Вы находитесь на странице: 1из 19

VITILIGO Vitiligo is a specific, common, often heritable, acquired disorder characterized by wellcircumscribed milky-white cutaneous macules devoid of identifiable

melanocytes. It carries a risk for ocular abnormalities, particularly iritis.1,5,6 Psychosocial implications of vitiligo Vitiligo, particularly in brown and black peoples and in Caucasian persons who can tan deeply [skin phototype (SPT) IV; see Chap. 88] may be a psychosocial disaster. Incidence Across the globe, vitiligo is a relatively common cause of leukoderma; although studies have demonstrated an incidence of 0.14 to 8.8 percent, the likely incidence is between 1 and 2 percent. All races are affected. Both sexes are affected equally; the female prevalence in some studies probably can be attributed to greater concern (and greater willingness to express concern) about a cosmetic defect. Vitiligo appears to be observed more commonly in sun-exposed areas and in darker skin types. About 85 percent of patients tan well, and only 15 percent sunburn in constitutively normal skin. SPT IV is the prevalent skin type among Caucasian vitiligo patients. Normal hair color may be black, brown, blond, or red, and the eyes may be blue, hazel, or brown. Black to dark-brown hair and brown iris color seem more common than expected. Vitiligo may develop at any age; onset has been reported from birth to 81 years of age. Congenital vitiligo is very rare, however. The peak age of onset in all series was between 10 and 30 years; in 50 percent of cases, the age of onset fell within the first two decades of life. Etiology Although vitiligo is generally recognized as a single entity, the etiology is complex. There appears to be a certain genetic predisposition and a number of potential precipitating causes. Heritability (Fig. 90-2)

FIGURE 90-2 Vitiligo (familial vitiligo). Vitiligo in mother and daughter. The daughter has typical generalized vitiligo, but the mother's condition has evolved to vitiligo universalis. Familial cases of vitiligo are common, strongly suggesting a genetic basis for this disorder. It is likely, however, that vitiligo is not transmitted in a simple Mendelian autosomal dominant or recessive pattern. The transmission is more complex, most likely polygenic with variable expression. Many studies on the relationship between the human leukocyte antigen (HLA)

system and vitiligo showed variable findings. An association between the catalase gene (CAT) and vitiligo has been suggested.7 A novel gene named VIT1, possibly associated with vitiligo, has been identified recently by differential display. The involvement of the GTP cyclohydrolase I gene (GTPCH), which encodes a key enzyme of the biopterin pathway, has been ruled out. The exact genetic defects in vitiligo remain to be elucidated, and the vitiligo susceptibility genes have not yet been identified. P.840

Precipitating factors Vitiligo patients often can attribute the onset of their disease to a specific life event, crisis, or illness. Many can relate it to loss of a job, death of a close family member, an accident, or a severe systemic disease. In some, the onset follows a physical injury such as a cut or abrasion; this development of vitiligo congruent with a site of injury is referred to as the Koebner phenomenon and is characteristic of at least a third of vitiligo patients. Many patients related onset to sun exposure; this may cause koebnerization in predisposed individuals. In darker-skinned individuals who have lost their previous summer tans, a single sun exposure may darken normally pigmented skin to reveal amelanotic macules not previously apparent. Gradual tanning of normal skin also reveals previously inapparent preexisting vitiligo macules that no longer tan. Clinical features TYPICAL MACULE OF VITILIGO The typical vitiligo macule has a chalk- or milk-white color, is round to oval in shape, has slightly brushed to fairly distinct, often scalloped margins, measures from several millimeters or many centimeters in diameter, and usually lacks other epidermal changes (Fig. 90-3). There are several variations on the typical vitiligo macule, however. Trichrome vitiligo (Fig. 90-4) refers to the presence of an intermediate color; this is a uniform tan coloration that is a narrow to broad interface between the normally pigmented skin and the typical vitiligo macule. An occasional vitiligo macule may be entirely off white to tan (tan being the third color). A trichrome lesion naturally evolves to a typical white vitiligo macule, albeit not at a predictable rate.

FIGURE 90-3 Vitiligo. Scalloping of the border of the remaining normal pigmentation suggests that the evolving hypopigmentation is invading the normally pigmented skin. Note that in this case (beard area) vitiligo is associated with alopecia areata.

