Vitiligo Background: Vitiligo is a specific type of leukoderma characterized by depigmentation of the epidermis. Occasionally, the loss of melanin (ie, hypopigmentation) is partial. It is an acquired progressive disorder in which some or all of the melanocytes in the interfollicular epidermis, and occasionally those in the hair follicles, are selectively destroyed. Pathophysiology: Mechanisms by which the melanocytes are lost may be multiple but are not yet identified unequivocally. Some observations seem to support autosomal dominant inheritance with variable expression and incomplete penetrance. The disease itself is not inherited, but the disposition to have vitiligo is inherited. Human leukocyte antigens (HLAs) may be associated but not in a consistent manner: 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: Internationally: Vitiligo is relatively frequent, with a rate of 1-2%. About 30% of cases occur with a familial clustering of cases. Sex: No sex-related difference in prevalence is reported. The age of onset is unlikely to vary between the sexes. Age: Vitiligo may appear at any time from birth to senescence, though 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 around 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 women. History: In early vitiligo, white areas are not distinct and may be pruritic. Vitiligo primarily progresses without any symptoms. In late vitiligo, the tendency of the disease to spread can be stopped. Physical: Vitiligo appears as sharply circumscribed, cosmetically disturbing, white spots that stand out. The appearance is particularly noticeable when the unaffected skin is tanned. At first, only a few, small, and sharply circumscribed foci are present. The borders of these foci are often hyperpigmented. Lesions increase in number and become confluent, taking on bizarre shapes. Vitiligo lesions may be localized or generalized, with the latter being more common than the former. Localized vitiligo is restricted to 1 general area with a segmental or quasidermatomal distribution. Generalized vitiligo implies more than 1 general area of involvement. In this situation, the macules are usually found on both sides of the trunk, either symmetrically or asymmetrically arrayed. 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 mucus membrane is frequently observed in the setting of generalized vitiligo. Vitiligo often occurs around body orifices such as the lips, genitals, gingiva, areolas, and nipples. Depigmentation of body hair in vitiliginous macules may be present. 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 eyebrow, pubic, and axillary hair, respectively. Leukotrichia may indicate a poor prognosis in regard to repigmentation. Clinical variants Trichrome vitiligo has an intermediate zone of hypochromia located between the achromic center and the peripheral unaffected skin. This results in three shades of color-brown, tan, and white-in the same patient (see Image 1). Marginal inflammatory vitiligo results in a red, raised border, which are present from the onset of vitiligo (in rare cases) or which may appear several months or year after the initial onset. A mild pruritus may be present (see Image 2). Blue vitiligo results in blue coloration of vitiligo macules. This type has been observed in a patient with postinflammatory hyperpigmentation who then developed vitiligo. Clinical classification of vitiligo: The classification system is important because of the special significance assigned by some authorities to each type of vitiligo. The widely used classification of vitiligo as localized, generalized, and universal types is based on the distribution, as follows: Localized Focal - One or more macules in 1 area but not clearly in a segmental or zosteriform distribution Segmental - One or more macules in a quasidermatomal pattern Mucosal - Mucus membrane alone Generalized Acrofacial - Distal extremities and face Vulgaris - Scattered macules Mixed - Acrofacial and vulgaris involvement, or segmental and acrofacial and/or vulgaris involvement Universal - Complete or nearly complete depigmentation When progression, prognosis, and treatment are considered, vitiligo can be classified into 2 major clinical types: segmental and nonsegmental. Segmental vitiligo 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 Image 3). The nonsegmental type includes all types of vitiligo except segmental vitiligo (see Image 4). Causes: Four pathogenic theories have been discussed, as follows: Immune hypothesis: Aberration of immune surveillance results in melanocyte dysfunction or destruction. Neural hypothesis: A neurochemical mediator destroys melanocytes or inhibits melanin production. Self-destruction hypothesis: An intermediate or metabolic product of melanin synthesis causes melanocyte destruction. Genetic hypothesis: 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. 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. Systemic phototherapy induces cosmetically satisfactory repigmentation in up to 70% of early or localized cases. PUVA treatment (8-methoxypsoralen, 5-methoxypsoralen, trimethylpsoralen plus UVA) was often the most practical choice for treatment, especially in widespread vitiligo in patients with skin types IV-VI. However, 2 or 3 treatments per week for many months are required before repigmentation from perifollicular openings merges to produce confluent repigmentation. The best results can be obtained on the face and on the proximal parts of extremities. Vitiligo on the back of hands and feet is very resistant to therapy. Narrowband UV-B phototherapy was recently developed and widely being used with good clinical results. Narrowband fluorescent tubes (Philips TL-01/100W) with an emission spectrum of 310-315 nm and a maximum wavelength of 311nm are used. Treatment frequency is twice weekly and never on consecutive days. This treatment can be safely used in children, as well as pregnant and lactating women. UV-B narrowband microphototherapy is targeting the specific small lesions. Selective narrowband UV-B (311 nm) is used with a fiber optic system to direct radiation to specific areas of skin. Another recent innovation is therapy with an Excimer laser that produces monochromatic rays at 308-nm to treat limited, stable patches of vitiligo. These new treatments are efficacious, safe, and well-tolerated treatment for vitiligo when limited to less than 30% of the body surface. However, they are expensive. Systemic steroids (prednisone) have been used, though their prolonged use and toxicity are undesirable. Steroids have been given with anecdotal success in pulse doses or low doses to minimize adverse effects. Benefits and toxicity of this therapy must be weighed carefully. More research is necessary to establish 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. 