laser ablation, a hyaluronic acid–enriched cellular graft was applied to 1 lesion while the paired lesion received placebo. Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months. Main Outcome Measures Primarily, the percentage of repigmentation was assessed after 3, 6, and 12 months using a digital image analysis system. The repigmentation pattern was also evaluated after 1 and 3 months.
Results A strongly significant difference between cellular grafts and placebo was observed after 3, 6, and 12 months (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively treated lesions 3, 6, and 12 months after treatment, whereas in group 2 repigmentation of at least 70% of the treated area was not observed at any time point. The repigmentation pattern was diffuse in 94% of the responding patients.
Conclusions After a strict preoperative selection for disease stability, transplantation resulted in repigmentation of at least 70% of the treated area in most actively treated vitiligo lesions. Repigmentation was primarily caused by the transplanted melanocytes.

Epidermal grafting in vitiligo: influence of age, site of lesion, and type of disease on outcome.

Gupta S, Kumar B.

Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Am Acad Dermatol. 2003 Jul;49(1):99-104. Abstract quote
BACKGROUND: The success of suction blister epidermal grafting may be influenced by various factors, all of which have not been studied to date.

OBJECTIVE: We sought to determine the influence of age of the patient, site of vitiligo patch, and type of disease on the outcome of the procedure in our patients and in the cumulative data derived from literature analysis.

METHODS: This was a retrospective, uncontrolled case series and literature review of suction blister epidermal grafting in patients with stable and recalcitrant vitiligo. All published studies of suction blister epidermal grafting in vitiligo involving 10 or more patients were included in the literature analysis.

RESULTS: The procedure was performed in 143 patients. However, sufficient length (6 postoperative months) of follow-up was available in only 117 patients, and only these patients were included for analysis. Only limited information was available about various factors in the majority of published studies. The success rates for generalized and segmental/focal disease in this study were 53% (confidence interval [CI] 42-64) and 91% (CI 81-100), respectively (P <.001), and in the literature, 61% (CI 46-76) and 88% (CI 82-94), respectively (P <.01). The success rates in patients aged < 20 years and >or= 20 years in this study were 82% (CI 67-97) and 58% (CI 48-68), respectively (P <.05), and in the literature, 100% and 66% (CI 56-76), respectively (P <.05). There was no significant difference in the success rates achieved on different body sites in this study and in the screened literature. Among adverse reactions, hyperpigmentation in 32% (CI 24-40) and 17% (CI 14-20), infection in 6% (CI 2-10) and 0%, and contact dermatitis in 1% (CI 0-3) and 1% (CI 0-2) of patients were observed in this study and in the analyzed literature, respectively.

CONCLUSIONS: The results were significantly better in segmental/focal vitiligo than in the generalized type, and in individuals < 20 years of age. However, unlike in medical therapies, localization of the vitiligo patch did not influence the treatment outcome significantly.

Autologous grafting with noncultured melanocytes: a simplified method for treatment of depigmented lesions.

Gauthier Y, Surleve-Bazeille JE.

Dermatology Service, Hopital Pellegrin, Bordeaux, France.
J Am Acad Dermatol 1992 Feb;26(2 Pt 1):191-4 Abstract quote
BACKGROUND: Achromic lesions on the trunk and the extremities often do not respond to treatment and little improvement is obtained in cases of segmental vitiligo.

OBJECTIVE: Transplantation of autologous noncultured melanocytes was performed to obtain a successful repigmentation.

METHODS: The grafting method is carried out in two steps: production of blisters on the depigmented lesions by freezing with liquid nitrogen and injection in each blister of a suspension of epidermal cells (mainly keratinocytes and melanocytes). The cellular suspension was obtained from samples of skin of the hair scalp after trypsinization.

RESULTS: Repigmentation was evident within 25 to 30 days. Coalescence of the pigmented areas was spontaneously observed or obtained after UVA stimulation. Patients with two types of leukoderma-vitiligo or nevus depigmentosus had successful repigmentation after transplantation of autologous noncultured melanocytes.