FIGURE 90-4 Vitiligo. Trichrome vitiligo displays three colorswhite, light tan, and normal brown. The light tan area is metastable and will evolve to the amelanosis typical of vitiligo. Quadrichrome refers to the fourth color; this is a macular perifollicular or marginal hyperpigmentation seen in some cases of repigmenting vitiligo (especially in darker skin phototypes). The macules of hyperpigmentation vary from one to several millimeters in diameter. Pentachrome vitiligo (white, tan, brown hyperpigmented, blue-gray hyperpigmented, and normal) also may be observed. Blue vitiligo corresponds to vitiligo macules occurring in sites of postinflammatory hypermelanosis. Inflammatory vitiligo has an erythematous, raised border similar to that seen in tinea versicolor. Erythema of the entire macule of vitiligo occurs following sun exposure, but a vitiligo macule itself does not clinically resemble an inflammatory dermatosis. Confetti macules, which are typical in color but only 1 to 2 mm in diameter, may occur randomly or may be perifollicular. There may be one, several, or up to hundreds of macules that may be small to large in size, even in a single patient. As vitiligo naturally evolves over time, the macules enlarge, coalesce, and impart a scalloped appearance to the interface of the normal and vitiligo skin. When vitiligo becomes very extensive so that little normal pigment remains, the remaining islands of normal pigmentation have concave borders (as if the whole process were evolving) (see Fig 90-4), which is a diagnostic clue that distinguishes this process P.841 from hyperpigmented macules on normal, extremely fair skin. In actively repigmenting vitiligo, the margins lose their impressionistic character and become surrealistically sharp and again convex (representing foci of melanocytes migrating into vitiligo skin).

TYPES OF VITILIGO The following types represent the most characteristic patterns of vitiligo: focal, segmental, generalized, and universal. Focal vitiligo (see Fig. 90-3) is an isolated macule or a few scattered macules; by vague convention, the macules are limited in both size and number. Twenty percent of children with vitiligo have the focal pattern. Segmental vitiligo (Fig. 90-5) is characterized by unilateral macules in a dermatomal or quasi-dermatomal distribution. This should be considered a special type of vitiligo that has a stable course and is unlikely to be associated with thyroid disease or with other vitiligoassociated diseases. Segmental vitiligo tends to be earlier in onset and more stable than generalized vitiligo and is not familial. Involved patients are unlikely to develop remote or contralateral lesions. Koebnerization is not characteristic. Five percent of adults but more than 20 percent of children with vitiligo are found to have this pattern. The trigeminal area is the most common single site of involvement (>50 percent); the neck and trunk are involved in 23 and 17 percent, respectively. Up to 13 percent may have multiple sites of involvement. Nearly half are associated with poliosis (white hairs; see below). In various studies, from 5 to 28 percent of patients have been noted to have the segmental pattern.

FIGURE 90-5 Segmental vitiligo. Distribution is unilateral and quasidermatomal. Evolution is very unusual outside the generally involved dematome(s): rarely generalized vitiligo develops at a later date. Generalized vitiligo (Fig. 90-6) is the most common type of vitiligo and is characterized by few to many widespread macules. These macules are often symmetrically placed (Fig. 907A) and involve extensor surfaces; the most common extensor surfaces include interphalangeal joints, metacarpal/metatarsal interphalangeal joints, elbows, and knees. Other surfaces involved include volar wrists, malleoli, umbilicus, lumbosacral area, anterior tibia, and axillae. Vitiligo macules may be periorificial and involve the skin around the eyes, nose,

ears, mouth, and anus. Periungual involvement may occur alone or with certain mucosal surfaces (lips, distal penis, nipples); the latter is lip-tip vitiligo (Fig. 90-7B). Acrofacial vitiligo involves distal digits and periorificial facial areas. Universal vitiligo (vitiligo universalis) (Fig. 90-8) describes such widespread vitiligo that there are few remaining normal macules of pigmentation; this type has been associated with the multiple endocrinopathy syndrome.

FIGURE 90-6 Vitiligo. Generalized vitiligo in a patient with very extensive involvement. Note symmetry.

FIGURE 90-7 Vitiligo. Characteristic types and features. A. Symmetry. There is often nearly mirror-image symmetry as in this 14-year-old Indian girl. B. Lip-tip vitiligo. The coexistent involvement of the distal digits and the lips is a common subtype of vitiligo that also includes involvement of the areolae and the penis.

