eMedicine Specialties > Dermatology > Diseases of Pigmentation

Vitiligo

Vlada Groysman, MD, Staff Physician, Department of Dermatology, University of Alabama School of Medicine
Naveed Sami, MD, FAAD, Assistant Professor Department of Dermatology, University of Alabama School of Medicine

Updated: Aug 8, 2008

Introduction

Background

Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes, and it is characterized by circumscribed depigmented macules and patches. It is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. Vitiligo affects 0.5-2% of the world population, and the average age of onset is 20 years.

Pathophysiology

Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and nongenetic factors. Although several theories have been proposed about the pathogenesis of vitiligo, the precise cause remains unknown. Generally agreed upon principles are an absence of functional melanocytes in vitiligo skin and a loss of histochemically recognized melanocytes, owing to their destruction. However, the destruction is most likely a slow process resulting in a progressive decrease of melanocytes. Theories regarding destruction of melanocytes include autoimmune mechanisms,¹ cytotoxic mechanisms, an intrinsic defect of melanocytes, oxidant-antioxidant mechanisms, and neural mechanisms.

Autoimmune destruction of melanocytes

The autoimmune theory proposes alteration in humoral and cellular immunity in the destruction of melanocytes of vitiligo. Thyroid disorders, particularly Hashimoto thyroiditis and Graves disease; other endocrinopathies, such as Addison disease and diabetes mellitus; and alopecia areata; pernicious anemia; inflammatory bowel disease; psoriasis; and autoimmune polyglandular syndrome are all associated with vitiligo. The most convincing evidence of an autoimmune pathogenesis is the presence of circulating antibodies in patients with vitiligo.² The role of humoral immunity is further supported by the observation that melanocytes are destroyed in healthy skin engrafted onto nude mice injected with vitiligo patient sera.³

In addition to the involvement of humoral immune mechanisms in the pathogenesis of vitiligo, strong evidence indicates involvement of cellular immunity in vitiligo. Destruction of melanocytes may be directly mediated by autoreactive CD8⁺ T cells. Activated CD8⁺ T cells have been demonstrated in perilesional vitiligo skin. In addition, melanocyte-specific T cells have been detected in peripheral blood of patients with autoimmune vitiligo.⁴

The following related eMedicine articles may be of interest:

• Hashimoto Thyroiditis
• Graves Disease
• Addison Disease
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Alopecia Areata
• Pernicious Anemia
• Inflammatory Bowel Disease
• Psoriasis
• Autoimmune Polyglandular Syndrome, Type 1

Additionally, for a Medscape CME course related to autoimmunity and medications, see Drug Insight: Autoimmune Effects of Medications: What's New?.

Intrinsic defect of melanocytes

Vitiligo melanocytes may have an intrinsic defect leading to melanocyte death. These melanocytes demonstrate various abnormalities, including abnormal, rough endoplasmic reticulum and incompetent synthesis and processing of melanocytes. In addition, homing-receptor dysregulation has also been detected. Early apoptosis of melanocytes has also been suggested as a cause of reduced melanocyte survival; however, subsequent investigation found that the relative apoptosis susceptibility of vitiligo melanocytes was comparable with that of normal control pigment cells.⁵

Disturbance in oxidant-antioxidant system in vitiligo

Oxidant stress may also play an essential role in the pathogenesis of vitiligo. Studies suggest that accumulation of free radicals toxic to melanocytes leads to their destruction. Because patients with vitiligo exhibit a characteristic yellow/green or bluish fluorescence in clinically affected skin, this led to the discovery that the fluorescence is due to accumulation of 2 different oxidized pteridines. The overproduction of pteridines led to the discovery of a metabolic defect in tetrahydrobiopterin homeostasis in patients with vitiligo, which results in the accumulation of melanocytotoxic hydrogen peroxide.⁶

