VITILIGO

Vitiligo Vitiligo is a major medical problem for brown and black persons that can result in severe difficulties in social adjustment. Vitiligo is characterized clinically by development of totally white macules, microscopically by complete absence of melanocytes, and medically by a not uncommon association with certain medical diseases, particularly thyroid disease. Epidemiology Sex Equal in both sexes. The predominance in women suggested by the literature likely reflects the greater concern of women about cosmetic appearance. Age of Onset May begin at any age, but in 50% of cases it begins between the ages of 10 and 30 years. A few cases have been reported to be present at birth; onset in old age also occurs but is unusual. Incidence Common. Affects up to 1% of the population. Race All races. The apparently increased prevalence reported in some countries and among darker-skinned persons results from a dramatic contrast between white vitiligo macules and dark skin and from marked social stigma in countries such as India, where even today the opportunities for advancement or marriage among affected individuals are limited. Inheritance Vitiligo has a genetic background; >30% of affected individuals have reported vitiligo in a parent, sibling, or child. Vitiligo in identical twins has been reported. Transmission is most likely polygenic with variable expression. The risk of vitiligo for children of affected individuals is unknown but may be <10%. Individuals from families with an increased prevalence of thyroid disease, diabetes mellitus, and vitiligo appear to be at increased risk for development of vitiligo. Pathogenesis Three principal theories have been presented about the mechanism of destruction of melanocytes in vitiligo: 1. The autoimmune theory holds that selected melanocytes are destroyed by certain lymphocytes that have somehow been activated. 2. The neurogenic hypothesis is based on an interaction of the melanocytes and nerve cells. 3. The self-destruct hypothesis suggests that melanocytes are destroyed by toxic substances formed as part of normal melanin biosynthesis. While the immediate mechanism for the evolving white macules involves progressive destruction of selected melanocytes by cytotoxic T cells, other genetically determined cytobiologic changes and cytokines must be involved. Because of differences in the extent and course of segmental and generalized vitiligo, the pathogenesis of these two types must be somewhat different. History Many patients attribute the onset of their vitiligo to physical trauma (where vitiligo appears at the site of trauma—Koebner phenomenon), illness, or emotional stress. Onset after the death of a relative or after severe physical injury is often mentioned. A sunburn reaction may precipitate vitiligo. Physical Examination Skin Lesions Macules, 5 mm to 5 cm or more in diameter . "chalk" or pale white, sharply marginated. Newly developed macules may be "off-white" in color; this represents a transitional phase. The disease progresses by gradual enlargement of the old macules or by development of new ones. A variant is trichrome vitiligo (three colors: white, light brown, dark brown) but this represents different stages in the evolution of vitiligo. Pigmentation around a hair follicle in a white macule represents residual pigmentation or returnof pigmentation . Confetti-sized hypomelanotic macules may also be observed. Inflammatory vitiligo has an elevated erythematous margin and may be pruritic. Margins are convex (as if the pathologic process of depigmentation were flowing into normally pigmented skin). Distribution Depigmentation occurs in three general patterns. The focal type is characterized by one or several macules in a single site; this may be an early evolutionary stage of one of the other types in some cases. The segmental type is characterized by one or several macules in one band on one side of the body; this type is associated rarely with distant vitiligo macules or with further evolution of the disease to generalized vitiligo. The most common type is generalized vitiligo, characterized by widespread distribution of depigmented macules, often in a remarkable symmetry . Typical macules occur around the eyes  and mouth and on digits, elbows, and knees, as well as on the low back and in genital areas . The "lip-tip" pattern involves the skin around the mouth as well as on distal fingers and toes; lips, nipples, genitalia (tip of the penis), and anus may be involved. Confluence of vitiligo results in large white areas, and extensive generalized vitiligo may leave only a few normally pigmented areas of skin—vitiligo universalis Universal vitiligo Vitiliginous macules have coalesced to involve all skin sites with complete depigmentation of skin and hair in a female. The patient is wearing a black wig and has darkened the brows with eyebrow pencil and eyelid margins with eye liner Segmental Vitiligo This is a special subset that usually develops in one unilateral region; usually does not extend beyond that initial one-sided region (though not always); and, once present, is very stable. Associated Cutaneous Findings White hair and prematurely gray hair. Circumscribed areas of white hair, analogous to vitiligo macules, are called poliosis. Alopecia areata and halo nevi. In older patients, photoaging as well as solar keratoses may occur in vitiligo macules in those with history of long exposures to sunlight. Squamous cell carcinoma, limited to the white macules, has rarely been reported. General Examination Not