FIGURE 90-8 Vitiligo (vitiligo universalis). This patient, who developed total body vitiligo at the age of 9, also has Addison's disease, hypothyroidism, and cutaneous moniliasis. (Note onychomycosis of fingernails.) The general array of macules in generalized vitiligo is often remarkably symmetric, sometimes seemingly mirror image, but asymmetry is not unusual. An artifactual or atypically shaped macule may represent koebnerization and is a macule of vitiligo that corresponds exactly to the area of injury; a laceration will leave a macule of linear depigmentation, and a burn will leave an amelanotic lesion conforming to the exact area burnt. Shoulder-strap, waistband, and collar areasareas frequently rubbed by clothingseem particularly common sites. Involvement of bony prominences also may

represent koebnerization. Mucosal involvement is not infrequent; the genitalia, nipples, lips, and gingiva may be involved. Involvement of the palms and soles, once considered rare, can now be said to be rather common, although often unapparent without Wood's lamp examination, particularly in a fair-skinned individual. OTHER CUTANEOUS ABNORMALITIES Vitiligo may be associated with leukotrichia, prematurely gray hair, halo nevi, and alopecia areata. Depigmented hairs are found commonly in isolated vitiligo macules; leukotrichia (poliosis) has been reported in 9 to 45 percent of vitiligo patients. From one to all of the hairs in a macule may be white. Depigmented scalp hair occurs with or without an underlying vitiligo macule. Extensive white hair may be a marker for poor prognosis in repigmentation, but this may not apply for very small macules. Aside from macular leukotrichia, premature graying of hair (canities) occurs in up to 37 percent (see Chap. 91). Halo nevi appear relatively commonly. There may be one to many halo nevi. Confluence of these lesions in the stage of P.842 disappearance of the nevus leaves a typical vitiligo-like macule with scalloped borders. Alopecia areata has been reported in up to 16 percent of vitiligo patients (see Fig. 90-3). OCULAR ABNORMALITIES Vitiligo patients normally have no ophthalmologic complaints (except for the VogtKoyanagi-Harada syndrome, see below), but may have iris and retinal pigmentary abnormalities. Careful examination has revealed choroidal abnormalities in up to 30 percent and evidence of iritis in 5 percent. Visual acuity is normally unaffected. OTIC ABNORMALITIES Clinically significant hearing difficulties are not observed. However, deafness has been described in a cluster of patients on a small island where inbreeding and vitiligo are very common. In an audiometric study, no abnormalities implicating ear melanocytes could be found in a group of 93 vitiligo patients. SYSTEMIC DISEASE ASSOCIATIONS Many authors have reported an association of vitiligo and thyroid dysfunction, either hyperor hypothyroidism. Taking into account the high incidence of thyroid disease in the population, it is difficult to draw definitive conclusions about the association of vitiligo with thyroid dysfunction or the presence of thyroid antibodies in vitiligo patients, and this association is now questioned. Also, the validity of an association of vitiligo and diabetes mellitus is not obvious from the available data. Incidental association of vitiligo and Addison's disease, pernicious anemia, lymphomas, leukemias, and HIV infections has been reported. An increased incidence (13 percent) of vitiligo in patients with autoimmune polyendocrinopathy, candidiasisectodermal dystrophy (APECED), has been established. The gene mutated in this syndrome is called AIRE (autoimmune regulator). This association suggests that vitiligo, at least in a subset of patients, is an autoimmune disease. Diabetes mellitus, both juvenile- and adult-onset types, occurs in 1 to 7.1 percent of vitiligo patients, and conversely, vitiligo occurs in 4.8 percent of diabetic patients. The incidence of Addison's disease in vitiligo is said to be 2 percent but is likely much less common. Adrenal cortical and steroid cell antibodies do not appear increased in vitiligo patients. Pernicious anemia, although uncommon, occurs with increased frequency in vitiligo patients. The multiple endocrinopathy syndrome is found particularly among those with extensive vitiligo. P.843