CONCLUSION: This technique appears to be an effective and simple method for treating patients with achromic areas lacking melanocytes.

Modified technique of autologous noncultured epidermal cell transplantation for repigmenting vitiligo: a pilot study.

van Geel N, Ongenae K, De Mil M, Naeyaert JM.

Department of Dermatology, Ghent University Hospital, Ghent, Belgium.
Dermatol Surg 2001 Oct;27(10):873-6 Abstract quote
BACKGROUND: Several reports have demonstrated that grafting of autologous melanocytes from normally pigmented donor skin can be used for repigmentation of achromic macules in vitiligo.

OBJECTIVE: To investigate a modified approach in which noncultured autologous melanocytes and keratinocytes are grafted on superficially laser dermabraded vitiligo lesions in a suspension enriched with hyaluronic acid.

METHODS: Four patients with stable vitiligo were treated using a noncultured melanocyte-keratinocyte suspension. The cellular suspension was grafted on vitiliginous lesions previously dermabraded with a CO2 laser. To improve the viscosity and fixation of the cellular suspension hyaluronic acid was added. Three weeks after grafting, psoralen plus ultraviolet A (PUVA) or ultraviolet B (UVB) therapy was started. Residual leukodermic areas were subsequently retreated. RESULTS: Repigmentation was observed within 2-4 weeks and continued to increase for 3 months after treatment. In all patients, 85-100% repigmentation was achieved. A temporary slight color mismatch was visible in all patients. The most homogeneous repigmentation was obtained 5 months after treatment.

CONCLUSION: This modified procedure seems to be a simple and promising treatment for larger vitiliginous areas.

LASER

Treatment of vitiligo with the 308-nm excimer laser: A pilot study.

Spencer JM, Nossa R, Ajmeri J.

Division of Dermatologic Surgery and the Department of Dermatology, Mount Sinai School of Medicine.

J Am Acad Dermatol 2002 May;46(5 Pt 1):727-31 Abstract quote
BACKGROUND: Present vitiligo therapies require many months of treatment and often result in disappointing outcomes. Common therapeutic options include phototherapy with psoralens plus ultraviolet A (UVA) radiation and broadband or narrowband UVB radiation phototherapy. Some of these modalities require regular phototherapy sessions several times a week for up to a year to achieve a therapeutic response. Targeted phototherapy with single-wavelength laser light is a treatment alternative that may prove to be a time-efficient and effective therapeutic option for the management of vitiligo.

METHODS: This intervention study was designed as a before and after trial with a single arm. Twenty-nine patches of vitiligo from 18 patients (6 males and 12 females) were treated at the start of the study. Vitiligo patches were treated by using a 308-nm xenon-chloride excimer laser. Lesions were treated 3 times a week for a maximum of 12 treatments. Treatment was withheld if sunburn was observed and held until resolution. All patients had untreated vitiligo patches that served as control sites.

RESULTS: Twenty-three vitiligo patches from 12 patients received at least 6 treatments and resulted in some repigmentation in 57% of the treated patches. Eleven vitiligo patches from 6 patients received all 12 treatments and resulted in some repigmentation in 82% of the treated patches. Untreated control patches remained unchanged.

CONCLUSION: This degree of repigmentation in a period of 2 to 4 weeks is much higher than that achieved with any other present vitiligo therapy. The xenon-chloride excimer laser may represent a new treatment modality for the management of stable vitiligo.

MELANOCYTE TRANSPLANTATION

Treatment of vitiligo by transplantation of cultured pure melanocyte suspension: Analysis of 120 cases.

Chen YF, Yang PY, Hu DN, Kuo FS, Hung CS, Hung CM.

Department of Dermatology and Cell Culture Laboratory of the Department of Medical Research and Pigment Cell Research Center, Show Chwan Memorial Hospital, Changhua City, Taiwan; Graduate Institute of Natural Products, Kaohsiung Medical University; and Tissue Culture Center, The New York Eye and Ear Infirmary, New York Medical College. USA.