Neural theory

Case reports describe patients afflicted with a nerve injury who also have vitiligo have hypopigmentation or depigmentation in denervated areas. Additionally, segmental vitiligo frequently occurs in a dermatomal pattern, which suggests that certain chemical mediators are released from nerve endings that affect melanin production. Further, sweating and vasoconstriction are increased in depigmented patches of vitiligo, implying an increase in adrenergic activity. Finally, increased urinary excretion of homovanillic acid and vanilmandelic acid (neurometabolites) has been documented in patients with vitiligo. This may be a secondary or primary phenomenon.⁷

In summary, although the ultimate cause of vitiligo is not completely known, this condition does not reflect simple melanocyte loss, but possible immunologic alterations and other molecular defects leading to pigment cell destruction; however, melanocytes may be present in depigmented skin after years of onset and may still respond to medical therapy under appropriate stimulation.

Genetics of vitiligo⁸

Vitiligo is characterized by incomplete penetrance, multiple susceptibility loci, and genetic heterogeneity. The inheritance of vitiligo may involve genes associated with the biosynthesis of melanin, a response to oxidative stress, and regulation of autoimmunity.⁹

Human leukocyte antigens (HLAs) may be associated, but not in a consistent manner. For example, HLA-DR4 is increased in blacks, HLA-B13 is increased in Moroccan Jews, and HLA-B35 is increased in Yemenite Jews. An association with HLA-B13 is described in the presence of antithyroid antibodies.

Frequency

United States

In the United States, the relative rate is 1%.

International

Vitiligo is relatively common, with a rate of 1-2%. Approximately 30% of cases occur with a familial clustering of cases.

Sex

A female preponderance has been reported, but it is not statistically significant and the discrepancy has been attributed to an increase in reporting of cosmetic concerns by female patients.

Age

Vitiligo may appear at any time from birth to senescence, although the onset is most commonly observed in persons aged 10-30 years.

• It rarely is seen in infancy or old age. Nearly all cases of vitiligo are acquired relatively early in life.
• The average age of onset is approximately 20 years. The age of onset is unlikely to vary between the sexes.
• Heightened concern about the appearance of the skin may contribute to an early awareness of the condition among females.

Clinical

History

The most common form of vitiligo is an amelanotic macule or patch surrounded by healthy skin. The  macules are chalk or milk-white in color, and lesions are well demarcated.

The lesions are not readily apparent in lightly pigmented individuals; however,  they are easily distinguishable with a Wood lamp examination.

Physical

Vitiligo manifests as acquired white or hypopigmented macules or patches. The lesions are usually well demarcated, and they are round, oval, or linear in shape. The borders may be convex.⁶ Lesions enlarge centrifugally over time at an unpredictable rate. Lesions range from millimeters to centimeters in size. Initial lesions occur most frequently on the hands, forearms, feet, and face, favoring a perioral and periocular distribution.

Vitiligo lesions may be localized or generalized, with the latter being more common than the former. Localized vitiligo is restricted to one general area with a segmental or quasidermatomal distribution. Generalized vitiligo implies more than one general area of involvement. In this situation, the macules are usually found on both sides of the trunk, either symmetrically or asymmetrically arrayed.

The most common sites of involvement are the face, neck, and scalp. Many of the most common sites of occurrence are areas subjected to repeated trauma, including the following:

• Bony prominences
• Extensor forearm
• Ventral wrists
• Dorsal hands
• Digital phalanges

Involvement of the mucous membranes is frequently observed in the setting of generalized vitiligo. Vitiligo often occurs around body orifices such as the lips, genitals, gingiva, areolas, and nipples.

Body hair (leukotrichia) in vitiliginous macules may be depigmented. Vitiligo of the scalp usually appears as a localized patch of white or gray hair, but total depigmentation of all scalp hair may occur. Scalp involvement is the most frequent, followed by involvement of the eyebrows, pubic hair, and axillary hair, respectively. Leukotrichia may indicate a poor prognosis in regard to repigmentation. Spontaneous repigmentation of depigmented hair in vitiligo does not occur.

