Chapter 74. Vitiligo

The prevalence of vitiligo is reasonably consistent among different populations: ∼0.38% in Caucasians,1 0.34% in Afro-Caribbeans,2 0.46% in Indians,3 though perhaps somewhat less frequent in Han Chinese, 0.093%.4 Vitiligo appears to affect both genders equally, though women are overrepresented among patients seeking clinical care. Vitiligo can develop at any age,5 with a mean age-of-onset in Caucasian patients of about 24 years.6 The most common subtype, generalized vitiligo (GV), is an autoimmune disease that is associated with other autoimmune diseases in about 20%–30% of patients, most frequently autoimmune thyroid disease (Hashimoto's thyroiditis or Grave's disease), rheumatoid arthritis, psoriasis, type 1 diabetes (usually adult-onset), pernicious anemia, systemic lupus erythematosus, and Addison's disease.7

Vitiligo is a multifactorial, polygenic disorder, with a complex pathogenesis that is not yet well understood.8 Of various theories of disease pathogenesis, the most accepted is that genetic and nongenetic factors interact to influence melanocyte function and survival, eventually leading to autoimmune destruction of melanocytes.7 Other suggested explanations have included defects of melanocyte adhesion,9 neurogenic damage,10 biochemical damage,11 autocytotoxicity,12 and others.

Genetics of Vitiligo

Large-scale epidemiological surveys have shown that most cases of vitiligo occur sporadically, although about 15%–20% of patients have one or more affected first-degree relatives. Typically, familial aggregation of cases exhibits a non-Mendelian pattern suggestive of polygenic, multifactorial inheritance.8 Concordance in monozygotic twins is 23%,6 indicating that both genetic and nongenetic (presumably environmental) factors play major roles in disease pathogenesis.

Almost all studies of vitiligo genetics have focused on GV. Several genes involved in immune function, including loci in the MHC, CTLA4, PTPN22, IL10, MBL2, and NALP1 (NLRP1), have been implicated in susceptibility to GV on the basis of genetic linkage or association studies.7 A recent, very large genome-wide association (GWA) study of European Caucasian GV patients and families identified at least ten different loci that contribute to GV risk.13 Seven of these GV susceptibility loci have also been associated with other autoimmune diseases [(1) HLA class I, (2) HLA class II, (3) PTPN22, (4) LPP, (5) IL2RA, (6) UBASH3A, and (7) C1QTNF6], two loci encode proteins involved in immune function [(1) RERE and (2) GZMB], and another locus, TYR, encodes tyrosinase, a key enzyme of melanin biosynthesis and the major GV autoantigen.

Segmental vitiligo (SV) appears to be genetically distinct from GV. Its generally sporadic occurrence and unilateral distribution have led to the suggestion that it might result from somatic mosaicism for de novo mutations,14,15 perhaps in genes that are critical for melanoblast/melanocyte development or survival, although this hypothesis remains to be confirmed.

Autoimmune Hypothesis

There is compelling biological evidence supporting an autoimmune basis for GV.16 GV is epidemiologically associated with a number of other autoimmune diseases,6,17 both in patients and in their close relatives, indicative of a heritable autoimmune diathesis. Humoral immunity was first implicated by the finding in some cases of circulating antimelanocyte autoantibodies18 that target various melanocyte antigens, including tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, and others, and that have the capability to kill melanocytes in vitro19 and in vivo.20 Currently, these autoantibodies are thought to reflect secondary humoral responses to melanocyte destruction rather than a primary cause of GV.18 A greater role is attributed to the inflammatory infiltrate sometimes seen at the margins of active GV lesions, composed mainly of cytotoxic T lymphocytes. As these T cells express a type-1 cytokine profile and colocalize with epidermal melanocytes, it has been hypothesized that these cells are actively cytolytic toward remaining melanocytes, via the granzyme/perforin pathway.21

An immune mechanism has also been suggested to underlie chemical leukoderma.22 The so-called “occupational vitiligo” may occur in individuals who encounter large doses of phenolic compounds, usually 4-tertiary butyl phenol (4-TBP) and other phenolic compounds that may be contained in cleaning solutions. Occupational vitiligo usually initially involves the hands and forearms (the site of contact with the inciting agent). At present, it is unclear whether these agents are directly toxic to melanocytes, or whether some individuals might be genetically susceptible to melanocyte injury from aliphatic phenolic derivatives, ultimately resulting in melanocyte death, release of antigenic intracellular proteins, loss of tolerance, and autoimmunity.