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 inflammation is subclinical. Topical tacrolimus ointment (0.03% or 0.1%) is an effective alternative therapy for vitiligo, particularly when the disease involves the head and neck. Combination treatment with topical tacrolimus 0.1% plus the 308-nm Excimer laser is superior to monotherapy with the 308-nm Excimer laser monotherapy for UV-resistant vitiliginous lesions. The combination of topical calcipotriene and narrowband UV-B or PUVA results in improvement appreciably better than achieve with monotherapy. If vitiligo is widespread and attempts at repigmentation do not produce satisfactory results, depigmentation may be attempted in selected patients. 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. 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. It is applied 30 minutes prior to UV-A radiation (usually 0.1-0.3 J/cm2 UV-A). 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. 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. Tanning of surrounding normal skin exaggerates the appearance of vitiligo, and this is prevented by sun protection. Sunscreens with a sun protection factor (SPF) of 15 or higher are best. Surgical Care: Patients who have small areas of vitiligo with stable activity are candidates for surgical transplants. Punch grafts Punch biopsy specimens from a pigmented donor site are transplanted into depigmented sites. Repigmentation and spread of color begin about 4-6 weeks after grafting. The major problem is a residual, pebbled, pigmentary pattern. Minigrafts 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. Suction blister 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. Autologous cultures and autologous melanocytes grafts: These 2 techniques are expensive and currently impractical. Micropigmentation 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, though the color match is often poor. The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Drug Category: 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. Drug Name Triamcinolone (Aristocort) -- 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%). Adult Dose 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 Dose Apply as in adults Contraindications Documented hypersensitivity; fungal, viral, and bacterial skin infections Interactions Coadministration with barbiturates, phenytoin, and rifampin decreases effects of triamcinolone Pregnancy C - Safety for use during pregnancy has not been established. 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 Drug Name Hydrocortisone (Westcort) -- 0.2%. Adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. Has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity. Adult Dose Apply sparingly to affected areas tid Pediatric Dose Apply as in adults Contraindications Documented hypersensitivity; viral, fungal, and bacterial skin infections Interactions None reported Pregnancy C - Safety for use during pregnancy has not been established. Precautions Prolonged use, application over large surface areas, application of potent steroids and occlusive dressings may increase systemic absorption and cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria Drug Name Prednisone (Deltasone) -- Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. Use for 8 wk with taper. Adult Dose 20 mg PO qd for 4 wk; then 10 mg PO qd for 4 wk; taper over 2 wk, as symptoms resolve Pediatric Dose 4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk, as symptoms resolve Contraindications Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease Interactions Coadministration with estrogens may decrease prednisone clearance; when used with digoxin, digitalis toxicity due to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use Drug Category: Psoralens -- These agents are used with UV-A exposure for the treatment of localized or generalized vitiligo. Drug Name Methoxsalen (8-MOP, Oxsoralen) -- Inhibits mitosis by covalently binding to pyrimidine bases in DNA when photoactivated by UV-A. Effective in treating hyperkeratosis. Adult Dose 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 0.1% ointment: Apply 30 min before controlled UV-A exposure once or twice weekly Pediatric Dose <12 years: Not recommended >12 years: Administer as in adults 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 Interactions Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamide Pregnancy C - Safety for use during pregnancy has not been established. 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 Drug Name Trioxsalen (Trisoralen) -- For treatment of hyperkeratosis. In UV-A radiation, inhibits mitosis by covalently binding to pyrimidine bases in DNA. Adult Dose 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 Dose <12 years: Not recommended >12 years: Administer as in adults Contraindications Documented hypersensitivity; a history of melanoma, acute lupus erythematosus, and porphyria; inability to comply with instructions regarding UV-A exposure and eye protection Interactions None reported Pregnancy C - Safety for use during pregnancy has not been established. 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 Drug Name Tacrolimus (Protopic) ointment 0.03% or 0.1% Adult Dose Apply to the affected area twice daily, continue for 1 week after signs and symptoms resolve, avoid occlusive dressings Pediatric Dose Protopic 0.03% only: Apply as in adults 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 of the ingredients; patients receiving UV therapy, such as PUVA; Netherton syndrome (high possibility of increased systemic absorption) Interactions Formal studies not conducted. Because of minimal absorption, interactions with systemic drugs are unlikely but not ruled out. Caution with concomitant administration of known CYP3A4 inhibitors (eg, erythromycin, itraconazole, ketoconazole, calcium channel blockers, cimetidine) in patients with widespread and/or erythrodermic disease. Pregnancy C - Safety for use during pregnancy has not been established. Precautions Clinical infection should be resolved first; in patients with atopic dermatitis exposed to superficial skin infection (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 transplant 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 with improvement with atopic dermatitis resolves Drug Name Calcipotriene Adult Dose Apply to affected areas bid (q am and at qh before retiring and after washing); apply thin film, avoiding eyes and lips; do not cover with occlusive dressing. Pediatric Dose Not recommended Contraindications Systemic treatment of calcium deficiency; kidney or liver dysfunction; hypercalcemia or calcium metabolism problems. Interactions Substances that stimulate absorption should not be administered concomitantly because of potential effects on calcium metabolism. Pregnancy C - Safety for use during pregnancy has not been established. 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/day. Medical/Legal 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 onset of hypothyroidism, diabetes, or other autoimmune disease. 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. Picture 1. Trichrome vitiligo. Picture 2. Marginal inflammatory vitiligo. Picture 3. Segmental vitiligo. Picture 4. Nonsegmental vitiligo. Source: http://www.emedicine.com/DERM/topic453.htm