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itiligo Updateebat M. Halder, MD, and Johnathan L. Chappell, MD

Vitiligo is an acquired dyschromia of the skin in which there is a loss of epidermalmelanocytes. The prevalence of vitiligo is approximately 1% in the United States and0.1-2% worldwide. The exact pathogenesis of vitiligo remains elusive and is likely multi-factorial. After completing this update, participants should be able to discuss the epide-miology of vitiligo and summarize the proposed mechanisms for development of thisdisease. In addition, they should be able to discuss physical findings, approach to thepatient, and some of the therapeutic modalities for this disorder.Semin Cutan Med Surg 28:86-92 © 2009 Elsevier Inc. All rights reserved.

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itiligo occurs worldwide, with a prevalence of �2%. Inthe United States, its estimated incidence is 1%. The

isease usually begins in childhood or young adulthood withpeak onset at 10-30 years. All races are affected, and both

exes are equally affected; however, a female preponderanceas been reported. This discrepancy may potentially bekewed by increased reporting of cosmetic concerns by fe-ale patients. Vitiligo can be psychologically devastating for

he affected patient. This is especially true in patients witharker skin because of the great contrast between the color ofitiliginous skin and surrounding normal skin. Vitiligo canffect quality of life, self-esteem, marriage, and employment,specially in darker-skinned individuals and in certain cul-ures because of confusion with leprosy and other contagiouskin diseases. Loss of pigment may be viewed by patients as ahreat to racial identity.

tiopathogenesisitiligo is multifactorial and polygenic. The precise patho-enesis remains elusive; however, several theories have beenroposed to explain the loss of epidermal melanocytes in thisisorder. Proposed mechanisms fall under the rubrics of au-oimmune, biochemical, oxidant-antioxidant, neural, and vi-al. Studies have also pointed to a significant role of geneticusceptibility to vitiligo.

enetics of Vitiligoitiligo is inherited in a non-Mendelian pattern and is char-cterized by incomplete penetrance, multiple susceptibility

epartment of Dermatology, Howard University College of Medicine,Washington, DC.

ddress reprint requests to Rebat M. Halder, Department of Dermatology,Howard University College of Medicine, 2041 Georgia Avenue, N.W,

VWashington, DC 20060. E-mail: rhalder@howard.edu.

6 1085-5629/09/$-see front matter © 2009 Elsevier Inc. All rights reserved.doi:10.1016/j.sder.2009.04.008

oci, and genetic heterogeneity. Inheritance may involveenes associated with melanin biosynthesis, response to ox-dative stress, and regulation of autoimmunity. Because of therequent association of vitiligo with autoimmune diseases,here have been investigations of possible HLA associationsn vitiligo. Several haplotypes have been associated with viti-igo in more than one study.1,2

The catalase gene has been implicated in the pathogenesisf vitiligo. Most likely a C/T single nucleotide polymorphismn exon 9 of the catalase gene is responsible.3 Reduced cata-ase enzyme activity has been demonstrated in the epidermisf lesional and nonlesional skin in patients with vitiligo.4

atalase is a peroxisomal enzyme found in nearly all organ-sms exposed to oxygen that catalyzes the decomposition ofydrogen peroxide to water and oxygen. Therein, it serves torevent cell damage by highly reactive oxygen radicals.

ole of the Immune Systemhe association of vitiligo with autoimmune conditions isell established. Thyroid disorders, particularly Hashimoto’s

hyroiditis and Graves’ disease, are commonly associatedith vitiligo, as are other endocrinopathies, such as Addi-

on’s disease and diabetes mellitus. Alopecia areata, perni-ious anemia, systemic lupus erythematosus, inflammatoryowel disease, rheumatoid arthritis, psoriasis, and autoim-une polyglandular syndrome also are associated, though

he significance of some of these associations is debated. Theost compelling argument for an autoimmune pathogenesis

s the demonstration of circulating autoantibodies to melano-ytes in the serum of patients with vitiligo. Autoantibodiesirected specifically against melanocyte cell surface antigensave the ability to kill melanocytes in vivo and in vitro. The

evels of these autoantibodies seem to correlate with diseasextent and activity. One of the autoantigens identified is