Histology The current consensus is that no identifiable melanocytes are present in vitiligo macules. A recent report that melanocytes are not absent in lesional skin of long-duration vitiligo illustrates the dynamic nature of the melanocyte loss in vitiligo. The number of melanocytes in trichrome vitiligo, decreased in light-brown skin compared with perilesional normal skin and in vitiligo skin compared with light-brown skin, confirms the centrifugal progression of vitiligo lesions. In the dermis, few lymphocytes may be present in the upper dermis in involved macules and in inflammatory vitiligo with raised and erythematous borders. Melanin may be present in dermal macrophages in darker skin types.8 Vitiligo affects the entire epidermal melanin unit. Indeed, cytoplasmic vacuolization and/or the presence of extracellular granular material that may be derived from the cytoplasm of altered keratinocytes has been reported in the adjacent normal-appearing skin but also in the perilesional skin and rarely in the lesional hypomelanotic skin. The Langerhans' cell (LC) density in vitiligo macules has been variably reported as increased, normal, or decreased. The differences in the density of epidermal LCs in the various zones of trichrome vitiligo strongly suggest the involvement of LCs in the pathogenesis of this disorder. In addition, functional impairment of LCs has been documented in vitiligo skin. Repigmentation with PUVA is characterized by activation of inactive melanocytes from the middle and lower outer root sheath; this is followed by proliferation, division, migration, and maturation of melanocytes along with movement from the surface of the outer root sheath to the dermal-epidermal junction, where these appear as active melanocytes. Pathogenesis An undisputable fact in the pathogenesis of vitiligo is that there are no melanocytes present in the fully evolved white macules. Theories on the pathogenesis therefore center on mechanisms for the destruction of melanocytes. Traditionally, there have been three hypotheses to explain vitiligo9: the neural hypothesis, the self-destruct hypothesis, and the immune hypothesis. NEURAL HYPOTHESIS The neural hypothesis10 was based initially on anecdotal observations suggesting that stress and severe emotional trauma may initiate or precipitate vitiligo. The common embryologic origin of melanocytes, the nervous system, and the dermatomal distribution of segmental vitiligo are additional arguments put forward to support this view. Local physiologic abnormalities reflecting possible neuromediated aberrations have been reported in vitiligo patients. Direct contact between cutaneous free nerve endings and epidermal melanocytes has been demonstrated in vitiligo. The discovery of a wide range of neuropeptides in the skin and the demonstration that some of them are able to regulate melanocyte differentiation (melanogenesis, dendricity) have given more strength to the neural hypothesis. An increased immunoreactivity of neuropeptide Y (NPY) or an altered balance of nerve growth factor receptors and calcitonin generelated peptide have been observed in vitiligo skin. Alterations of the catecholamine pathway, increased catechol-o-ethyltransferase and monoamino oxidase activities, and increased expression of 2-adrenoreceptors have been described in vitiligo skin. These alterations are said to induce melanocyte dysfunction and melanocyte injury by promoting the production of melanocytotoxic compounds and by decreasing the natural detoxification-decreasing systems of melanocytes. At present, however, the role of the nervous system in vitiligo, if any, is poorly defined. Clinical evidence is misleading, since the so-called dermatomal or polydermatomal distribution of segmental vitiligo is, in fact, pseudodermatomal. THE SELF-DESTRUCT HYPOTHESIS According to the self-destruct hypothesis initially put forward by A. B. Lerner, melanocytes in vitiligo have lost an intrinsic protective mechanism that eliminates toxic intermediates or