An immune mechanism has also been proposed for the vitiligo-like depigmentation, which can appear in the course of IL-2 immunotherapy-based treatments for cutaneous melanoma, possibly via the stimulatory effect of IL-2 on T cell growth and activation.23–25 Some melanoma-associated antigens (e.g., MART-1, gp100, and tyrosinase) are expressed on normal melanocytes, suggesting that the occurrence of treatment-related vitiligo-like depigmentation in melanoma may involve cross-reaction of some antimelanoma immune responses with normal melanocytes.

There is some evidence that vitiligo is a disease of the entire epidermis, possibly involving biochemical abnormalities of both melanocytes and keratinocytes.11 The specific morphological and functional abnormalities observed in vitiligo melanocytes and keratinocytes are thought to have a genetic background.11 Ultrastructural abnormalities of keratinocytes from perilesional vitiligo skin have been related to impaired mitochondrial activity,26 and are thought to affect the production of specific melanocyte growth factors and cytokines that regulate melanocyte survival.11 An essential biochemical finding is elevated levels of H2O2 in affected regions of epidermis,27 that may be caused in part by reduced enzymatic antioxidant capacity of keratinocytes and melanocytes.11,19 A defective antioxidant defense may confer melanocytes an increased susceptibility both to immunologic cytotoxicity and to cytotoxicity induced by reactive oxygen species.19

The principal clinical manifestation of vitiligo is the appearance of acquired milk-white macules with fairly homogeneous depigmentation and well-defined borders. On the basis of the polymorphic distribution, extension, and number of white patches, vitiligo is classified into generalized (vulgaris, acrofacial, mixed), universalis, and localized (focal, segmental, and mucosal) types.28 Vitiligo is also classified as segmental and nonsegmental types, on the basis of distinctive clinical features and natural histories.29 According to this classification, non-SV includes all cases not classified as segmental, including localized, generalized, and acrofacial.

• Vitiligo vulgaris—multiple scattered lesions distributed in a more or less symmetrical pattern; the most common presentation of GV (Fig. 74-1).
• Acrofacial vitiligo—affects the distal end of fingers and facial orifices in a circumferential pattern; a subtype of GV (Fig. 74-2).
• Mixed vitiligo—combination of acrofacial and vulgaris, or segmental and acrofacial types.
• Vitiligo universalis—complete or nearly complete depigmentation of the whole body (Fig. 74-3); the most severe form of GV.
• Focal vitiligo—characterized by the presence of one/few macule(s) in one area but not distributed in a segmental pattern (Fig. 74-4); considered a precursor form of GV.
• Mucosal vitiligo—a term reserved for depigmentation of mucous membrane alone.
• SV—characterized by macules having unilateral dermatomal distribution that do not cross the midline (Fig. 74-5). It generally affects young children and typically remains localized, the depigmented lesions persisting unchanged for many years.30 The occurrence of concomitant other autoimmune diseases is uncommon, compared with GV.29,31,32

Vitiligo often demonstrates a predilection for sun-exposed regions, body folds, and periorificial areas, although any part of the body can be affected. Various precipitating factors have been suggested, including physical trauma to the skin, sunburn, psychological stress, inflammation, pregnancy, contraceptives, vitamin deficiency, and many others. However, at this time no specific environmental triggers have been proven.

Vitiligo may appear at sites of skin trauma (Koebner's phenomenon) (Fig. 74-6).

Leukotrichia (depigmentation of hair within vitiligo macules (Fig. 74-7), can be quite variable (10%–60%), and is considered to indicate destruction of the melanocyte reservoir within the hair follicle, therefore, predicting a poor therapeutic response.28 Premature graying of the hair has been described in up to 37% of patients with vitiligo,28 although poor definition and quantitation of this feature makes this supposed clinical association uncertain.