Clinical variants

Trichrome vitiligo has an intermediate zone of hypochromia located between the achromic center and the peripheral unaffected skin. The natural evolution of the hypopigmented areas is progression to full depigmentation. This results in 3 shades of color—brown, tan, and white—in the same patient (see Media File 1).

Marginal inflammatory vitiligo results in a red, raised border, which is present from the onset of vitiligo (in rare cases) or which may appear several months or years after the initial onset. A mild pruritus may be present (see Media File 2). 

Quadrichrome vitiligo is another variant of vitiligo, which reflects the presence of a fourth color (ie, dark brown) at sites of perifollicular repigmentation. A case of pentachrome vitiligo with 5 shades of color has also been described.⁷

Blue vitiligo results in blue coloration of vitiligo macules. This type has been observed in a patient with postinflammatory hyperpigmentation who then developed vitiligo.

Koebner phenomenon is defined as the development of vitiligo in sites of specific trauma, such as a cut, burn, or abrasion. Minimum injury is required for Koebner phenomenon to occur.

Clinical classifications of vitiligo

The classification system is important because of the special significance assigned by some authorities to each type of vitiligo. The most widely used classification of vitiligo is localized, generalized, and universal types and is based on the distribution, as follows: 

• Localized
  • Focal: This type is characterized by one or more macules in one area, most commonly in the distribution of the trigeminal nerve.
  • Segmental: This type manifests as one or more macules in a dermatomal or quasidermatomal pattern. It occurs most commonly in children. More than half the patients with segmental vitiligo have patches of white hair or poliosis. This type of vitiligo is not associated with thyroid or other autoimmune disorders.
  • Mucosal: Mucous membranes alone are affected.
• Generalized
  • Acrofacial: Depigmentation occurs on the distal fingers and periorificial areas.
  • Vulgaris: This is characterized by scattered patches that are widely distributed.
  • Mixed: Acrofacial and vulgaris vitiligo occur in combination, or segmental and acrofacial vitiligo and/or vulgaris involvement are noted in combination.
• Universal: This is complete or nearly complete depigmentation. It is often associated with multiple endocrinopathy syndrome.

Classification by progression, prognosis, and treatment

When progression, prognosis, and treatment are considered, vitiligo can be classified into 2 major clinical types: segmental and nonsegmental.

• Segmental: This usually has an onset early in life and rapidly spreads in the affected area. The course of segmental vitiligo can arrest, and depigmented patches can persist unchanged for the life of the patient (see Media File 3).
• Nonsegmental: This type includes all types of vitiligo, except segmental vitiligo (see Media File 4).¹⁰

Causes

Theories regarding destruction of melanocytes include autoimmune mechanisms, cytotoxic mechanisms, intrinsic melanocyte defects, oxidant-antioxidant mechanisms, and neural mechanisms.

• Autoimmune and cytotoxic hypotheses: Aberration of immune surveillance results in melanocyte dysfunction or destruction.
• Neural hypothesis: A neurochemical mediator destroys melanocytes or inhibits melanin production.
• Oxidant-antioxidant mechanisms: An intermediate or metabolic product of melanin synthesis causes melanocyte destruction.
• Intrinsic defect of melanocytes: Melanocytes have an inherent abnormality that impedes their growth and differentiation in conditions that support normal melanocytes.

Because none of these theories alone is entirely satisfactory, some have suggested a composite hypothesis.

Differential Diagnoses

Other Problems to Be Considered

Vitiligo and ocular disease

The uveal tract and retinal pigment epithelium contain pigment cells. Choroidal abnormalities have been reported in up to 30% of patients, and iritis has been reported in approximately 5% of patients. Exophthalmos may occur in the setting of concomitant Graves disease. Uveitis is the most significant ocular abnormality associated with vitiligo. The most severe form of uveitis is seen in the Vogt-Koyanagi-Harada syndrome. This syndrome is characterized by vitiligo, uveitis, aseptic meningitis, dysacusis, tinnitus, poliosis, and alopecia.