metabolites in the melanogenesis pathway. This pathway is still not identified. The toxic potential of a large number of melanin precursors is well established. Chemicals such as monomethyl- and monobenzyl-ether of hydroquinone induce vitiligo-like hypomelanosis that is clinically and histologically indistinguishable from vitiligo. It has been suggested that the melatonin receptor and melatonin could play a key role in vitiligo. Indeed, melatonin is known to stimulate the melanogenic pathway without production of melanins, leading to an accumulation of toxic intermediate metabolites of the melanogenesis pathway. According to this hypothesis, these toxic products lead to melanocyte and keratinocyte injury with release of specific cellular proteins that initiate a secondary autoimmune reaction. However, this interesting theory is without any substantial experimental basis. The presence of melatonin receptors on melanocytes has not been demonstrated, and the role of melatonin in melanogenesis, if any, is unknown. Several reports provide evidence for increased oxidative stress in the entire epidermis of vitiligo patients.11 The presence of high epidermal H2O2 levels in vitiligo has been demonstrated, and low epidermal catalase levels in involved and uninvolved skin of vitiligo patients have been found. These findings suggest a major stress arising from increased epidermal H2O2 generation in vitiligo. Indeed, normal human melanocytes show an increased sensitivity to hydroperoxide in vitro. Protection of these cells against H2O2 cytotoxicity can be achieved in vitro by adding catalase to the culture medium. Several pathways could be involved in the overproduction of H2O2 in vitiligo. The first is an abnormality in tetrabiopterin metabolism leading to an overproduction of metabolites of this pathway, 6BH4 (6R)-L-erythro-5,6,7,8-tetrahydro- and 7BH4 (7R)-L-erythro-5,6,7,8tetrahydrobiopterin. This accumulation of 6- and 7-BH4 is detectable clinically by a characteristic yellow-green or bluish fluorescence on Wood's light examination. The defective recycling of 6-BH4 in vitiligo skin may lead to the formation of H2O2. Overproduction of H2O2 in vitiligo is claimed to result also from increased catecholamine biosynthesis in association with increased levels of monoamine oxidase A from inhibition of thioredoxin/thioredoxin reductase by calcium and increased nitric oxide synthase activities. THE AUTOIMMUNE HYPOTHESIS The putative association of vitiligo with autoimmune diseases has suggested an immunologic basis for vitiligo.12 This concept is now strongly supported by many recent studies. Involvement of humoral immunity was first demonstrated by the findings of circulating antibodies to melanocytes. The vitiligo antibodies are predominantly directed to various melanocyte antigens, including tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2. More recently, autoantibodies to a transcription factor called SOX10 have been found in vitiligo associated with polyglandular dysfunction (APECED) and in a small number of patients with isolated vitiligo. The level of these antibodies has been claimed to correlate with the disease activity and the extent of the cutaneous involvement. These vitiligo antibodies have the ability to kill human melanocytes in vitro. The best evidence that vitiligo antibodies play a role in melanocyte destruction is the observation of the disappearance of melanocytes from normal human skin engrafted onto nude mice injected with vitiligo patient sera. Evidence for a role of cellular immunity in vitiligo is even stronger. In marginal skin from progressing lesions of inflammatory and generalized vitiligo, an infiltrate of skinhoming (CLA+) cytotoxic T cells expressing granzyme/perforin is often found close to the remaining melanocytes. This infiltrate is composed of CD8+ T cells, CD4+ T cells, and subsets of macrophages, and this correlates with the increased numbers of CLA+ MART1reactive CD8+ T cells in the peripheral blood of patients with progressive vitiligo. In vitro, direct analysis of cutaneous T cells from margins of vitiligo macules demonstrates that they have a TH1 phenotype with a secretory repertoire including interferon- and tumor necrosis factor (TNF-). These specific cytotoxic T cells react against the melanocyte differentiation antigens Melan-A/MART-1, tyrosinase, and gp100 in vitiligo patients. These

CD4+ and particularly CD8+ T cells are associated with the destruction of melanocytes during active disease.13 It is still unknown whether P.844 these specific immune abnormalities are a cause or an effect of the disease, whether they damage melanocytes or aggravate melanocyte injury initiated by other causes, or are an irrelevant epiphenomenon. However, the presence of HLA-A2restricted melanocytespecific CLA+ CD8+ T lymphocytes is related to disease activity. Furthermore, melanocyteassociated vitiligo-like depigmentation is observed following successful immunotherapy of melanoma patients, with peptide-pulsed dendritic cells triggering tumor peptidespecific cytotoxic T cell responses. OTHER THEORIES Besides these three prevailing hypothesis, other possible pathomechanisms have been proposed: an intrinsic defect of the structure and function of the rough endoplasmic reticulum in vitiligo melanocytes,14 a deficiency in a melanocyte growth factor, a viral origin, a dysregulation of melanocyte apoptosis, and a primary disturbance of T lymphocytes resulting in the development of forbidden clones of autoreactive lymphocytes in the epidermis.9 ANIMAL MODELS Several animal models of vitiligo have been identified in horses, swine, and mice.15 The most interesting model is the Smyth chicken. These birds develop a delayed partial or total feather hypomelanosis. They also express many of the associated disorders presented by patients with vitiligo, including ocular depigmentation and uveitis, alopecia areatalike trait, autoimmune thyroiditis, and sometimes spontaneous repigmentation. The etiology of hypomelanosis in the Smyth chicken appears to include an inherent defect in the melanocytes followed by an autoimmune reaction involving antibody-producing B cells. Indeed, elimination of the humoral immune system in the Smyth chicken by neonatal bursectomy results in a significant decrease in the expression and severity of the feather amelanosis. From the available data, it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenic mechanisms. A convergence theory suggests that genetic factors, stress, accumulation of toxic compounds, infection, autoimmunity, mutations, altered cellular environment, and impaired melanocyte migration and proliferation can all contribute to the phenomenon.16 Present knowledge strongly suggests an immune pathogenesis, at least in a subgroup of vitiligo patients. However, the concept that the disorder we call vitiligo does not represent a single entity but constitutes a syndrome composed of a variety of different diseases is still valid.6 Diagnosis The diagnosis of generalized vitiligo in a patient with progressive, acquired chalk-white macules in typical sites is normally straightforward. Few such acquired conditions are so patterned and symmetric as vitiligo can be. Wood's lamp examination may be required to visualize macules in patients with lighter SPTs and to identify macules in sun-protected areas. The differential diagnosis of generalized vitiligo includes the following:

Chemical leukoderma: History of exposure to certain phenolic germicides, confetti macules Leprosy: Endemic area, anesthetic macules, off-white color Lupus erythematosus: Atypical distribution, inflammation, atrophy, positive immunofluorescence Melanoma-associated leukoderma: Different distribution, may disappear completely, may have melanocytes

Piebaldism: Congenital, white forelock, stable, large hyperpigmented macules, different distribution Pityriasis alba: Slight scaling, fuzzy margins, off-white color, ill-defined border Postinflammatory hypomelanosis: Off-white macules, ill-defined border, history of psoriasis, eczema in same areas Tinea versicolor: Fine scales with fluorescence under Wood's lamp, positive KOH Tuberous sclerosis: Congenital, white macules, occasional segmental and confetti macules, stable Waardenburg's syndrome: Widely spaced inner canthi, heterochromia, broadened nasal root, deafness

Segmental vitiligo is confined to one unilateral quasi-dermatomal distribution, and the following should be excluded:

Nevus depigmentosus: Unusually congenital, stable to progressive, hypomelanotic as opposed to amelanotic Tuberous sclerosis: Usually associated with typical white ash-leaf macules or confetti macules elsewhere; hypomelanotic, not amelanotic Idiopathic guttate hypomelanosis: Porcelain-white macule, discrete margins, may be slightly depressed

A solitary white macule or several white to off-white macules often present a challenge because they may be the presenting stage in the evolution of any of the processes listed above. In some instances, a biopsy may be helpful, but standard histologic studies cannot distinguish a vitiligo macule from one of chemical leukoderma, piebaldism, or WS. Biopsy is useful to establish diagnoses such as lupus erythematosus, leprosy, and tinea versicolor. The presence of melanin or melanocytes in a biopsy cannot be assumed to exclude a diagnosis of vitiligo because trichrome vitiligo, marginal (vitiligo) skin, and repigmenting macules of vitiligo also demonstrate melanocytes. Once the diagnosis has been established, testing for vitiligo-associated diseases is indicated. Natural course The natural course of vitiligo is unpredictable. Focal vitiligo, although stable for a time, may be a precursor of generalized vitiligo. The natural course of common vitiligo is often one of abrupt onset, followed by progression for a time; then a period of stability follows and may last for some time, even decades. This may be followed later by a period of more rapid evolution. Total spontaneous regression is rare, and evolution to vitiligo universalis is unusual, although not rare. The most common course is one of gradual evolution of existing macules and periodic development of new ones. Segmental vitiligo, on the other hand, is usually very stable. The period of evolution is often less than a year, after which there is little extension or regression; significant spontaneous repigmentation is unusual. Treatment While there are several options in the management of vitiligo, most patients require reassurance and an understanding of their affliction. In an increasingly sophisticated world, many patients present with a certain level of knowledge of their options. All patients should be encouraged to use sunscreens to protect the vitiliginous areas, reassured that the use of cosmetic coverup is perfectly acceptable, and educated about the benefits and risks of attempts at repigmentation and depigmentation.17,18 Additional information is available through support groups, printed brochures, and the Internet.