J Am Acad Dermatol. 2004 Jul;51(1 Pt 1):68-74. Abstract quote

BACKGROUND: Despite the availability of various medical treatments for vitiligo, a large percentage of patients fail to achieve satisfactory results. Surgical techniques offer a potential solution for patients with vitiligo who fail to respond to medical treatments.

OBJECTIVE: We evaluated the practicality in treating vitiligo by using cultured autologous pure melanocytes and investigated the different results among stable localized vitiligo, stable generalized vitiligo, and active generalized vitiligo.

METHODS: In all, 120 patients with vitiligo were treated with transplantation of autologous cultured pure melanocyte suspension after carbon-dioxide laser abrasion.

RESULTS: Patients with stable localized vitiligo experienced the highest percentage of excellent repigmentation with 84% achieving 90% to 100% coverage, followed by 54% of patients with stable generalized vitiligo, whereas only 14% of patients with active generalized vitiligo experienced good repigmentation. Age and sex of the patients, and size and location of the lesions, did not show significant influence on the results of transplantation.

CONCLUSION: Autologous cultured pure melanocyte suspension combined with carbon-dioxide laser abrasion is an effective treatment for patients with stable vitiligo who fail to respond to medical treatments, especially for those with stable localized vitiligo.

PHOTOTHERAPY

Narrow-band ultraviolet B is a useful and well-tolerated treatment for vitiligo

Lubomira Scherschun, etal.

J Am Acad Dermatol 2001;44:999-1003 Abstract quote

Background: The treatment of vitiligo remains a challenge.

Objective: The purpose of this article is to review our results and experience with narrow-band ultraviolet (UV) B phototherapy for vitiligo.

Methods: This is a retrospective analysis of our experience and results with patients with vitiligo who were treated with narrow-band UVB between November 1998 and November 1999. Narrow-band UVB phototherapy was given as monotherapy 3 times a week. The starting dose was 280 mJ/cm2, with 15% dose increments at each subsequent treatment.

Results: Seven patients were able to be evaluated for the purposes of this analysis. Their ages ranged from 19 to 59 years (mean, 37.6 years). Three patients had Fitzpatrick skin phototype IV and V, and 4 had phototypes II and III. Five of the 7 patients achieved more than 75% repigmentation with a mean of 19 treatments; the mean duration of disease was 13 months. The remaining two patients had 50% and 40% repigmentation after 46 and 48 treatments, respectively. Their mean duration of disease was 132 months. Adverse effects were mild erythema and pruritus.

Conclusion: This treatment protocol resulted in rapid repigmentation in many patients, including those with skin phototypes IV and V. In accordance with previous studies, this report indicates that narrow-band UVB is a useful and well-tolerated therapy for vitiligo.

TACROLIMUS

Topical tacrolimus therapy for vitiligo: Therapeutic responses and skin messenger RNA expression of proinflammatory cytokines.

Grimes PE, Morris R, Avaniss-Aghajani E, Soriano T, Meraz M, Metzger A.

Vitiligo and Pigmentation Institute of Southern California, and the Division of Dermatology, and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles USA.

J Am Acad Dermatol. 2004 Jul;51(1 Pt 1):52-61. Abstract quote

BACKGROUND: Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo.

OBJECTIVE: This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls.

METHODS: Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were determined by real-time quantitative polymerase chain reaction.

RESULTS: At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-gamma in involved and adjacent uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF-alpha expression in involved and uninvolved skin (P=.01 and P=0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha expression decreased in the depigmented and adjacent uninvolved skin (P <.001). There was no statistically significant change in IL-10 or IFN-gamma posttreatment.

These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be associated with repigmentation of vitiligo.

A Double-blind Randomized Trial of 0.1% Tacrolimus vs 0.05% Clobetasol for the Treatment of Childhood Vitiligo.

Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB, Ortiz CA, Torres-Rubalcava AB.

Dermatology Department, Hospital Central "Dr Ignacio Morones Prieto", Public Health Department, School of Medicine, and the Graphic Design School, Universidad Autonoma de San Luis Potosi, San Luis Potosi, Mexico.