Alezzandrini syndrome includes facial vitiligo, poliosis, deafness, and unilateral visual changes. The affected eye has decreased visual acuity and an atrophic iris.⁶

Although the color of the irides does not change in patients with vitiligo, depigmented areas in pigment epithelium and choroid occur in up to 40% of patients.

Vitiligo and autoimmune disorders

Vitiligo is frequently associated with disorders of autoimmune origin, with thyroid abnormalities being the most common. Vitiligo usually precedes the onset of thyroid dysfunction. Patients with autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy have an increased prevalence of vitiligo. In this genetic syndrome, autoantibodies cause destruction of endocrine cells.¹¹

Moreover, studies suggest that an association exists between a positive family history of vitiligo, autoimmune/endocrine diseases, leukotrichia, and an increased incidence of vitiligo in children. In addition, pediatric patients with a positive family history of vitiligo show an earlier age of disease onset.¹²

Vitiligo and auditory abnormalities¹³

Melanin may play a significant role in the establishment and/or maintenance of the structure and function of the auditory system and may modulate the transduction of the auditory stimuli by the inner ear.¹⁴ The membranous labyrinth of the inner ear contains melanocytes, and the heaviest pigmentation is present in the scala vestibuli. Because vitiligo affects all melanocytes, auditory disturbances may result. Several studies have described familial vitiligo associated with hearing abnormalities and hypoacusis in 16% of patients younger than 40 years who have vitiligo.¹⁴

Vitiligo and melanoma^15,16

Vitiligolike depigmentation can occur in patients with malignant melanoma and is believed to result from a T-cell–mediated reaction to antigenic melanoma cells and cross-reactivity to healthy melanocytes. Most patients with melanoma or with vitiligo develop antibodies to similar antigens that are present both on melanocytes and on melanoma cells. These findings support the hypothesis that the clinical link between the 2 diseases results from immune responses to antigens shared by normal and malignant pigment cells. Studies have demonstrated that a halo nevus, hypopigmentation, or depigmentation may occur in patients with melanoma. The depigmentation or hypopigmentation spreads centrifugally from the trunk to other parts of the body. The sites of depigmentation may be remote from the original site of melanoma. Although metastasis has most likely occurred in the majority of patients, active vitiligo in these patients may signal a longer survival time than expected.

Workup

Laboratory Studies

Although the diagnosis of vitiligo generally is made on the basis of clinical findings, biopsy is occasionally helpful for differentiating vitiligo from other hypopigmentary disorders.

Vitiligo may be associated with other autoimmune diseases, especially thyroid disease and diabetes mellitus. Other associated autoimmune diseases include pernicious anemia, Addison disease, and alopecia areata. Patients should be made aware of signs and symptoms that suggest the onset of hypothyroidism, diabetes, or other autoimmune disease. If signs or symptoms occur, appropriate tests should be performed.¹⁶  

• Thyrotropin testing is the most cost-effective screening test for thyroid disease. Antinuclear antibody screening is also helpful. A CBC count with indices helps rule out anemia.
• Clinicians should also consider investigating for serum antithyroglobulin and antithyroid peroxidase antibodies, particularly if thyroid involvement is suspected. Antithyroid peroxidase antibodies are regarded as a sensitive and specific marker of autoimmune thyroid antibodies. Screening for diabetes can be accomplished with fasting blood glucose or glycosylated hemoglobin testing.

Other Tests

Vitiligo is diagnosed by means of inspection with a Wood lamp.