IT 40.1 Tyrosinase and TRP-1 and �2 have been identi-

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Vitiligo update 87

ed as autoantigens as well, but data supporting this claimave been conflicting.5 Some patients with vitiligo haventibodies to melan A/MART-1, a melanocyte differentia-ion antigen.6 SOX transcription factors, which are involvedn the differentiation of tissue derived from the neural crest,ave been identified as melanocytic antigens in vitiligo asso-iated with the polyendocrine syndrome.7 Antiorgan anti-odies, such as antibodies to thyroglobulin, thyroid micro-omes, and gastric parietal cells, also are frequently elevatedn patients with vitiligo as compared with healthy controlatients.1 Speculation abounds that codon-54 polymor-hism in the mannose-binding lectin 2 gene may play a role

n susceptibility to vitiligo. Mannose-binding lectin is a cal-ium-dependent lectin that causes predisposition to infec-ions and autoimmune diseases.8

xidant-Antioxidant Role in Vitiligoxidative stress may also play an important pathogenic role

n vitiligo. Several studies suggest that accumulation of freeadicals toxic to melanocytes leads to their destruction. Cul-ured melanocytes and the serum of patients with vitiligoften have increased nitric oxide levels, suggesting that nitricxide could lead to autodestruction of melanocytes. Com-ared with control patients, the red cells of vitiligo patientsave lower levels of glutathione, which helps prevent freeadical mediated injury.9 Thus, vitiligo patients may be sub-ect to a greater level of oxidative stress.

eural Theoryegmental vitiligo often occurs in a dermatomal pattern. Thisbservation led to a neural hypothesis that proposes certainhemical mediators released from nerve endings may causeecreased melanin production. Elevated neuropeptide Y lev-ls have been demonstrated in skin affected by vitiligo.10

ecreased sweating occurs in some patches of segmental viti-igo, and some patients have been shown to have mild degen-rative or regenerative changes in axons and Schwann cells inhe depigmented areas.

iralytomegalovirus (CMV) DNA has been identified in skiniopsy specimens of some patients with vitiligo, which raiseshe question of whether there is viral-induced damage toelanocytes in subsets of patients with vitiligo.11 The possi-

le involvement of other viruses, such as hepatitis C, HIV,nd Epstein-Barr virus has been suggested by some au-hors.12,13

onvergence Theorylthough all the aforementioned hypotheses are attractive, it

s likely that vitiligo is a result of the convergence of several ofhese pathologic pathways. Most experts agree that vitiligoay indeed be a syndrome rather than a single entity.

linical Findingsatients present with 1 to several amelanotic macules that

ppear chalk- or milk-white in color. There is no epidermal v

hange and usually no erythema; however, very occasionally,nflammation can be seen at the advancing edge of lesions.esions are often symmetric and usually enlarge centrifugally

n size with time. The increase in size corresponds with aubstantial loss of functioning epidermal and, sometimes,air follicle melanocytes. Lesions are typically well demar-ated, but the borders may be scalloped. Lesions are accen-uated with Wood’s lamp examination. Initial lesions occurost frequently on the hands, forearms, feet, and face, al-

hough they may appear anywhere, including the mucousembranes. Facial vitiligo often favors a periorificial distri-

ution.14

lassification of Vitiligoitiligo is classified as segmental, acrofacial, generalized, andniversal or by pattern of involvement as focal, mixed, anducosal types.

● Focal vitiligo is usually a solitary macule or a few scat-tered macules in 1 area, most commonly in the distribu-tion of the trigeminal nerve, although the neck andtrunk are also commonly involved. This form occursmore commonly in children.

● Segmental vitiligo presents as unilateral macules in adermatomal or quasi-dermatomal distribution. Thistype tends to have an early age of onset and, unlike theother types, is not associated with thyroid disease orother autoimmune diseases. Alteration of neural pep-tides has been implicated in the pathogenesis. Morethan one half of patients with segmental vitiligo havepoliosis.

● Acrofacial vitiligo presents as depigmentation of the dis-tal fingers and periorificial areas.

● Generalized vitiligo is also termed vitiligo vulgaris. Thisis the most common pattern. Depigmented patches arewidely and usually symmetrically distributed.

● Universal vitiligo presents as depigmented macules andpatches over most of the body and can be associatedwith multiple endocrinopathy syndrome (Fig. 1).