Professional counseling should be offered to those particularly distressed over their appearance. Patients suffering untoward life disruption in personal or professional relationships particularly should be encouraged to seek help. Sunscreens offer both protection from sunburn reaction with possible resulting koebnerization and attenuation of facultative tanning of normally pigmented skin; were the latter successful, the contrast between vitiligo macules and normal skin remains minimal, as is the case in the winter months or on habitually unexposed areas of skin. Opaque sunblocks with a sun protection factor (SPF) of over 30, containing ZnO and/or TiO2, are most suited for this purpose (see Chap. 247). Daily use of opaque sunscreens alone may be adequate management for those who are melanodeficient (tan weakly). Cosmetics, including conventional makeups, dyes, and self-tanning preparations, provide quick and practical solutions that are perfectly adequate for many patients. Certain specialized, thicker cosmetics are readily available and can be custom mixed to match most skin colors. Because cosmetics do rub off, they may be of limited value P.845 for the lower neck and wrists (rub off on clothing) and hands (because of handshaking). These areas may be better covered with dyes or self-tanning agents or one of the many cosmetic stains, respectively. A formulation containing 5% dihydroxyacetone in an oil-inwater emulsion base is practical and well accepted in vitiligo patients. However, the stains are usually modestly satisfactory at best and do tend to wash off. Patients need to be reassured that none of these preparations will cause their vitiligo to progress, nor will they preclude success of other options. Repigmentation involves any attempt to reverse the depigmentation and to reestablish normal pigmentation in established macules of vitiligo. Systematic review of the literature reveals that only a few randomized clinical trials have been performed on vitiligo therapies. All current attempts should be viewed as treatments or quasi-remissive techniques and not as a cure. Current available options include topical glucocorticoids for limited vitiligo, topical PUVA for focal and segmental types, PUVA-grafting (see below) for refractory segmental vitiligo or stable vitiligo, narrow-band ultraviolet B (UVB) therapy and oral PUVA for segmental or generalized vitiligo. All forms of treatment require a certain commitment from patients and should be undertaken with the full understanding of the advantages and limitations of each approach (discussed below). A meta-analysis of the literature concludes that class 3 glucocorticoids and UVB therapy are the most effective and safest therapies for localized and generalized vitiligo, respectively.18 Topical glucocorticoids have proven effective for isolated macules in some cases, but overall results tend to be disappointing. Hydrocortisone may be used for isolated macules in sensitive areas such as the face and axillae and for children. More potent topical steroids generally are more successful. However, with the most potent topical steroids, the approach should be daily application for 3 weeks, skip a week, and repeat to avoid local glucocorticoid side effects. If there has been no response after 2 months, treatment should be abandoned. If treatment is to be continued, monitoring every 2 months for signs of atrophy is prudent; irreversible striae may develop on the legs after as little as 4 months of continuous treatment. Topical steroids may be used in conjunction with other modalities. PUVA is indicated in patients for whom no other option is satisfactory and in patients who understand its limitations (see Chap. 266 and Fig. 90-9). Concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo whereas calcipotriol monotherapy is uneffective.

FIGURE 90-9 PUVA treatment of vitiligo. A. Typical symmetric periorificial vitiligo with characteristic involvement of the skin overlying the interphalangeal joints. B. After treatment there is marked hyperpigmentation, often seen in darker skin types. C. After discontinuation of treatment, the hyperpigmentation has faded, but the facial macules have remained filled in. A remarkable amount of repigmentation was also noted on the hands. Narrow-band UVB is presently considered a treatment of choice for vitiligo.19 Narrow-band fluorescent tubes (e.g., Philips TL-01/100 W) with an emission spectrum of 311 nm are used for this therapy. For a detailed discussion of PUVA and narrow-band UVB for vitiligo, see Chap. 266 and Chap. 265, respectively. Focused microphototherapy delivers UVB light with a spectrum of 280 to 315 nm only on the hypomelanotic skin. About 25percent of patients have excellent results. Unfortunately, this therapy requires expensive equipment and trained personal and therefore will not be available for many patients. Numerous surgical techniques have been reported to be successful in repigmentation,20 but it should be noted that no controlled studies are available. Regardless of the surgical technique, segmental vitiligo is the best candidate for surgical intervention. Vitiligo, which always carries the risk of koebnerization, may be considered suitable for surgical interaction in those cases in which the vitiligo is limited in area and has been stable for some time (2 years). In most cases, pretreatment with PUVA will establish those islands of inapparent melanocytes capable of repigmenting and define sites that have no ability to repigment. The P.846 minigrafting test described by Falabella and colleagues is particularly useful in predicting success (or failure) in minigrafting of stable vitiligo; in all patients, the results demonstrate to the patient the expected cosmetic appearance of the graft and donor sites. The patient and the physician together then may decide if proceeding with extensive grafting will likely be satisfactory. Various surgical techniques have been described. Transplantation of cultured autologous melanocytes to depigmented macules has led to excellent results, but the method is tedious. Up to 6 to 8 months are required for an excellent color blend. The grafts are generally stable over the 1 to 2 years of follow-up. Falabella reported that even the dorsal hands can be grafted successfully.20 Cryostorage of excess cultured melanocytes is a source of melanocytes for future procedures.