Histologic Findings

Microscopic examination of involved skin shows a complete absence of melanocytes in association with a total loss of epidermal pigmentation. Superficial perivascular and perifollicular lymphocytic infiltrates may be observed at the margin of vitiliginous lesions, consistent with a cell-mediated process destroying melanocytes. Degenerative changes have been documented in keratinocytes and melanocytes in both the border lesions and adjacent skin. Other documented changes include increased numbers of Langerhans cells, epidermal vacuolization, and thickening of the basement membrane. Loss of pigment and melanocytes in the epidermis is highlighted by Fontana-Masson staining and immunohistochemistry testing.^17,18

Treatment

Medical Care

No single therapy for vitiligo produces predictably good results in all patients; the response to therapy is highly variable. Treatment must be individualized, and patients should be made aware of the risks associated with therapy. During medical therapy, pigment cells arise and proliferate from the following 3 sources:

• The pilosebaceous unit, which provides the highest number of cells, migrating from the external root sheath toward the epidermis
• Spared epidermal melanocytes not affected during depigmentation¹⁹
• The border of lesions, migrating up to 2-4 mm from the edge

Systemic phototherapy

Systemic phototherapy induces cosmetically satisfactory repigmentation in up to 70% of patients with early or localized disease.¹⁶

Narrow-band UV-B phototherapy is widely used and produces good clinical results. Narrow-band fluorescent tubes (Philips TL-01/100W) with an emission spectrum of 310-315 nm and a maximum wavelength of 311 nm are used. Treatment frequency is 2-3 times weekly, but never on consecutive days. This treatment can be safely used in children, pregnant women, and lactating women. Short-term adverse effects include pruritus and xerosis. Several studies have demonstrated the effectiveness of narrow-band UV-B therapy as monotherapy.

UV-B narrow-band microphototherapy²⁰ is therapy targeting the specific small lesions. Selective narrow-band UV-B (311 nm) is used with a fiber optic system to direct radiation to specific areas of skin. Narrow-band UV-B has become the first choice of therapy for adults and children with generalized vitiligo.

Psoralen photochemotherapy involves the use of psoralens combined with UV-A light. Treatment with 8-methoxypsoralen, 5-methoxypsoralen, and trimethylpsoralen plus UV-A (PUVA) has often been the most practical choice for treatment, especially in patients with skin types IV-VI who have widespread vitiligo. Psoralens can be applied either topically or orally, followed by exposure to artificial UV light or natural sunlight. Vitiligo on the back of the hands and feet is highly resistant to therapy. 

The best results from PUVA can be obtained on the face, trunk, and proximal parts of the extremities. However, 2-3 treatments per week for many months are required before repigmentation from perifollicular openings merges to produce confluent repigmentation. The total number of PUVA treatments required is 50-300. Repigmentation occurs in a perifollicular pattern.

The advantages of narrow-band UV-B over PUVA include shorter treatment times, no drug costs, no adverse GI effects (eg, nausea), and no need for subsequent photoprotection.

Laser therapy

Another innovation is therapy with an excimer laser, which produces monochromatic rays at 308 nm to treat limited, stable patches of vitiligo. This new treatment is an efficacious, safe, and well-tolerated treatment for vitiligo when limited to less than 30% of the body surface. However, therapy is expensive. Localized lesions of vitiligo are treated twice weekly for an average of 24-48 sessions.

According to studies from 2004 and 2007, combination treatment with 0.1% tacrolimus ointment plus the 308-nm excimer laser is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions.^21,22

Steroid therapy

Systemic steroids (prednisone) have been used, although prolonged use and their toxicity are undesirable.²³ Steroids have been reported anecdotally to achieve success when given in pulse doses or low doses to minimize adverse effects. The benefits versus the toxicity of this therapy must be weighed carefully. More research is necessary to establish the safety and effectiveness of this therapy for vitiligo.

A topical steroid preparation is often chosen first to treat localized vitiligo because it is easy and convenient for both doctors and patients to maintain the treatment. The results of therapy have been reported as moderately successful, particularly in patients with localized vitiligo and/or an inflammatory component to their vitiligo, even if the inflammation is subclinical.

In general, intralesional corticosteroids should be avoided because of the pain associated with injection and the risk of cutaneous atrophy.