• Trichrome vitiligo is characterized by the presence of patches of intermediate hue (hypopigmentation) between the normal skin and the completely depigmented skin.
• Quadrichrome vitiligo is characterized by the presence of a fourth color (dark brown) at sites of perifollicular repigmentation. It is more often encountered in patients with darker skin phototypes.
• Pentachrome vitiligo—the occurrence of five shades of color: (1) white, (2) tan, (3) medium brown, (4) dark brown, and (5) black.
• Confetti vitiligo or vitiligo ponctué—tiny punctate-like depigmented macules on a hyperpigmented macule or on normal skin.
• Red vitiligo—the depigmented lesions have a raised erythematous border.
• Blue vitiligo—a blue–gray appearance of the skin, which corresponds histologically with the absence of epidermal melanocytes and presence of numerous dermal melanophages.

Comorbid Associations

GV has been often associated with a variety of other conditions, principally autoimmune diseases.33 The most prevalent associated autoimmune disease is autoimmune thyroid dysfunction, either hypothyroidism (Hashimoto's thyroiditis) or hyperthyroidism (Grave's disease). Other autoimmune diseases such as rheumatoid arthritis, psoriasis, type 1 diabetes mellitus (usually adult-onset), pernicious anemia, systemic lupus erythematosus, and Addison's disease also occur with increased frequency in patients with GV.6,17 Most of these disorders, including GV, can occur in various combinations and constitute components of the APECED (APS1) and Schmidt (APS2) multiple autoimmune disease syndromes.

Vitiligo can also be part of the Vogt–Koyanagi–Harada (VKH) syndrome, a multiorgan disorder that affects pigmented structures, such as the eye, inner ear, meninges, and skin.34 Several clinical and experimental studies have pointed to a role of cell-mediated immunity in VKH, particularly involving CD4+ T cells and Th1 cytokines.35,36

Another very rare multiorgan disorder, Alezzandrini syndrome, associates facial skin depigmentation, poliosis, deafness, and unilateral tapetoretinal degeneration of the eye.37 However, many investigators now believe that VKH and Alezzandrini's syndrome are merely different clinical expressions of the same fundamental disease.38

Depigmentation Other Than Vitiligo

Skin depigmentation may occur in melanoma patients in three different clinical contexts39: partial depigmentation (“regression”) of the tumor, leukoderma acquisitum centrifugum around the tumor, and vitiligo-like depigmentation, occurring at distant sites. Vitiligo-like depigmentation is thought to be a marker of the patient developing immunity against melanoma cells and to be an indicator of favorable prognosis, especially in advanced stages.25

The most common form of leukoderma acquisitum centrifugum appears around pigmented nevi (called halo nevi), and often progress to spontaneous disappearance of the nevus,39 presumably via lymphocyte-mediated destruction of nevus cells.

Diagnosis

The diagnosis of vitiligo is established principally on clinical grounds, which may include distribution and extent of lesions, and natural history of disease.40

Laboratory

Given the association between vitiligo and other autoimmune diseases, several screening laboratory tests are helpful, including T4 and thyroid-stimulating hormone levels, antinuclear antibodies, and complete blood count. Clinicians should also consider testing for serum antithyroglobulin and antithyroid peroxidase antibodies, particularly when patients have signs and symptoms suggestive of thyroid disease.

Histology

A skin biopsy is rarely necessary to confirm the diagnosis of vitiligo. Generally, histology shows an epidermis devoid of melanocytes in lesional areas,41 and sometimes sparse dermal, perivascular, and perifollicular lymphocytic infiltrates at the margins of early vitiligo lesions and active lesions, consistent with cell-mediated immune processes destroying melanocytes in situ.42 Some reports42 have suggested that melanocytes may never be completely absent from the depigmented epidermis and that residual melanocytes maintain the capability of recovering functionality. Further studies are needed to clarify this highly debated issue with obvious therapeutic implications.

Differential diagnosis for vitiligo is presented in Box 74-1 and Box 74-2.43,44

The clinical course of any given case of GV is unpredictable, but is typically gradually progressive and difficult to control with therapy. Sometimes lesions spread over time, whereas in other cases disease activity stops, persisting in stable status for a long period. Some clinical parameters such as a long duration of the disease, occurrence of Koebner's phenomenon, leukotrichia, and mucosal involvement have been suggested as indicators of relatively poor prognosis.28

Fundaments of Vitiligo Therapy: Melanocyte Repopulation

The key principle of vitiligo therapy is facilitating repopulation of depigmented patches of the interfollicular epidermis with active melanocytes that are able to migrate, survive to repopulate the depigmented skin, and carry out melanin biosynthesis.45 Repigmentation may occur spontaneously and may also be therapy-induced. Spontaneous repigmentation is unpredictable, often clinically insignificant, and tends to be cosmetically unacceptable.46,47 It occurs in fewer than 50% of patients, most commonly in younger patients and in sun-exposed areas, where natural sunlight may act as an inducing agent.48 In clinical practice, the most frequently encountered pattern of repigmentation is perifollicular (Fig. 74-8), though other patterns, such as marginal, diffuse, or combined also may occur.