uncommonly associated with thyroid disease (up to 30% of all vitiligo cases: Hashimoto's thyroiditis, Graves' disease); also diabetes mellitus—probably <5%; pernicious anemia (uncommon, but increased risk); Addison's disease (uncommon); and multiple endocrinopathy syndrome (rare). Ophthalmologic examination may reveal evidence of healed chorioretinitis or iritis (probably <10% of all cases). Vision is unaffected. Hearing is normal. The Vogt-Koyanagi-Harada syndrome is vitiligo + poliosis + uveitis + dysacusia + alopecia. Laboratory Examinations Wood's Lamp Examination Wood's lamp examination is required to evaluate macules, particularly in lighter skin types, and to identify macules, in sun-protected areas in all but the darkest skin types. Dermatopathology In certain difficult cases, a skin biopsy may be required. Established vitiligo macules show normal skin except for an absence of melanocytes. Use special stains to identify melanocytes. There may be a mild lymphocytic response. These changes are not diagnostic for vitiligo, however, only consistent with it. Electron Microscopy Absence of melanocytes and of melanosomes in keratinocytes; also changes in keratinocytes: spongiosis, exocytosis, basilar vacuopathy, and necrosis. Lymphocytes have been seen in the epidermis. Laboratory Studies T4, TSH (radioimmunoassay), fasting blood glucose, complete blood count with indices (pernicious anemia), ACTH stimulation test for Addison's disease, if suspected. Diagnosis Normally, diagnosis of vitiligo can be made readily on clinical examination of a patient with progressive, acquired, chalk-white, bilateral (usually symmetric), sharply defined macules in typical sites (periorbital, perioral, neck, penis, perineum, axillae, and points of pressure such as the elbow, malleoli, knees, lumbosacral area). Note: Vitiligo is a sharply marginated, macular depigmentation of otherwise completely normal skin. Differential Diagnosis Pityriasis alba (slight scaling, fuzzy margins, off-white color). Pityriasis versicolor alba (fine scales with greenish-yellow fluorescence under Wood's lamp, positive KOH. Chemical leukoderma (history of exposure to certain phenolic germicides, confetti macules). This is a difficult differential diagnosis, as melanocytes are absent as in vitiligo. Leprosy (endemic areas, off-white color, usually ill-defined anesthetic macules). Nevus depigmentosus (stable, congenital, off-white macules, unilateral). Hypomelanosis of Ito (bilateral, Blaschko's lines, marble cake pattern; 60 to 75% have systemic involvement–CNS, eyes, musculoskeletal system). Nevus anemicus (does not enhance with Wood's lamp; does not show erythema after rubbing). Tuberous sclerosis [stable, congenital off-white macules (polygonal, ash-leaf shape, occasional segmental macules, and confetti macules)]. Piebaldism (congenital, white forelock, stable, dorsal pigmented stripe on back, distinctive pattern with large hyperpigmented macules in the center of the hypomelanotic areas). Leukoderma associated with melanoma (may not be true vitiligo inasmuch as melanocytes, although reduced, are usually present). Postinflammatory leukoderma [off-white macules (usually a history of psoriasis or eczema in the same macular area), not so sharply defined]. Mycosis fungoides (may be confusing as only depigmentation may be present and biopsy is necessary). Vogt-Koyanagi-Harada syndrome (vision problems, photophobia, bilateral dysacousia). Waardenburg's syndrome (commonest cause of congenital deafness, white macules and white forelock, iris heterochromia). Course and Prognosis Vitiligo is a chronic disease. The course is highly variable, but rapid onset followed by a period of stability or slow progression is most characteristic. Up to 30% of patients may report some spontaneous repigmentation in a few areas—particularly areas that are exposed to the sun. Rarely is this sufficient to satisfy the cosmetic burden that the patient feels. Rapidly progressive or "galloping" vitiligo may quickly lead to extensive depigmentation with a total loss of pigment in skin and hair, but not eyes. The treatment of vitiligo-associated disease (i.e., thyroid disease) has no impact on the course of vitiligo. Management The approaches to the management of vitiligo are as follows: Sunscreens The dual objectives of sunscreens are protection of involved skin from acute sunburn reaction and limitation of tanning of normally pigmented skin. Sunscreens with a sun protection factor >30 are reasonable choices to prevent sunburn for most patients. However, since their ability to limit the tanning reaction is inversely proportional to SPT, opaque sunscreens should be more effective in limiting the tanning reaction in fairer-skinned individuals. While all SPTs have a need for sun protection, sunscreens alone are often perfectly adequate management for those vitiligo patients with SPTs I, II, and sometimes III. Cosmetic Coverup The objective of coverup with dyes or makeup is to hide the white macules so that the vitiligo is not apparent. Over-the-counter preparations come in many color shades, are easy to apply, and do not rub off but gradually wash or wear off. So-called self-tanning agents, which contain dihydroxyacetone, are available in a number of formulations. Repigmentation The objective of repigmentation  is the permanent return of normal melanin pigmentation. This may be achieved for local macules with topical glucocorticoids or topical psoralens and UVA (long-wave ultraviolet light) and for widespread macules with oral psoralens and UVA