Topical therapies

The combination of topical calcipotriene and narrow-band UV-B or PUVA results in improvement appreciably better than that achieved with monotherapy.

Depigmentation therapy

If vitiligo is widespread and attempts at repigmentation do not produce satisfactory results, depigmentation may be attempted in selected patients.

The long-term social and emotional consequences of depigmentation must be considered. Depigmentation should not be attempted unless the patient fully understands that the procedure generally results in permanent depigmentation. Some authorities have recommended consultation with a mental health professional to discuss potential social consequences of depigmentation.

A 20% cream of monobenzylether of hydroquinone is applied twice daily for 3-12 months. Burning or itching may occur. Allergic contact dermatitis may be seen.²⁶

Topical PUVA is of benefit in some patients with localized lesions. Cream and solution of 8-methoxypsoralen (0.1-0.3% concentration) are available for this treatment.⁶ It is applied 30 minutes prior to UV-A radiation (usually 0.1-0.3 J/cm² UV-A) exposure. It should be applied once or twice a week. Physicians who prescribe PUVA therapy should be thoroughly familiar with the risks associated with the treatment. Additional UV-A exposure should be avoided while skin is sensitized because severe burns may occur if patients receive additional UV-A exposure. Sunscreens should be given to all patients with vitiligo to minimize risk of sunburn or repeated solar damage to depigmented skin. Patients must understand that most sunblocks have a limited ability to screen UV-A light.

Of general concern, tanning of surrounding normal skin exaggerates the appearance of vitiligo, and this is prevented by sun protection. Sunscreens with a sun protection factor of 15 or higher are best.

Surgical Care

Surgical alternatives exist for the treatment of vitiligo; however, because of the time-consuming nature of surgical therapies, these treatment regimens are limited to segmental or localized vitiligo. Unilateral (segmental) vitiligo has been shown as the most stable form, responding well to surgical interventions in numerous studies. Such areas as dorsal fingers, ankles, forehead, and hairline tend to not repigment well. Patients who have small areas of vitiligo with stable activity are candidates for surgical transplants. The most important factors indicating stability are as follows:

• No progression of lesions for at least 2 years
• Spontaneous repigmentation indicates vitiligo inactivity
• A positive minigrafting test disclosing repigmentation at 4-5 minigrafts, which, to date, is the most accurate evidence of vitiligo stability
• Absence of new koebnerization, including the donor site for the minigrafting test
• Unilateral vitiligo most stable form of vitiligo²⁷  

Five basic methods for repigmentation surgery have been described, as follows^28,29 :

• Noncultured epidermal suspensions: After the achromic epidermis is removed, an epidermal suspension with melanocytes and keratinocytes previously prepared by trypsinization of normally pigmented donor skin is spread onto the denuded area and immediately covered with nonadherent dressings.
• Thin dermoepidermal grafts: The depigmented epidermis is removed by superficial dermabrasion, including the papillary dermis, and very thin dermoepidermal sheets harvested with dermatome are grafted onto the denuded skin.
• Suction epidermal grafting: Epidermal grafts can be obtained by vacuum suction, usually with 150 mm Hg. The recipient site can be prepared by suction, freezing, or dermabrasion of the sites 24 hours before grafting. The depigmented blister roof is discarded, and the epidermal donor graft is placed on the vitiliginous areas.
• Punch minigrafting: Small donor grafts are inserted into the incision of recipient sites and held in place by a pressure dressing. The graft heals readily and begins to show repigmentation within 4-6 weeks. Some pebbling persists but is minimal, and the cosmetic result is excellent.
• Cultured epidermis with melanocytes or cultured melanocyte suspensions: Depigmented skin is removed using liquid nitrogen, superficial dermabrasion, thermosurgery, or carbon dioxide lasers; very thin sheets of cultured epidermis are grafted or suspensions are spread onto the denuded surface.²⁷

Micropigmentation³⁰ is another option. Tattooing can be used to repigment depigmented skin in dark-skinned individuals. Color matching is difficult, and the color tends to fade. Skin can be dyed with dihydroxyacetone preparations, although the color match is often poor.

