Vitiligo is a major medical problem for brown and black persons that can result in severe difficulties in social adjustment. Therefore, it is important for physicians to be aware of the various options for control of this disease. There are some successful therapeutic approaches, and these should be explained to the patient. The patient with vitiligo should be managed by a dermatologist who has experience and can establish the diagnosis, as there are confusing white spots that mimic vitiligo. Vitiligo is characterized clinically by development of totally white macules, microscopically by complete absence of melanocytes, and medically by an increased association with certain medical diseases, particularly thyroid disease.
Causes of Vitiligo
Three principal theories have been presented about the mechanism of destruction of melanocytes in vitiligo. The autoimmune theory holds that selected melanocytes are destroyed by certain lymphocytes that have somehow been activated internally. The neurogenic hypothesis is based on an interaction of the melanocytes and the nerve cells. 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.
Symptoms of Vitiligo
People who develop vitiligo usually first notice white patches (depigmentation) on their skin. These patches are more common in sun-exposed areas, including the hands, feet, arms, face, and lips. Other common areas for white patches to appear are the armpits and groin and around the mouth, eyes, nostrils, navel, and genitals.
Vitiligo generally appears in one of three patterns. In one pattern (focal pattern), the depigmentation is limited to one or only a few areas. Some people develop depigmented patches on only one side of their bodies (segmental pattern). But for most people who have vitiligo, depigmentation occurs on different parts of the body (generalized pattern). In addition to white patches on the skin, people with vitiligo may have premature graying of the scalp hair, eyelashes, eyebrows, and beard. People with dark skin may notice a loss of color inside their mouths.
Diagnosis
Normally, diagnosis of vitiligo can be made readily on clinical examination of a patient with progressive, acquired, chalk-white, bilateral (ususally 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).
Treatment
There is a widespread perception, even among dermatologists, that vitiligo is not treatable with any method. This is regrettable, because affected patients are denied treatments that are available and effective when given by those dermatologists who can establish the diagnosis, select the option for treatment, and be persistent until the cosmetic improvement is acceptable. The duration of the vitiligo has no effect on the success of the repigmentation with PUVA photochemotherapy.
The eight aproaches in the management of vitiligo are as follows:
1. 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 of more than 30 are reasonable choices to prevent sunburn for most patients. However, since their ability to limit the tanning reaction is inversely proportional to skin phototype, opaque sunscreens should be more effective in limiting the tanning reaction in fairer-skinned individuals. While all skin phototypes have a need for sun protection, sunscreens alone are often perfectly adequate management for those vitiligo patients with skin phototypes I, II, and sometimes III (those who burn and then tan).
2. Cosmetic Coverup The objective of coverup with dyes or makeup is to hide the white macules so that the vitiligo is not apparent. Vitadye (ICN) and Dy-o-Derm (Owen Laboratories) both come in one color, 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; many contain sunscreens that are effective for much less time than the dye is present. Estee Lauder preparations have been found particularly useful by patients. Covermark (Lydia O’Leary) and Dermablend (Flori Roberts) are cosmetics available to match most skin hues; they do not wash off but do rub off. Other preparations may be found at cosmetic counters.
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.
3. Topical Glucocorticoids Initial treatment with intermittent (4 weeks on, 2 weeks off) topical Class I glucocorticoid ointments is practical, simple, and safe for single or a few macules. If there is no response in 2 months, it is unlikely to be effective. Physician monitoring every 2 months for signs of early steroid atrophy and telangiectasia is required.
4. Topical Photochemotherapy Much more complicated is the use of UVA or sunlight and topical 8-methoxypsoralen (8-MOP; this substance is highly phototoxic and the phototoxicity lasts for 3 days or more. This procedure should be undertaken for small macules only by experienced physicians and well-informed patients. As with oral psoralens, it may require 15 or more treatments to initiate response and 100 or more to finish.
5. Systemic Photochemotherapy For more widespread vitiligo, oral PUVA is more practical and carries less risk of severe phototoxicity than topical phototherapy. Oral phototherapy may be done with sunlight and 5-methoxypsoralen (5-MOP) (available in Europe) or with artificial UVA (doctor’s office or other approved unit) and 5-MOP, or 8-MOP. Ophthalmologic examination and a blood ANA test are required before starting therapy.
Outdoor PUVA therapy, when available (in summer or in areas with year-round sunlight); treatment may be initiated with 1.2 mg/kg 5MOP followed 2 h later by 5 min of sunlight(less in the southern regions). Treatments should be twice weekly, though not on two consecutive days, and sunlight exposure should increase by 3 to 5 min per treatment until a sign of response or of slight phototoxicity (i.e., redness) occurs. In some patients, mild phototoxicity is required for response, and in a few it causes koebnerization. Individualization of treatment is required. The unavailability of 5 MOP in the U.S. is a serious problem as trioxsalen is no longer available and, therefore, there is no safe treatment for vitiligo with sunlight and psoralens; 8-MOP is too phototoxic to use for outdoor vitiligo therapy. The treatment of vitiligo in the United States must be oral 8MOP plus UVA irradiators. This creates an economic problem for those patients who cannot afford the cost of UVA irradiation.