● Mucosal vitiligo involves only the mucous membranes(Fig. 2).

n patients of darker skin type, there is great contrast betweenepigmented and normal skin as shown in Figs. 3 and 4. This isften psychologically devastating.

linical Variantsrichrome vitiligo is characterized by both depigmented andypopigmented macules in addition to normally pigmentedkin. The natural evolution of the hypopigmented areas isrogression to full depigmentation. Quadrichrome vitiligoefers to the additional presence of marginal or perifollicularyperpigmentation. This variant is recognized more fre-uently in darker skin types, particularly in areas of repig-entation. Pentachrome vitiligo has also been reported with

dditional blue–gray hyperpigmented macules, representingreas of melanin incontinence. Occasionally, patients with

itiligo may present with an unusual variant called the con-

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etti type. These patients have several tiny, discrete, hy-omelanotic macules. Inflammatory vitiligo is characterizedlinically by erythema at the margins of vitiligo macules.

ifferential Diagnosiseveral diseases can be mistaken for vitiligo, including butot limited to Tinea versicolor, piebaldism, idiopathic guttateypomelanosis, and progressive macular hypomelanosis.inea versicolor is a superficial yeast infection that can lead to

oss of pigment in darker-skinned individuals. It presents asight-colored macules typically on the upper trunk and chest,ith a fine dry surface scale. Piebaldism is an autosomal-ominant disorder in which there is an absence of melano-ytes from the affected areas of the skin. It usually presents at

igure 1 Universal vitiligo in an Asian woman.

igure 2 Mucosal involvement of the lip with vitiligo in an African-

mmerican man.

irth with depigmented areas that are usually near the mid-ine on the front, including a white forelock. Idiopathic gut-ate hypomelanosis presents with multiple small discretehite macules on the trunk or on sun-exposed areas of the

imbs. Progressive macular hypomelanosis is a common dis-rder that is often misdiagnosed. It is most common in Afri-an-American patients originating from tropical countries. Its characterized by ill-defined, nummular, nonscaly hypop-gmented macules on the trunk, often confluent in andround the midline and rarely extending to the proximalxtremities and head and neck.14

aboratory Testshe diagnosis of vitiligo is based primarily on clinical find-

ngs. However, given the association between vitiligo andther autoimmune diseases (a history of autoimmune diseasen a family member is obtained in 32% of patients), severalcreening laboratory tests are helpful, including thyroid-timulating hormone, antinuclear antibody, and completelood count. Clinicians should also consider testing for se-um antithyroglobulin and antithyroid peroxidase antibod-es, especially if patient and family history indicates so. Anti-hyroid peroxidase antibodies, in particular, are regarded as aensitive and specific marker of autoimmune thyroid disor-ers (Table 1).

istologyesional skin of vitiligo patients lacks melanocytes. A super-cial dermal lymphocytic infiltrate may be observed at the

igure 3 Disfiguring facial involvement with vitiligo in an African-merican man.

argin of vitiliginous skin, particularly in early lesions. This

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Vitiligo update 89

nding is consistent with cell-mediated immune processesestroying melanocytes.15

pproach to theatient with Vitiligo

n the guidelines for diagnosis and management of vitiligo byawkrodger et al,14 the algorithm was based on studies ofarious levels of evidence. Levels of evidence were defined asollows:

1�� High-quality meta-analyses, systematic reviews ofrandomized controlled trials (RCTs), or RCTs with avery low risk of bias

1� Well-conducted meta-analyses, systematic reviews ofRCTs, or RCTs with a low risk of bias

1-Meta-analyses, systematic reviews of RCTs, or RCTswith a high risk of bias

2�� High-quality systematic reviews of case-control orcohort studies; and

High quality case-control or cohort studies with a very lowrisk of confounding, bias, or chance and a high proba-bility that the relationship is causal

2� Well-conducted case-control or cohort studies with alow risk of confounding, bias, or chance and a moderateprobability that the relationship is causal

2-Case-control or cohort studies with a low risk of con-founding, bias, or chance and a significant risk that the

igure 4 Disfiguring facial involvement with vitiligo in a Hispanic man.

relationship is not causal *

3. Nonanalytical studies, for example, case reports, caseseries

4. Expert opinion.14

itiligo can be a psychologically devastating disease that hassignificant impact on quality of life and self-esteem. Vitiligoay cause social isolation and significant depression. Some

ssessment of the impact of vitiligo on the patient’s quality ofife should be made at the initial consultation (level of evi-ence 2�A).Women are more severely affected with respect to quality

f life, being more likely to be depressed about their appear-nce and more likely to internalize stigmatization and at-ribute an internal cause (level of evidence 3). Psychologicalffects appear to be more prominent when visible body areasre affected (level of evidence 3). Vitiligo has an impact sim-lar to that of psoriasis on a patient’s quality of life. Psycho-ogical interventions should be offered as a way of improvingoping mechanisms in patients with vitiligo. Group therapynd individual therapy were both shown to be of benefit inhe works of Papadopolous et al.16 Also, parents of affectedhildren should be offered psychological counseling (level ofvidence 4).14