Minigrafting with 1- to 2-mm punch grafts or split-skin grafts may be most practical for isolated small macules. Placement of four 1.5-mm grafts per square centimeter is a practical technique; pigment spread beyond the graft site should be visible within a month. PUVA may be required to complete the repigmentation (Fig. 90-10). Hyperpigmentation and pebbling may be observed but generally will reverse over time. Patients with stable vitiligo without koebnerization seem to be the best surgical candidates; reversal of leukotrichia also has been observed. Permanent dermal micropigmentation using a nonallergic iron oxide pigment can be used to cover recalcitrant areas of vitiligo.21

FIGURE 90-10 Vitiligo. Treatment with grafting. A. Vitiligo macule unresponsive to PUVA. B. Same macule after grafts have been placed; pigmentation begins to spread outward from the graft site. C. Repigmentation of the macule. PUVA may sometimes be required after

grafting to complete the repigmentation. (Courtesy of WL Morison, MD, and J. Skouge, MD.) OTHER THERAPIES Multivitamin therapy (folic acid/vitamin B12/ Vitamin C) has been reported to show repigmentation, particularly in children. Melagenina (placental therapy) generally has proven disappointing outside of Cuba, where it was first described. Likewise, phenylalanine/UVA (PAUVA) generally has been inconsistent. The combination of calcium, pseudocatalase, and UVB has been reported to result in repigmentation even of such refractory areas as the dorsal hand; this improved response plus the relevance of this therapy to new understanding of the disease makes this approach particularly exciting. However, this open study has not yet been confirmed. Oral administration of compounds such as ubiquinone, tocopherol, selenium, and methionine in vitiligo patients is common practice among dermatologists. No controlled study demonstrating the efficacy of antioxidant therapy is yet available. Depigmentation is another option (Table 90-2) for those with extensive vitiligo and/or in those who have failed PUVA, for whom PUVA is not an option, or who have rejected it (Fig. 90-11). Bleaching, which implies destruction of residual melanocytes with monobenzylether of hydroquinone (MBEH) 20% cream is a permanent, irreversible process. Application of MBEH may be associated with satellite depigmentation; therefore, MBEH cannot be used selectively to bleach just limited areas of normal pigmentation; the risk of distant and remote macules of depigmentation is very real. The patient may elect to treat all residual pigmentation or just selected cosmetically bothersome areas. Successful bleaching with MBEH requires twice-daily application for 2 to 3 months before improvement is observed and 9 to 12 months before complete depigmentation is achieved. Up to 50 percent of patients may complain of erythema, dryness, burning, and pruritus, particularly on the face; these symptoms may be diminished by reducing the frequency of use or by mixing the MBEH with an emollient. Contact dermatitis restricted to normally melanized skin occurs in nearly 15 percent of users.22 Between 90 and 95 percent of patients will be fully bleached in a year. Maintenance applications are not required. However, although this depigmentation is P.847 normally considered to be irreversible, an occasional patient will observe focal repigmentation following sun exposure, which requires reapplication of MBEH for a month or more. Assiduous avoidance of midday sun and routine use of high-SPF opaque sunblocks usually minimize this risk. There have been no long-term untoward effects from the use of MBEH.

FIGURE 90-11 Vitiligo. Treatment of normal skin by depigmentation with 20% monobenzylether of hydroquinone. A. Dark-skinned patient with extensive vitiligo before therapy. B. Permanent depigmentation after a year of application of 20% monobenzylether of hydroquinone cream. The patient has remained uniformly depigmented for over 15 years.

TABLE 90-2 Monobenzylether of Hydroquinone Therapy of Vitiligo Some patients who have bleached may wish to attenuate the chalk-white appearance of their skin; this may be achieved by daily ingestion of 30 to 60 mg of beta-carotene; the intensity of the color may be adjusted by increasing or decreasing the dose. TREATMENT OF VITILIGO IN CHILDREN There is a particular challenge in the treatment of vitiligo in children, for the complex parentchild relationship may bear heavily on what is asked of the dermatologist. The compelling principle is to segregate the needs of the child from those of the parent. Often it is the parent, not the child, who is concerned; in this case it is the parental worries that must be addressed. In some regions, support groups are available and can be quite helpful. Sunscreens and cover-up are the initial steps. The next is topical steroids, which may take weeks to be effective. In certain cases of limited vitiligo, topical psoralens may be considered. Narrow-band UVB therapy is the treatment of choice for children (over 6 years). Oral psoralens may be considered after maturity of the ocular lens can be reasonably assured (about age 10). The specifics of each approach are the same as for adults.

Вам также может понравиться