Indoor PUVA therapy is as effective as is PUVA with sunlight; it can be controlled more rigorously but has the significant disadvantage of additional cost. Either .2 to .4 mg/kg 8-MOP (Well absorbed, efficient, Potentially very phototoxic, with significant risk of nausea) 1 h before UVA exposure or 1.2 mg/kg 5-MOP (less phototoxic than 8-MOP and no nausea) 2 h before UVA exposure. Initial UVA exposure should be 1 J/cm² and increments (twice weekly, not on two consecutive days) of .5 (8MOP ) to 1 J/cm² per treatment until evidence of response or of phototoxicity appears. The latter is the guide to sustaining or increasing the UVA dose until reasonable repigmentation has been established or until progress has started in the form of tiny macules of pigmentation. When this occurs, it is a good prognostic sign for successful repigmentation.
Oral PUVA photochemotherapy with either 8-MOP or 5-MOP is up to 85% effective in more than 70% of patients with vitiligo of the head, neck, upper arms and legs, and trunk. Distal hands and feet are poorly responsive and, when present alone, are not usually worth treating. Genital areas should be shielded and not treated.
Macules that have totally repigmented usually stay that way in the absence of injury or sunburn (85% likelihood up to 10 years); macules less than fully repigmented will slowly reverse once treatments have been discontinued. Maintenance treatments are not required.
Risks of treatment with PUVA acutely include nausea, gastrointestinal upset, sunburn reaction, hyperpigmentation of the normal skin, and dryness. Chronic effects include photoaging, PUVA lentigines, keratoses (including leukokeratoses), skin cancers (we have seen 1 in more than 30 years of collective experience with more than 4000 patients), and cataracts (we have not observed any).
Standard PUVA precautions should apply; we advise against oral PUVA in children younger than 10 years of age. For children we now use narrow-band UVB 311 nm without oral psoralens and with reasonable success. Treatment is most likely to be successful in highly motivated patients who have reasonable objectives and understand the risks and benefits. While PUVA photochemotherapy is not a cure, most patients who are responding well to treatment do not at the same time develop new vitiligo macules.
6. Narrow-band UVB 311 nm This new light source, which is not available widely, appears to be effective without the use of psoralens, but there is new evidence that it is more effective when combined with oral 8-MOP. Comparative studies are in progress to quantify the addition of psoralens to UVB 311 nm and also to compare the responses to PUVA treatment for vitiligo.
7. Minigrafting Minigrafting may be a useful technique for refractory and stable segmental vitiligo macules. PUVA may be required after the procedure to unify the color between the graft sites. The demonstrated occurrence of koebnerization in donor sites in generalized vitiligo restricts this procedure to those who have limited cutaneous areas at risk for vitiligo (i.e., segmental vitiligo in which there is no koebnerization of normal skin). “Pebbling” of the grafted site may occur.
Depigmentation The objective of depigmentation is “one” skin color in patients with extensive vitiligo or in those who have failed PUVA, who cannot use PUVA, or who reject the PUVA option.
8. Bleaching Monobenzylether of hydroquinone 20% cream (monobenzone 20%) of normally pigmented skin is permanent, irreversible process. Since application of monobenzone 20% may be associated with satellite depigmentation, this treatment cannot be used selectively to bleach certain areas of normal pigmentation, since there is a real likelihood that new and distant white macules will develop over the months of use. Bleaching with monobenzone 20% normally requires the application twice daily to the body, takes 2 to 3 months to initiate response, and up to 9 to 12 months or more to complete. Erythema, dryness, and itching are possible side effects. Contact dermatitis is observed uncommonly. The success rate is over 90%. Periodically, after sun exposure, an occasional patient will observe focal repigmentation that requires a month or so of local use of monobenzone 20% to reverse; use of a sunscreen containing titanium dioxide or zinc oxide should reduce this risk.
The end-stage color of depigmentation with monobenzone 20% is chalk-white, as in vitiligo macules. Most patients are quite satisfied with the uniformity and the finality of the results. An occasional patient may wish to take 30 to 60 mg β-carotene per day to impart an off-white color to the skin; other than the color change, the only side effect of β-carotene is uncommon of diarrhea.
All those who have bleached are at risk for sunburn from acute solar irradiation. Avoidance of midday sun exposure and use of a sunscreen with a high sun protection factor are urged.
No long-term untoward effects have been reported from the use of monobenzylether of hydroquinone 20% cream. But note that the depigmentation achieved is permanent; the patient must understand this fact. With the development of a new therapy that could dramatically change the color, repigmentation will not be successful in patients who have had the melanocytes destroyed. This is especially true for those patients with a long life span such as children or young adults, as research is now being done on pathogenesis and treatment that may alter the type of therapy given, such as cytokines. Depigmented areas may repigment in the exposed areas, and bleaching should be done again.
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