Arch Dermatol 2003 May;139(5):581-5 Abstract quote
OBJECTIVE: To assess the safety and efficacy of topical 0.1% tacrolimus vs 0.05% clobetasol propionate.

DESIGN: Randomized double-blind trial.

SETTING: Department of Dermatology, Hospital Central "Dr Ignacio Morones Prieto," San Luis Potosi, Mexico.

PARTICIPANTS: From 20 children with vitiligo, 2 symmetrical lesions of about the same size and evolution time were selected. They were devoid of any topical or systemic therapy for 2 months prior to inclusion.Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period.Main Outcomes Measures The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit. The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program. Characteristics of pigment, time of response, symptoms, telangiectasias, and atrophy were evaluated every 2 weeks.

RESULTS: Eighteen (90%) of the 20 patients experienced some repigmentation. The mean percentage of repigmentation was 49.3% for clobetasol and 41.3% for tacrolimus. Lesions in 3 patients using clobetasol presented atrophy, and 2 lesions incurred telangiectasias; tacrolimus caused a burning sensation in 2 lesions.

CONCLUSIONS: Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids, and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods.

Topical tacrolimus for repigmentation of vitiligo.

Grimes PE, Soriano T, Dytoc MT.

Vitiligo and Pigmentation Institute of Southern California, and the Division of Dermatology, University of California, Los Angeles; and the Division of Dermatology and Cutaneous Sciences, University of Alberta.
J Am Acad Dermatol 2002 Nov;47(5):789-91 Abstract quote
We describe 6 patients with generalized vitiligo who responded to treatment with tacrolimus ointment. Moderate to excellent repigmentation was achieved in 5 patients.

Although the number of cases in this noncontrolled, nonblinded series is small, tacrolimus ointment may be an efficacious and safe treatment option for vitiligo.

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Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008