There are several treatment options available to vitiligoatients. Most treatments are intended to restore pigment tohe skin. Each treatment has advantages and disadvantages.o treatment is appropriate for every patient with vitiligo.

unscreensunscreens help prevent sunburn and in effect lessen photo-amage, which decreases the chance that an isomorphic re-ponse of Koebner will occur. In addition, sunscreens de-rease tanning of the uninvolved skin and therefore lessen theontrast with vitiliginous lesions.

osmeticsany patients find cosmetic cover-ups to be a valuable treat-ent option. Areas of depigmentation, especially on the face,eck, or hands can be covered with conventional make-up,elf-tanning products, or other topical dyes. Advantages ofosmetics are that they offer limited cost, minimal side ef-ects, and ease of application. In children and adults of skinypes I and II, it is appropriate to consider whether the initialpproach may be to use no active treatment other than cos-etics and sunscreen (level of evidence 4).14

opical Corticosteroidsopical steroids are indicated for the treatment of limitedreas of vitiligo and are often the first line of therapy in

able 1 Screening Laboratory Tests in Patients With Vitiligo

Thyroid-stimulating hormoneComplete blood countAntinuclear antibodyAntithyroglobulin antibodies*Antithyroid peroxidase antibodies*

If patient and/or family history indicates.

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ediatric patients, although most experience is anecdotal.esions on the face seem to have the best response and lesionsn the neck and extremities with the exception of the fingersnd toes also have a favorable response.17 It is unclear whyesions on the face have a better response rate. Proposedheories are that the facial skin has greater permeability to theorticosteroids, a larger number of residual melanocytes inhe uninvolved skin, greater follicular reservoirs, or melano-yte damage that is more easily reversed. Lesions on the faceften repigment diffusely, whereas lesions elsewhere moreommonly repigment in a dot-like follicular pattern.

In children and adults with recent onset of vitiligo, treat-ent with a potent or very potent topical steroid should be

onsidered for a trial period of no more than 2 months (levelf evidence 1).14 Studies by both Kandil18 and Clayton19

how that the use of an ultrapotent or potent topical steroidan repigment vitiligo but only in a small proportion of pa-ients. Clayton found 15-25% repigmentation in 10 of 23atients and �75% repigmentation in 2 of 23 patients. Thether patients showed no repigmentation. Kandi18 found 90-00% repigmentation in 6 of 23 subjects and 25-90% in 3.ix patients showed “beginning pigmentation.” In childrennd adults with larger lesions, a medium-potency nonfluori-ated corticosteroid is often used, likely at the expense offficacy. Discretion must be exercised when using topicalteroids on and around the eyelids, as their use can increasentraocular pressure and exacerbate glaucoma.

Wood’s lamp examination can be used to monitor re-ponse to treatment. If no response is seen by 3 months,herapy should be discontinued. Maximum re-pigmentationay take 4 months or longer (there is a 30-40% response rateith 6 months of corticosteroid use). More darkly pigmentedatients may have a more favorable response to topical cor-icosteroids than those with lighter complexions. The ease ofpplication, compliance rate, and limited cost are the benefitsf using topical corticosteroids for treating limited vitiligo.ecurrence after treatment cessation and corticosteroid sideffects are the drawbacks. All patients, especially children,hould be monitored closely for side effects.

opical Immunomodulatorsopical tacrolimus ointment 0.03-0.1% is effective in repig-entation of vitiligo when applied twice daily in patientsith localized disease, particularly on the face and neck.opical tacrolimus is reported to be more effective whenombined with UVB or excimer laser therapy.20,21 In general,acrolimus ointment is considered safer for children thanopical steroids and should be considered as an alternative. Indults with symmetric types of vitiligo, topical pimecrolimushould be considered as an alternative to the use of a topicalteroid; in addition, its side effect profile is better than that ofhighly potent topical steroid. This conclusion is based on a

mall study conducted by Coskun and colleagues22 in whichhey compared topical pimecrolimus with topical clobetasol.imecrolimus resulted in 50-100% repigmentation in 8 of 10

atients. Similar results were seen in 7 of 10 patients treated i

ith clobetasol. No skin atrophy was seen in the pimecroli-us group, but burning was noted as a side effect.