Consultations

Consultation with an ophthalmologist is warranted. Additionally, psychological needs must be addressed on a continual basis with appropriate referrals to mental health specialists.⁷

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Corticosteroids

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. These drugs are used to stop spread of vitiligo and accomplish repigmentation. Data supporting the efficacy of such treatment is largely anecdotal. More study is needed to establish the safety and efficacy of systemic agents.

Topical steroids: triamcinolone 0.1% ointment or cream (Aristocort), hydrocortisone 2.5 % ointment, clobetasol ointment or cream (Clobex)

For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Intramuscular injection may be used for widespread skin disorder, or intralesional injections may be used for localized skin disorder. Moderately high potency; available as ointment (0.1%) or cream (0.5%).

Dosing

Adult

Apply a thin film qd; more frequent applications may be required, especially in areas where preparation tends to be removed before absorption is complete

Pediatric

Apply as in adults

Interactions

Coadministration with barbiturates, phenytoin, and rifampin decreases effects of triamcinolone

Contraindications

Documented hypersensitivity; fungal, viral, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use in decreased skin circulation; prolonged use, applications over large areas, and use of potent steroids and occlusive dressings may result in systemic absorption; systemic absorption may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria

Psoralens

These agents are used with UV-A exposure for the treatment of localized or generalized vitiligo.

Methoxsalen (8-MOP, Oxsoralen)

Inhibits mitosis by covalently binding to pyrimidine bases in DNA when photoactivated by UV-A. Effective in treating hyperkeratosis.

Dosing

Adult

PO: 0.3-0.4 mg/kg PO with food 1.5 h before UV-A exposure once or twice weekly; alternatively, 0.57 mg/kg 1.5-2 h before UV exposure; at least 48 h apart
Topically: 0.1% ointment; apply 30 min before controlled UV-A exposure once or twice weekly

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamide

Contraindications

Documented hypersensitivity; squamous cell cancer; cataracts; light-sensitive diseases (eg, lupus, porphyria); ingestion of photosensitizing drugs; hepatic disease; arsenic therapy; noncompliance or unwillingness to use protective glasses after treatment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use with UV-A causes photoaging of skin; phototoxic reactions possible; caution with hepatic insufficiency; eye protection necessary during and after therapy; use only if response to other therapy is inadequate; long-term use may increase risk of skin cancer

Trioxsalen (Trisoralen)

For treatment of hyperkeratosis. In UV-A radiation, inhibits mitosis by covalently binding to pyrimidine bases in DNA.

Dosing

Adult

0.6-0.8 mg/kg PO with food 1.5 h prior to UV-A exposure once or twice weekly; alternatively, 10 mg/d once 2-4 h before controlled exposure to UV-A or sunlight; not to exceed 14 d

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; a history of melanoma, acute lupus erythematosus, or porphyria; inability to comply with instructions regarding UV-A exposure and eye protection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use with UV-A causes photoaging of skin; severe burns may occur from sunlight or UV-A exposure if dose or frequency is exceeded; caution with hepatic insufficiency

Calcipotriene (Dovonex)

Dosing

Adult

Apply to affected areas bid (qam, qhs, and after washing); apply thin film, avoiding eyes and lips; do not cover with occlusive dressing.