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DISEASE ASSOCIATIONS	CHARACTERIZATION
BONE MARROW TRANSPLANTATION
Transfer of vitiligo after allogeneic bone marrow transplantation. Alajlan A, Alfadley A, Pedersen KT. Department of Medicine, King Faisal Specialist Hospital and Research Centre.	J Am Acad Dermatol 2002 Apr;46(4):606-10 Abstract quote Adoptive transfer of donor immunity has been demonstrated in animals after bone marrow transplantation (BMT). In humans, several autoimmune diseases have been similarly transferred. Although BMT may, per se, be associated with a modulation of the recipient's immune system, which could trigger or even cause autoimmune diseases, both animal experiments and experience with humans show the likeliness of adoptive transfer of donor immunity to the recipient. We describe a patient with multiple myeloma in whom generalized vitiligo developed within 3 months after allogeneic BMT from his HLA-matched sister with vitiligo. We believe that a form of adoptive transfer of donor immunity to the recipient might play a role in the development of vitiligo. In spite of this, neither de novo development of vitiligo in a genetically predisposed patient nor autoimmune phenomena associated with graft-versus-host disease can be completely excluded as a contributing factor for development of vitiligo in our patient. To our knowledge, this is the first case report of transfer of vitiligo after BMT from a donor with vitiligo.
IDIOPATHIC CD4+ T-CELL LYMPHOCYTOPENIA
Idiopathic CD4+T-cell lymphocytopenia associated with vitiligo. Yamauchi PS, Nguyen NQ, Grimes PE. Division of Dermatology, University of California Los Angeles School of Medicine, and the Vitiligo and Pigmentation Institute of Southern California.	J Am Acad Dermatol 2002 May;46(5 Pt 1):779-82 Abstract quote The syndrome of idiopathic CD4(+) T lymphocytopenia (ICTL) is defined as the persistent depletion of peripheral blood CD4(+) T lymphocytes below 300 cells/mm(3) or less than 20% of the total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. To date no known viral origin has been identified. ICTL has a variable clinical course ranging from patients with minimal symptoms to those who have died from opportunistic infections. We report a case of a 32-year-old white man with a long history of vitiligo that is associated with ICTL. He also had incidental psoriasis. The correlation between ICTL and autoimmune vitiligo suggests an aberration in the immune surveillance that leads to an abnormal response of CD4(+) T lymphocytes in the host.
VOGT-KOYANAGI-HARADA DISEASE
	J Am Acad Dermatol 2001;44:129-131 Inflammatory vitiligo with thin raised erythema around depigmented areas
SQUAMOUS CELL CARCINOMA
Squamous cell carcinoma in a patient with generalized vitiligo Seung-Lee Seo, MD Il-Hwan Kim, MD,PhD Seoul, Korea	J Am Acad Dermatol 2001;45:S227-9 Abstract quote Association of vitiligo and skin cancer has been a subject of controversy. Occurrence of skin cancer in long-lasting vitiligo is rare, and PUVA therapy-associated squamous cell carcinomas are not reported until recent years. We report a case of squamous cell carcinoma and actinic keratosis in long-lasting vitiliginous patches in a patient with generalized vitiligo who did not receive PUVA therapy.
Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo. Schallreuter KU, Tobin DJ, Panske A. Institute for Pigmentary Disorders, Greifswald, Germany.	Dermatology 2002;204(3):194-201 Abstract quote Background: It is well established that ultraviolet radiation is related to non-melanoma skin cancer (NMSC) in Caucasians. Considering that patients with vitiligo have often no protective pigment in sun-exposed depigmented/white skin together with severe oxidative stress due to accumulation of millimolar epidermal hydrogen peroxide (H(2)O(2)), it would be expected that these patients develop a higher risk for early photodamage and NMSC. However, scattered reports on low patient numbers documented no increased risk for sun-induced skin cancers in this disease. Objective: The aim of this study was to validate the possible photodamage and the development of epidermal neoplasia in a randomly selected larger patient group with emphasis on each patient's sun sensitivity and the history of solar habits. Furthermore we wished to compare histological signs for epidermal photodamage in a random representative patient group (mean age >30 years) and age-matched healthy controls. Methods: One hundred and thirty-six randomly selected patients (females n = 93; males n = 43; mean age 42.4 years, range 14-70 years) were included in this study. To assess signs of photodamage and skin cancer, all patients underwent a thorough full-body examination by Wood's light and dermatoscopy. In order to learn about each patient's individual sun sensitivity and solar habits, a direct questionnaire was used. In addition full skin punch biopsies of sun-exposed depigmented/pigmented skin were taken under local anaesthesia and evaluated by light microscopy. Results: There was no evidence for sun-related damage in the entire patient group, despite a significant number of positive cases with a history of sunburns in early childhood and continuous accumulation of epidermal H(2)O(2). Histological examination of the epidermis showed no signs of increased photo-ageing and confirmed the absence of apoptosis in these patients. Furthermore surprisingly there was no increased risk for photosensitivity disorders, i.e. polymorphous light reaction, solar urticaria and acute actinic dermatitis. Conclusion: The results of this study confirm in a large group of patients with vitiligo the absence of an expected high risk for sun-induced damage and skin cancer. Based on these results together with a recent report on increased functional wild-type p53 expression in these patients we would like to propose that in vitiligo there may be a direct association between this important tumour suppressor and the absence of photodamage and NMSC.