opical Calcipotrioln a randomized, open, left vs right study by Chiaverini et al,23

he effect of calcipotriol, 0.005% was compared in symmetricarget lesions in 24 patients with localized and generalizeditiligo. After 3-6 months, no repigmentation was noted in 21f 23 patients. One had 5% repigmentation and 2 had repig-entation with and without calcipotriol. The use of topical

alcipotriol as a monotherapy is not recommended (level ofvidence 2��).14

seudocatalaseevels of catalase, an enzyme that is normally found in skinhat decreases damage from free radicals, have been reportedo be low in the skin of vitiligo patients. A replacement ther-py using an analog of normal human catalase, pseudocata-ase, in combination with narrow band UVB phototherapyas been reported to repigment some vitiligo patients andrevent disease progression.24-26

ystemic Therapiesystemic immunosuppressive drugs have many potentialide effects that are difficult to justify for a disease such asitiligo. However, systemic corticosteroids have been used asulse therapy with variable results and may prevent rapidepigmentation in active disease. In an open study con-ucted by Radakovic-Fijan et al,27 of 25 adults with activeeneralized types of vitiligo treated with oral dexamethasone0 mg twice weekly for 24 weeks, 22 of 25 had disease-rogression arrest. Side effects were common and includedeight gain, acne, menstrual irregularity, and hypertrichosis.ystemic immunosuppressive drugs to arrest progression ofitiligo cannot be recommended due to an unacceptable riskf side effects (level of evidence 2�A).14 There has been aase report of repigmentation in a patient with vitiligo beingreated for psoriasis with efalizumab.28 Biologics may be aotential therapeutic modality for vitiligo; however, theiride effect profile may preclude their use.

hototherapyopical or oral 8-methoxy psoralen combined with UVA ir-adiation (PUVA) is effective for treating vitiligo,29 althoughrequent treatments over several months are required. Afterxposure to UVA, psoralens covalently bind to DNA andnhibit cell replication. How this then leads to repigmenta-ion of vitiligo lesions is poorly understood. PUVA stimulatesyrosinase activity and melanogenesis in unaffected skin.UVA is also local immunosuppressive, and decreased ex-ression of vitiligo-associated melanocyte antigens has beeneported.

In vitiligo, melanocytes in the bulb and infundibulum ofhe hair follicle are often destroyed, but the lower and middleortion of the follicle as well as the outer root sheath arepared. PUVA stimulates follicular melanocytes to migrate

nto the epidermis and repopulate the surrounding vitiligi-

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Vitiligo update 91

ous skin, possibly because of the release of cytokines andhemoattractants from the epidermal keratinocytes.

If �20% of the body surface of a patient’s skin is involved,opical PUVA is sometimes used. However, unwanted sideffects are common and include cosmetically displeasing hy-erpigmentation of skin surrounding areas of vitiligo as theesult of inadvertent psoralen application, severe phototox-city, and severe pruritus. Oral psoralens are used for patientsith more extensive involvement or in patients who do not

espond to topical PUVA.Careful selection of patients with vitiligo for PUVA therapy

s very important. Although 70-80% of patients experienceome repigmentation with PUVA, �20% of patients achieveotal repigmentation. In general, vitiligo on the trunk, prox-mal extremities, and face responds well to PUVA, but lesionsn the distal extremities respond poorly. As with corticoste-oids, patients with a darker complexion tend to respondetter to PUVA, possibly because they tolerate greater PUVAxposures.30

Narrow-band UVB (NBUVB) irradiation is another optionor patients with vitiligo and is currently considered by manyo be the first choice for most patients.14 In patients withxtensive generalized vitiligo, NBUVB was more effectivehan topical PUVA (67% vs. 46% response rate, respec-ively).31 This comparison is not an appropriate one, how-ver, because topical PUVA is indicated for �20% skin sur-ace involvement with vitiligo and NBUVB is indicated for