Pediatric

Not recommended

Interactions

Substances that stimulate absorption should not be administered concomitantly because of potential effects on calcium metabolism

Contraindications

Systemic treatment of calcium deficiency; kidney or liver dysfunction; hypercalcemia or calcium metabolism problems

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Breastfeeding not advised during treatment; low incidence of temporary skin irritation (reddening, itching); temporarily or permanently discontinue or decrease frequency if sensitivity or severe irritation; in clinical studies, no hypercalcemia observed at maximal dose of 30 g/d

Immunomodulator

Tacrolimus (Protopic) ointment 0.03% or 0.1%

Dosing

Adult

Apply to the affected area twice daily; continue for 1 wk after signs and symptoms resolve. Avoid occlusive dressings

Pediatric

Protopic 0.03% only: Apply as in adults

Interactions

Formal studies not conducted; because of minimal absorption, interactions with systemic drugs are unlikely but cannot be excluded; caution with concomitant administration of known CYP3A4 inhibitors (eg, erythromycin, itraconazole, ketoconazole, calcium channel blockers, cimetidine) in patients with widespread and/or erythrodermic disease

Contraindications

Ulcerous skin lesions and erosion forming marked plaque; severe renal impairment or hyperkalemia (may aggravate renal impairment or hyperkalemia); pregnant or possibly pregnant patients; history of hypersensitivity to any ingredient; patients receiving UV therapy, such as PUVA; Netherton syndrome (high possibility of increased systemic absorption)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Clinical infection should be resolved first; in patients with atopic dermatitis exposed to superficial skin infection (eg, dermatitis eczema, Kaposi varicelliform eruption), might increase risk of varicella-zoster infection (herpes zoster), dermatitis viral infection, or eczema herpeticum (balance risks and benefits); lymph node symptoms reported (mostly related to skin infection), notably in transplantation patients taking immunosuppressants (eg, whole-body tacrolimus); if cause of lymph node symptoms not found or if monocyte symptoms present, consider discontinuation; patients should avoid UV exposure; burning or tingling pain or itching, most frequently during first few days, resolves with improvement of atopic dermatitis

Miscellaneous

Medicolegal Pitfalls

• Physicians who prescribe PUVA therapy should be thoroughly familiar with the risks of burns, cataract formation, and carcinogenesis associated with treatment.
• Patients should be made aware of signs and symptoms that suggest the onset of hypothyroidism, diabetes, or other autoimmune diseases. If signs or symptoms occur, appropriate tests should be performed.
• Treatment must be individualized, and patients should be made aware of the risks associated with therapy.

Multimedia

Media file 1: Trichrome vitiligo.

Media file 2: Marginal inflammatory vitiligo.

Media file 3: Segmental vitiligo.

Media file 4: Nonsegmental vitiligo.

References

1. Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun. 2008;10:227-43. [Medline].

2. Toussaint S, Kamino H. Noninfectous papular and squamous diseases. In: Elder D, Elenitas R, Jaworsky D, Johnson B Jr. Lever's Histopathology of the Skin. Philadelphia, Pa: Lippincot-Raven; 1997:154-5.

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Keywords

vitiligo, hypopigmentation, white spot disease, acquired leukoderma, nonpigmented skin, depigmented skin, depigmentation, loss of melanin, hypomelanosis, HLA-DR4, HLA-B13, HLA-B35, leukotrichia, trichrome vitiligo, blue vitiligo

Contributor Information and Disclosures

Author

Vlada Groysman, MD, Staff Physician, Department of Dermatology, University of Alabama School of Medicine
Vlada Groysman, MD is a member of the following medical societies: American Academy of Dermatology, Medical Dermatology Society, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Naveed Sami, MD, FAAD, Assistant Professor Department of Dermatology, University of Alabama School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Mark G Lebwohl, MD, Chairman, Department of Dermatology, Mount Sinai School of Medicine
Mark G Lebwohl, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Abbott Laboratories Honoraria Consulting; Actelion Honoraria Consulting; Amgen Honoraria Consulting; Astellas Honoraria Consulting; Centocor Honoraria Consulting; DermiPsor Honoraria Consulting; Galderma  Consulting; Genentech Honoraria Consulting; Helix BioMedix Honoraria Consulting; Medicis Honoraria Investigator

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Seung-Kyung Hann, MD, to the development and writing of this article.

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