The principal source of melanocytes involved in repopulation of vitiligo skin is most likely melanocyte precursors derived from the outer root sheath (ORS) or bulge area of the hair follicle.49–51 A secondary potential reservoir may be located near lesional borders. The middle and lower parts of the ORS are populated by l-3,4-dihydroxyphenylalanine (DOPA)-negative, amelanotic melanocytes,49,50 which may be recruited from the ORS of the hair follicle in response to ultraviolet (UV), corticosteroids, or other stimuli. As a result, the number of melanocytes in the ORS of hair follicles increases significantly and some become active, suggesting that melanocyte precursors proliferate and at least some undergo maturation.50 Activated ORS melanocytes acquire all of the structural and enzymatic proteins required for melanogenesis, proliferation and maturation as they migrate up the hair follicle into the nearby epidermis, where they spread centrifugally and form perifollicular pigment islands. They then become larger cells, with intense DOPA oxidase activity.

Vitiligo repigmentation is assessed in terms of the proportion of treated subjects in whom a specified degree of repigmentation is achieved; depending on the study, more than 50% or more than 75% repigmentation may be considered a good response.52 Wood's lamp (UVA) examination is useful to monitor response to therapy. In the absence of epidermal melanin that otherwise absorbs most of the UVA light, more photons reach the dermis, where they are absorbed by collagen that then fluoresces and emits bright visible light. In contrast, visible wavelengths of ambient room light are less well absorbed by melanin in the normally pigmented epidermis than UVA wavelengths and do not produce fluorescence in the dermis. Hence, under Wood's light the vitiligo area appears brighter and the normal skin appears darker than when illuminated with ambient room light (Fig. 74-9).

Therapeutic Approaches

Different treatment strategies (Box 74-3) have been designed to inhibit the immune response in vitiligo, thereby reducing melanocyte destruction, and also enhancing epidermal repopulation by melanocytes, both by stimulating recovery of damaged melanocytes in situ and by reactivating residual melanocytes or stimulating melanocyte in-migration from neighboring skin or hair follicles. However, at present it is not clearly understood to what extent treatments must suppress the autoimmune process versus stimulate melanocyte repopulation of the epidermis to provide maximum efficacy.

UV radiation therapy includes phototherapy with narrowband UVB (NB-UVB—311 nm) or broadband UVB (BB-UVB—290–320 nm), and photochemotherapy. UV therapy is thought to act as a skin immunomodulator, regulating the activity of inflammatory cytokines, depleting of Langerhans cells, modulating the activity of regulatory T cells, and polarizing the immune response toward the Th2 profile, thereby reducing or stabilizing the depigmentation process in vitiligo.45 In addition, UV radiation coordinates several of the pathways via which melanogenic cytokines stimulate melanogenesis.45 Furthermore, UV may also induce the release of epidermal factors that stimulate melanocyte proliferation and migration, although this speculation has not been substantiated in repigmenting vitiligo lesions. The release of several paracrine factors produced by UV-exposed keratinocytes53 that regulate melanocyte functions is thought to be under p53 regulation,54 although further studies are needed.

Ultraviolet B Narrowband

Narrowband UV (NB-UVB) light, with peak emission at 311 nm, is considered the most effective and safest current therapy for vitiligo, and thus is currently the treatment of choice for patients with moderate-to-severe GV. Recent studies evaluating psoralen and UVA (PUVA) versus NB-UVB indicate that NB-UVB produces higher repigmentation rates and better color matching).55 NB-UVB has fewer short-term adverse reactions such as painful erythema and appears to have fewer long-term side effects such as epidermal thickening, atrophy, and photocarcinogenesis than PUVA.56 Several clinical studies have reported high rates (≥75%) of repigmentation in at least 40% of patients treated with NB-UVB.57–60

The most commonly used NB-UVB protocol43 involves twice-weekly administration of a fixed starting dose of 0.21 J/cm2, increasing the dose by 20% at each session until the minimal erythema dose (the lowest dose that results in visible erythema on depigmented skin at 24 hours) has been reached. Approximately 9 months of therapy are required to achieve maximal repigmentation; at least 3 months of treatment are warranted before the condition can be classified as nonresponsive.