20% skin surface involvement. A better comparison wouldave been between NBUVB and oral PUVA therapy which issed for �20% skin surface involvement with vitiligo.BUVB should be used in preference to oral PUVA in view of

vidence of greater efficacy and safety (level of evidence�).14 If no improvement is seen within 6 months, NBUVBherapy should be discontinued. In one study, 53% of chil-ren experienced more than 75% repigmentation afterBUVB therapy, and 6% showed complete repigmentation.gain, better pigmentation was achieved on the face, trunk,nd proximal extremities than on the distal extremities androin. Phototherapy should generally be reserved for patientsho can’t be adequately controlled by more conservative

reatments, who have widespread vitiligo, or who have local-zed vitiligo with a significant impact on quality of life.14

xcimer Laserxcimer (308 nm) laser has been studied in several trials for

ts efficacy in treating vitiligo. Therapy has been found to beost effective when used 3 times per week. Treatment peri-

ds of more than 12 weeks are necessary to obtain satisfac-ory repigmentation. The initial dose is 50-100 mJ per squarem. As with standard phototherapy, excimer laser producedhe best treatment results on the face. The least responsivereas were the hands and feet.32

epigmentationonobenzyl ether of hydroquinone (monobenzone) is the

nly agent available in the United States and Europe for de-

igmenting residual normal skin in patients with extensive

itiligo. Monobenzone is a phenolic toxin that destroys epi-ermal melanocytes after protracted use. Monobenzone canherefore produce a uniform depigmented state that is morecceptable for many patients than the contrast between nor-al and affected skin. Monobenzone is available as a 20%

ream and can be compounded to concentrations up to 40%.he individual using monobenzone should avoid direct con-

act with others for 1 hour after application, as contact mayause depigmentation of others’ skin.33 Monobenzone maylso be irritating and allergic sensitization may occur. Thisreatment should generally be reserved for adults who haveevere vitiligo with �50% depigmentation or extensive de-igmentation on the face or hands that cannot be repig-ented or for adults who choose not to seek repigmentation

nd can accept the permanence of never being able to tanlevel of evidence 4).14 The acceptance of appearance afterepigmentation by the patient is almost universal regardlessf the race or original skin color of the patient.

urgical Modalitiesurgical treatments should be reserved for cosmetically sen-itive sites in which there have been no new lesions, no Koeb-erization and no extension of the lesion in the previous 12onths (level of evidence 1��).14 In a study by Kim andang34 in which they performed suction blister transfer, re-

apse was seen in 40% of patients with progressive disease aspposed to 10% with stable disease. There are fortunatelyeveral very successful surgical treatments available, includ-ng split thickness grafts, suction blister grafts, mini punchrafts, and melanocyte transplant. A detailed discussion ofhese modalities is beyond the scope of this update but can beeviewed elsewhere.

onclusionsitiligo can be a very psychologically devastating disease.his is especially true in patients with skin of color. Vitiligoarries with it myriad psychosocial implications. In dealingith vitiligo patients, it may be of use to take a multidisci-linary approach and involve psychology or psychiatry con-ultation early in the treatment course. Treatments for vitiligoave various response rates and it may be necessary to useotational therapy to diminish side effects and to gain betterepigmentation response.

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2. Halder R, Nandedkar M, Neal K: Pigmentary disorders in pigmentedskins, In Halder R (ed): Dermatology and Dermatological Therapy ofPigmented Skin (ed 1), vol 5. New York, NY, Informa Healthcare, 2005

3. Gavalas NG, Akhtar S, Gawkrodger DJ, et al: Analysis of allelic variantsin the catalase gene in patients with the skin depigmenting disordervitiligo. Biochem Biophys Res Commun 345:1586-1591, 2006

4. Casp CB, She JX, McCormack WT: Genetic association of the catalasegene (CAT) with vitiligo susceptibility. Pigment Cell Res 15:62-66,2002

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0. Tu C, Zhao D, Lin X: Levels of neuropeptide Y in the plasma and skintissue fluids of patients with vitiligo. J Dermatol Sci 27:178-182, 2001

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6. Papadopoulos L, Bor R, Legg C: Coping with the disfiguring effects ofvitiligo: A preliminary investigation into the effects of cognitive-behav-ioural therapy. Br J Med Psychol 72:385-396, 1999

7. Cockayne S, Messenger AG, Gawkrodger D: Vitiligo treated with topi-cal corticosteroids: Children with head and neck involvement respondwell. J Am Acad Dermatol 46:964-965, 2002

8. Kandil E: Treatment of vitiligo with 0.1 percent betamethasone 17-valerate in isopropyl alcohol-a double-blind trial. Br J Dermatol 91:

457-460, 1974

9. Clayton R: A double-blind trial of 0.05% clobetasol propionate in thetreatment of vitiligo. Br J Dermatol 96:71-73, 1977

0. Passeron N, Ostovari T, Lacour JP, et al: Lack of efficacy of tacrolimusin the treatment of vitiligo in the absence of UV-B exposure. ArchDermatol 142:252, 2006

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