HISTO-PATHOLOGICAL VARIANTS	CHARACTERIZATION
GENERAL
Histopathologic features in vitiligo. Kim YC, Kim YJ, Kang HY, Sohn S, Lee ES. Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.	Am J Dermatopathol. 2008 Apr;30(2):112-6. Abstract quote Nevus depigmentosus is a congenital disorder characterized by a nonprogressive hypopigmented lesion, which may not be apparent at birth. Thus, it is sometimes difficult to differentiate vitiligo from nevus depigmentosus only by clinical features. We postulated that the histologic changes in lesional and perilesional skin might be different in the 2 conditions. We took biopsies from both lesional and perilesional skin of 100 cases of vitiligo to assess the number of melanocytes, the amount of melanin, dermal inflammatory infiltrate, and other changes. We compared them with 30 cases of nevus depigmentosus. Histologically, lesions of vitiligo showed more basal hypopigmentation and dermal inflammation than perilesional normal skin. With Fontana-Masson staining, 16% of cases of vitiligo showed the presence of melanin. The ratio of pigmented area to epidermal area was 0.06% in vitiligo, whereas 17% in perilesional normal skin and 8.9% in nevus depigmentosus. In NKI/beteb staining, 12% of vitiligo showed the presence of melanocytes, and their average number was 7.68 per square millimeter. The number of melanocytes was also decreased in nevus depigmentosus but not as much as in vitiligo. We also confirmed the presence of melanocytes in 1 of 3 cases of vitiligo by electron microscopy. In conclusion, there are a few melanocytes and melanin in some cases of vitiligo. Therefore, the diagnosis of vitiligo should be made considering these points.
Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation. Le Poole IC, van den Wijngaard RM, Westerhof W, Dutrieux RP, Das PK. Department of Dermatology, Amsterdam University, The Netherlands.	J Invest Dermatol 1993 Jun;100(6):816-22 Abstract quote There is a long-standing controversy over whether melanocytes in vitiligo lesions are actually lost or are still present but inactivated. Resolving this matter is essential for understanding the underlying pathology and for the development of treatment. Standard methods of detecting melanocytes are based on active melanin synthesis. However, it is possible that inactive melanocytes remain in the lesions. There are no methods presently available to detect such dormant melanocytes. Using a panel of one polyclonal and 17 monoclonal antibodies directed against melanocytic cells (largely selected by the European Organisation for Research and Treatment of Cancer Melanoma Group for diagnostic and therapeutic purposes), we investigated the absence or inactivation of melanocytes in vitiligo by immunohistochemistry. Results using this panel of antibodies on frozen skin sections suggest that melanocytes are indeed absent in the lesions. However, in epidermal split-skin preparations, residual staining was occasionally observed. To determine whether the staining obtained was due to degenerated melanocytes, confocal laser scanning microscopy was used. Immunofluorescent staining using the antibody NKI-beteb confirmed this to be the case. The results presented here strongly suggest that melanocytes are indeed lost in vitiligo lesions.
Melanocytes are not absent in lesional skin of long duration vitiligo. Tobin DJ, Swanson NN, Pittelkow MR, Peters EM, Schallreuter KU. Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, UK.	J Pathol 2000 Aug;191(4):407-16 Abstract quote This paper provides evidence that melanocytes are still present in the depigmented epidermis of patients with vitiligo even after stable disease of 25 years' duration. Melanocyte cultures were successfully established from depigmented epidermal suction blister tissue of all 12 randomly selected patients and these cells produced melanin. Even under in vitro conditions, vacuolation of melanocytes was demonstrated in five patients with active disease, which was reversible upon exogenous addition of bovine catalase to the culture medium. Full skin biopsies from 17 patients with vitiligo, obtained from depigmented and normally pigmented areas, confirmed the involvement of melanocytes, keratinocytes, and Langerhans cells in this disorder. In addition, the presence of clustered and single pre-melanosomes in basal and supra-basal keratinocytes of lesional and normal epidermis, as well as the retention of single melanocytes in lesional epidermis, was demonstrated by light and electron microscopy. Upon topical application of a narrow band UVB-activated pseudocatalase, vacuolation, granulation, and dilatation of the endoplasmic reticulum completely recovered, but the ectopic pre-melanosome shedding remained. Taken together, these observations indicate that melanocytes are never completely absent in the depigmented epidermis and that these melanocytes can recover their functionality in vivo and in vitro upon the removal of hydrogen peroxide. Furthermore, this study supports the concept that vitiligo involves the entire epidermal unit in both depigmented and 'normal' pigmented skin.
VARIANTS
TRICHOME VITILIGO
Clinical and histopathologic characteristics of trichrome vitiligo. Hann SK, Kim YS, Yoo JH, Chun YS. Department of Dermatology, Yonsei University College of Medicine, and the Pochon CHA Medical College, Pundang CHA Hospital.	J Am Acad Dermatol 2000 Apr;42(4):589-96 Abstract quote BACKGROUND: The term trichrome vitiligo describes lesions that have a tan zone of varying width between normal and totally depigmented skin, which exhibits an intermediate hue. However, the pathogenesis and the histopathologic characteristics of trichrome vitiligo are unknown. OBJECTIVE: Our purpose was to investigate the clinical and histopathologic characteristics and the pathogenesis of trichrome vitiligo. METHODS: Four punch biopsy specimens were taken from 21 patients with trichrome vitiligo; they were from vitiliginous skin, light brown skin, perilesional normal skin, and normal skin as far as 5 cm from the nearest vitiligo spot. The sections were stained with hematoxylin-eosin; in selected cases, we performed immunohistochemical staining with S-100 protein and CD1a. RESULTS: Trichrome vitiligo occurred most frequently on the trunk in active vitiligo vulgaris. Focal vacuolar degeneration of the basal cell layer and mild inflammatory cell infiltration of the epidermis and dermis were more prominent in light brown skin and perilesional normal skin than in vitiliginous skin and normal skin. The number of melanocytes was decreased in light brown skin compared with perilesional normal skin (P <.05) and in vitiliginous skin compared with light brown skin (P <.05); a few melanocytes were observed even in skin affected by trichrome vitiligo. The number of Langerhans cells was increased in the epidermis of light brown skin and perilesional normal skin compared with vitiliginous and normal skin (P <.05). PUVA therapy yielded excellent repigmentation. CONCLUSION: Trichrome vitiligo is a variant of active vitiligo. The changes of melanocytes, keratinocytes, and Langerhans cells may be involved in the pathogenesis of depigmentation in trichrome vitiligo.

