VITILIGO, an unpredictable disease
By Dr. Giovanni Leone Dr. Andrea Paro Vidolin – Specialist in Dermatology and Venereology – Columbus Clinic Center
Vitiligo is an acquired skin disorder characterized by pale white and depigmented well-limited, uniform patches. The edges of the patch may be irregular, yet always clearly visible. Occasionally, a hyperpigmented margin is seen. The surface is normal (there is no atrophy or hyperkeratosis) ) except for the pigmentary alterations which may also affect the color of hair. Men and women are equally affected with an incidence of 0.5-2% of the world population.
Vitiligo can start at any age, but in 50% of cases it appears between age 10 and 30.
The natural course of the disease is unpredictable; it can remain dormant for years or start progressing very quickly. Psycho-affective or physical traumas are sometimes reported as trigger events. Sunlight exposure and UV rays do not trigger the condition; instead, they reveal it by accentuating the contrast between the affected skin, where pigmentation does not occur, and the normal one, which becomes pigmented.
Based on the distribution and extension of lesions, there are two types of vitiligo: generalized and localized vitiligo.
The former is the most common type and affects multiple skin areas symmetrically and bilaterally.
Localized vitiligo, on the other hand, affects one particular area of the body. The achromic macules can exhibit a focal distribution, if the patches appear randomly, or segmental, when they are distributed along one or several dermatomes.
Diagnosis is easy to confirm and the intensity of depigmentation is assessed by comparison with the surrounding normal skin in localized vitiligo cases and with the skin of parents when the entire integument is affected. Sometimes, however, it is difficult to identify slightly hypopigmented lesions in fair-skinned patients; in these cases, Wood’s lamp examination is a useful diagnostic test. Examination by Wood’s light must be carried out on every subject showing an alteration of pigmentation; in fact, in the case of hypopigmented lesions, Wood’s light accentuates the contrast between lesional skin and normal skin.
THE THERAPEUTIC CHOICE
First of all, the treatment must be planned in relation to the extension of the lesions: if vitiligo covers less than 10% of the body surface area, topical steroids can be used as a first therapeutic attempt.
Phototherapy or photochemotherapy (PUVA), instead, seems to serve well as a first-line therapy for a more extended diffusion range.
For some particular areas that are poorly responsive to phototherapy treatment (hands, feet), or when special requirements exist, it is possible to opt for melanocytes transplantation.
Proposed treatments for generalized vitiligo, in which lesions tend to spread rapidly, include doses of systemic corticosteroids, which would be able to stop the condition spreading. However, it seems that the disease relapses when treatment is stopped.
With affected areas of more than 70-80% of the body surface, definitive depigmentation of the normally pigmented skin with monobenzyl ether of hydroquinone in a 20% concentration can be attempted. This treatment is long and can cause skin sensitisation reactions.
Medium-high potency topical corticosteroids can be used for the treatment of very localized forms of vitiligo and for younger children who cannot be treated with phototherapy. Treatment with topical steroids can be continued for 1-2 months and patients must be kept under strict surveillance in order to identify possible side effects as soon as possible.
Recent studies have shown the efficacy of topical tacrolimus in localized vitiligo. The methods of use and therapeutic effects appear to be similar to those of topical steroids.
Phototherapy has always been one of the most effective therapeutic approaches in the treatment of vitiligo, a disease in which therapeutic attempts are often made on an empirical basis. The effectiveness of phototherapy is based on the possibility of stimulating the production of pigment in areas of skin affected by vitiligo, thus repopulating the epidermal areas devoid of melanocytes favouring their migration from healthy perilesional skin and from the hair follicle “reservoir”. The stimulus is represented by ultraviolet radiation, whether or not associated with the systemic or topical administration of photosensitizing drugs. Heliotherapy has provided inconsistent results, as well as broad-band UVB phototherapy (conventional UVB). With the introduction of PUVA therapy in the 1970s, this was also used in vitiligo treatment.
PUVA therapy in vitiligo cases
Until a few years ago, PUVA was the first-line phototherapy treatment option for this condition. Currently, in order to avoid the side effects caused by the oral intake of psoralen, when it is possible and required, we tend to use narrow-band (TL01) UVB phototherapy.
PUVA therapy can be administered either by exposing the patient (after oral intake of psoralen) to an artificial source of UVA, or to sunlight (PUVASol, heliotherapy). The latter has been in use for some years now, but must be discouraged as the dose of UVA received during solar exposure cannot be precisely controlled, with the risk of violent phototoxic reactions.
Based on the theory that in vitiligo there is damage to melanocytes induced by free radicals and reactive oxygen species (ROS), that is, an “oxidative stress”, we have proposed treatments with integrated oral antioxidants.
Although the skin has an efficient and varied antioxidant network, many oxidizing substances can escape the system and cause critical damage, especially in cases where the defence mechanisms are faced with overloads.
It is worth noticing that antioxidant mixtures have been shown to be more effective systemically than individual active substances, which demonstrates the need for supplementation to be integrated into the complex system of the physiological antioxidant pool. Based on these assumptions, we have used various antioxidant mixtures containing: beta-carotene, vitamin C, vitamin E, as well as L-tyrosine, L-cysteine and other useful nutrients for melanin synthesis. It is possible to add micronutrients such as selenium, copper and zinc.
Against this background and following the positive results we have obtained in vitiligo with the sole administration of systemic antioxidants, we have started studies involving the association of antioxidants with narrow-band UVB phototherapy. In addition to the scavenger effect on free radicals, which seems to positively influence the evolution of vitiligo, it cannot be excluded that there is also a photoprotective effect attributed to the administration of antioxidants, which increases the erythemal threshold, and reduces inflammatory phenomena following UV exposure. In this way, the narrow-band UVB phototherapy would also be better tolerated and the dosage could be increased with greater confidence. In addition to the antioxidant mixture, it seems useful to associate, in the specific case of vitiligo, those nutrients and trace elements which are likely to have a positive role in the melanin formation process, in particular: L-tyrosine, L-cysteine, copper, zinc, vitamin B2 (Riboflavin) and vitamin D3. In conclusion, all these substances stimulate the conversion of tyrosine to dihydroxyphenylalanine, thus facilitating the task of tyrosinase. Tyrosine is well known for the fundamental role played in the pathway leading to the synthesis of melanin; therefore, an adequate supply of this essential amino acid helps to enhance the pigmentogenic response following ultraviolet irradiation.
Some private practices propose “targeted” therapies based on the use of ultraviolet light on very small areas of skin. These treatments allow to avoid irradiating skin areas which are not affected by vitiligo.
Studies published in recent years have demonstrated the efficacy of two new phototherapeutic sources: the monochromatic excimer light and the 308-nm excimer laser for the treatment of Vitiligo. These two sources allow to selectively irradiate Vitiligo patches while sparing the surrounding normally pigmented skin.
The wavelength of the laser and of the excimer light is always a narrow-band 308 nm UVB light, but there is a non-coherent emission of light (in fact, it is not a laser in the strict sense of the term).
Thanks to the emission of a powerful monochromatic, coherent and collimated beam, the 308-nm excimer laser allows rapid treatments and early induction of repigmentation after only 10 sessions. Patients do not feel anything during the treatment except a transient sensation of heat, which makes this method perfectly tolerable