The most responsive sites are face, trunk, and limbs, and the least responsive sites are the hands and feet.

Photochemotherapy (PUVA)

Until recently, PUVA was considered the mainstay of therapy for patients with widespread vitiligo. PUVA consists of a combination of topical or oral 8-methoxypsoralen with UVA (320–400 nm) irradiation. The psoralen of choice, methoxsalen, is given in an oral dose of 0.4-mg/kg body weight, 1–2 hours prior to UVA exposure. For topical PUVA therapy, methoxsalen 0.1% is applied to areas of vitiligo 30–60 minutes before exposure to UV radiation. Topical PUVA is indicated in patients whose vitiligo involves less than 20% of the body surface area, and painful burns (phototoxicity reactions) are unfortunately difficult to avoid. Oral psoralens can be used for patients with more extensive involvement or in patients who do not respond to topical PUVA (see Chapter 237). After oral treatment, patients must wear UVA-blocking glasses, and it is also recommended they use broad-spectrum sunscreens and wear protective clothing. Patients with darker complexions tend to respond best to PUVA, possibly because they tolerate higher PUVA exposures.61 Potential side effects of PUVA therapy are discussed in Chapter 237. PUVA is not recommended for use in children under the age of 12 years owing to the long-term delayed risks of cataract formation and skin cancer.

Topical Corticosteroids

Topical corticosteroids represent the first-line therapy for localized vitiligo, and are highly recommended for facial or small lesions and for use in children. Advantages include ease of application, high compliance rate, and low cost. Compared with PUVA, which promotes a predominantly perifollicular pattern of repigmentation, topical corticosteroids result in more diffuse repigmentation, which occurs more quickly but is less stable.62 Light and electron microscopy of skin biopsies from control and steroid-treated areas showed marked repopulation by functional melanocytes in the repigmented vitiliginous skin. In steroid repigmented areas melanocytes appeared dendritic and DOPA-positive, and unlike melanocytes in the pigment margins of untreated areas of vitiligo, contain many melanosomes of normal size and shape.63 The current trend, based on the results of a large meta-analysis that included randomized controlled trials of 29 patient series, is that class 3 and 4 corticosteroids are the most effective for treatment for localized vitiligo.52 Thus, localized lesions can be treated with a high-potency fluorinated corticosteroid (e.g., clobetasol propionate ointment, 0.05%) for 1–2 months. Treatment can be gradually tapered to a lower potency corticosteroid (e.g., hydrocortisone butyrate cream, 0.1%). Caution is necessary when using topical steroids on and around the eyelids, as their use can increase intraocular pressure and exacerbate glaucoma. Vitiligo recurrence after cessation of treatment and corticosteroid-induced side effects (i.e., skin atrophy, telangiectases, striae, and, rarely, contact dermatitis) are the limiting factors. Combination therapy (corticosteroids + UVB, corticosteroids + calcineurin inhibitors, corticosteroids + vitamin D analogs) may be beneficial in some cases, as two agents together may act synergistically on pigment restoration and on immune suppression, at lower individual doses, thus, potentially minimizing overall side effects.

Systemic Corticosteroids

Systemic corticosteroids have been used in pulse therapy and for short periods to halt rapid spread of depigmentation in some cases of GV.61

Calcineurin Inhibitors

Calcineurin inhibitors can be effective in vitiligo therapy because of their capacity to restore the altered cytokine network. Tacrolimus has been shown to inhibit T cell activation by downregulating transcription of genes encoding proinflammatory cytokines IL-2, IL-3, IL-4, IL-5, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in T cells.64 In addition, a direct effect of tacrolimus on melanocyte growth and migration during repigmentation has been reported.65 Topical calcineurin inhibitors (e.g., tacrolimus ointment 0.03%–0.1%, pimecrolimus ointment 1%) are generally preferred for treating localized vitiligo lesions of the face and neck,43 and seem to be more effective in combination with UV radiation delivered by high-fluency UVB devices.43 Although several reports have emphasized the advantages of calcineurin inhibitors (selective mode of action, absence of skin atrophy, and systemic absorption), additional studies of their effectiveness are needed, as well as more information about possible risks of cutaneous and extracutaneous cancers.