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Gross Appearance and Clinical Variants
Histopathological Features and Variants
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DIFFERENTIAL DIAGNOSIS	CHARACTERIZATION
NEVUS DEPIGMENTOSUS
Clinical and histopathologic characteristics of nevus depigmentosus. Kim SK, Kang HY, Lee ES, Kim YC. Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.	J Am Acad Dermatol. 2006 Sep;55(3):423-8. Abstract quote BACKGROUND: Nevus depigmentosus (ND) is known to be a rare congenital, nonprogressive disorder characterized by a hypopigmented lesion that remains stable over time. There have been only few studies of clinical and histopathologic characteristics of ND, and the etiopathogenesis is not fully established. OBJECTIVE: The purpose of this study was to investigate the clinical and histopathologic characteristics of ND. METHODS: A clinical survey was carried out with 60 patients given the diagnosis of ND. Punch biopsies (2 mm) from lesional and perilesional normal skin were performed. The sections were stained with hematoxylin-eosin, Fontana-Masson, antibodies to S-100 protein, MART-1, NKI/beteb, CD1a, CD3, CD20, and CD68. RESULTS: The lesions were usually present before the age of 3 years (68.3%), but some lesions appeared later in childhood (31.7%). In all, 27 patients (45%) had one lesion, but there were 14 patients (23.3%) who had more than 10 lesions. Fontana-Masson stain showed that the amount of melanin was significantly decreased in ND skin compared with perilesional normal skin. Melanocyte counts were significantly decreased in ND skin when stained with antibodies to GP-100 and MART-1. However, there were no significant differences in the number of melanocytes identified as S-100 protein-positive cells. There were no significant differences in histologic findings or dermal inflammatory infiltrates between ND skin and perilesional normal skin. LIMITATIONS: Only 29 patients (48.3%) were followed up, and the average follow-up period after initial diagnosis was relatively short (68 months); therefore, these overall results may not be representative of the clinical course of the patients. CONCLUSION: Only 18 patients (30.0%) presented with ND since birth and only 27 patients (45.0%) had one lesion. Both the amount of melanin and the number of melanocytes in ND skin were decreased in patients with ND. Therefore, both clinical and histologic findings should be considered together to make a diagnosis of ND.