Topical Vitamin D Derivatives

Vitamin D analogs—calcipotriol ointment (0.005%) and tacalcitol ointment (20 μg/g)—restore pigmentation in vitiligo by inducing skin immunosuppression, which halts the local autoimmune process, and via direct activation of melanocytic precursors and melanogenic pathways.66 Some studies report more efficient repigmentation when vitamin D analogs are used in combination therapy, probably because of more complex stimulation of the repopulation process, targeting both melanocyte growth (with corticotherapy or UV) and differentiation (with a vitamin D analog). Vitamin D derivatives are indicated for use in localized disease; benefits include lack of skin atrophy and their easy application. However, their role in vitiligo treatment remains controversial; whereas some studies have reported substantial benefit, others found vitamin D analogs ineffective.45

Pseudocatalase

Pseudocatalase has been used to reconstitute deficient activity of catalase in vitiligo epidermis, degrading excessive H2O2 and allowing recovery of enzyme activities in vitiligo skin.67 Pseudocatalase monotherapy or combination with NB-UVB has shown apparent efficacy in repigmentation and prevention of disease progression in uncontrolled trials,68,69 while in other studies showed no substantial benefit.70–72 Therefore, its effect in vitiligo needs further validation.

Laser Therapy

UV B narrowband excimer laser (XeCl) and monochromatic excimer light (MEL) are currently used for treatment of localized vitiligo. These are similar to classical NB-UVB treatments, with the advantage of fewer side effects because only one lesion is treated at a time. These treatments produce optimal aesthetic results, with minor contrast between normal and affected skin.56 The XeCl has laser-coherent emission of monochromatic rays, whereas the MEL device can generate and selectively deliver 308-nm UVB light. No data for cancer risk and other long-term side effects are available; therefore, caution is currently advised.73

Surgical Treatment

Autologous skin grafts are an option for repigmentation only in patients with stable vitiligo that is refractory or only partially responsive to medical treatment, and in general limited in extent (less than 3% of body-surface area).43 The most frequent side effects are infection, postinflammatory hyperpigmentation, unaesthetic repigmentation, cobblestoning, and scarring.55 UV-light therapy generally hastens and improves repigmentation when combined with surgical methods.

Autologous skin graft approaches can be categorized into five principal groups.55 Of note, in the United States any procedure in which cells are manipulated (e.g., cultured) must be performed in a good manufacturing practices (GMP) facility.

Noncultured Epidermal Suspensions

This technique is performed by grafting noncultured suspensions containing both keratinocytes and melanocytes74,75 (eFigs. 74-9.1A and 74-9.1B); suspensions are obtained by 0.25% trypsin digestion of a thin piece of donor skin and are injected into blisters raised by liquid nitrogen freezing or seeded on recipient sites denuded by superficial dermabrasion. An advantage of this method is lack of scarring if recipient and donor sites are carefully manipulated.

Thin Dermal–Epidermal Grafts

Grafts are harvested at a depth of 0.1–0.3 mm, placed directly on recipient abraded areas next to each other, and are secured with surgical dressings under mild pressure for 1 week. Repigmentation occurs during the following weeks. Good results have been reported on dorsal hands and fingers.76,77

Minigrafting

Minigrafting represents the most commonly used current surgical method for vitiligo repigmentation (eFigs. 74-9.2A and 74-9.2B). Multiple perforations are made on recipient sites using 1.0–1.2-mm punches 3–4 mm apart from each other. Next, minigrafts are harvested from the donor site using a similar punch and are transferred to recipient sites with fine forceps or a hypodermic needle.78 Repigmentation occurs around each minigraft up to 2–5 mm by coalescence of spreading pigment. Good results are achieved in patients with refractory lip leukoderma, although the risk of cobblestoning seems to be high.76,79 An advantage of this method is its simplicity.

Epidermal Grafting

Grafts are harvested at negative pressure using different custom-made suction devices,55 the preferred donor sites being the inner aspect of the thigh and the flexor aspect of the forearm.80 Recipient sites are prepared by removing the epidermis using liquid nitrogen freezing or superficial dermabrasion81 or laser ablation.55 Epidermal grafts have been successfully used for lip vitiligo.82 The main advantage is the absence of scarring in donor and recipient sites.

In Vitro-Cultured Epidermis with Melanocytes and Melanocyte Suspensions55

Epidermis with Melanocytes

An epidermal suspension collected from a small donor skin sample is prepared by 0.25% trypsin digestion and seeded in culture flasks. After 3 weeks, epidermal sheets are harvested from the culture vessel and transplanted onto depigmented recipient sites previously denuded by liquid nitrogen freezing, superficial dermabrasion, lasers, or diatermo surgery. A hyaluronic artificial matrix for growing keratinocytes and melanocytes has also been used with success.83

Melanocyte Suspensions

In vitro-cultured melanocyte suspensions are obtained in a similar manner using specific and defined cultured media such as Ham's F12. During subculturing, pigment cells increase in number and may be transplanted onto denuded areas at a density of up to 100,000 melanocytes/cm2. The suspension spreads onto recipient areas and is covered for a week, providing a good cellular take.74,84 The large population of cells obtained from a small donor site represents a great advantage for treating extensive vitiligo areas in a single session.

Micropigmentation is useful for vitiligo lesions on mucous and mucocutaneous areas. It is accomplished by tattooing inert pigment granules into the dermis within collagen bundles and extracellularly at a depth of 1–2 mm, delivered by multiple electrically driven needles. Combinations of white, yellow, black, red, and brown pigments are used.55

Depigmentation

Some adult patients with extensive vitiligo may elect to undergo depigmentation of residual pigmented patches on facial and exposed areas. Depigmentation is achieved using 20% monobenzyl ether of hydroquinone (MBEH; monobenzone), which induces melanocyte loss via necrotic death without activating the caspase cascade or DNA fragmentation.85 MBEH is first applied as a patch test for 48 hours to detect hypersensitivity. Subsequently, twice-daily applications for at least a year are followed by irreversible depigmentation86 (Figs. 74-10A–D). Sunlight protection of depigmented skin is essential to prevent nonmelanoma skin cancers.55

We propose a treatment algorithm for vitiligo, considering the therapeutic approaches presented above (Fig. 74-11).

Camouflage, Sun Protection, and Psychological Support

Use of cosmetic camouflage, on the face and other exposed areas, and clothing to conceal affected areas can improve the quality of life for patients with vitiligo. Modern camouflage dyes and creams are waterproof, and the wide range of color and shades available can enable patients to choose the most suitable ones for their own skin color (Figs. 74-12A and 74-12B).

Tanning should be avoided since it enhances the contrast of vitiligo lesions with normally pigmented skin. Moreover, sunscreens are needed to prevent sunburn of depigmented unprotected skin. However, this is somewhat problematic, as moderate sun exposure (heliotherapy) in many cases can induce epidermal repopulation with melanocytes. As well, it has been suggested that skin friction due to repeated application of sunscreen might exacerbate the disease,43 although there is no evidence to support this hypothesis. Depigmented skin in vitiligo tends to show increased tolerance to UVB light over time (photoadaptation), with the extent of tolerance based in part on skin phototype, supposedly due to both pigmentary and nonpigmentary influences,87 although the specific mechanism remains unknown.

Psychological support may be beneficial to some patients. Listening to patients’ complaints and concerns and providing reassurance with advice about possible treatments and capacity for improvement is usually helpful for patients. Consider psychiatric evaluation for patients with marked low self-esteem and depression.

Nontraditional Treatments

A wide range of nontraditional treatments have been suggested for vitiligo, and some may be considered as alternative approaches for patients who either failed or are unsuitable for the above therapies. The most commonly used include vitamin and nutritional supplements, immunomodulators, human placental extracts, khellin, and topical and systemic phenylalanine, among many others. There is no convincing evidence that any of these nontraditional treatments is effective.

Prevention

Patients, patient support groups, and purveyors of alternative medicines have developed extensive and diverse hypotheses regarding vitiligo causation and approaches to its prevention. At present, there is no compelling evidence that any approach to vitiligo prevention is effective. Moreover, there is currently no useful approach to identify individuals at high risk for developing vitiligo.