Journal of the European Academy of Dermatology and Venereology 12 (1999) 1-7

Original article

UV-B radiation microphototherapy. An elective treatment for segmental vitiligo.

Torello M. Lotti*, Lucio Andreassi**.

*Department of Dermatology, University of Florence, Florence, Italy
**Department of Dermatology, University of Siena, Siena, Italy

 

Background: Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation. Previous studies have suggested the effectiveness of UV-B radiation in generalized vitiligo (GV) therapy, but there was no evidence to support the same role for segmental vitiligo (SV).

Objective: The purpose of this study was to use UV-B radiation exclusively on vitiligo patches of individuals affected by SV to evaluate the effectiveness of this therapy.

Subjects & Methods: 8 individuals with SV were treated for six months with a new device called BIOSKIN ® that can produce a focused beam of UV-B (microphoto-therapy) on vitiligo patches only. Photographs of the subjects were taken at the beginning of the therapy and once a month thereafter for six months. The response to treatment was estimated in 2 comparable photographs using planimetry. A control group of 8 individuals matched for sex and age was treated with placebo, using the same device but not releasing any kind of detectable light.

Results: After six months of microphototherapy 5 subjects of the 8 studied achieved normal pigmentation on more than 75% of the treated areas. In particular, 3 of these were totally repigmented. Two individuals achieved 50-75% pigmentation of the treated areas, and only one showed less than 50% repigmentation (table 3). In the control group only one patient showed moderate repigmentation (less than 50%) (table 3) (Figure 1).

Conclusion: UV-B microphototherapy seems highly effective in restoring pigmentation in patients affected by vitiligo. As no side effects have been observed, this could represent the treatment of choice in the limited (segmental) forms of vitiligo.

Keywords: vitiligo, UV-B, therapy

 

Introduction

Vitiligo is an acquired hypomelanotic disease of unknown etiology affecting 1-2% of world population without any racial, geographic or sex differences (1). Although use of ultraviolet-B (UV-B) radiation in vitiligo therapy is relatively recent, it is considered presently the most effective treatment for generalized vitiligo (1,2).

The successful use of UV-B rays is probably due to several direct and mediated interactions of UV-B with melanocytes, keratinocytes and skin immune system (Table 1).

Enhancement of pigmentation -  By increase of melanocyte stimulating hormone (MSH) receptor binding activity and melanocortin receptor gene expression [3] - By activation of cyclic-AMP pathway by alpha-melanotropin which increases melanocyte proliferation and melanogenesis [4] - By irradiated keratinocyte production of nitric oxide (NO) (paracrine induction of melanogenesis) [5] - By increase of tyrosinase mRNA expression and enzymatic activity  [6] - By melanocyte production and secretion of corticotropin releasing factors  [7] lnduction of skin inflammation - By enhancement of keratinocyte production and release of TGFß-1  [8] - By enhancement of keratinocyte production and release of IL-1  [9] Alteration of local (skin) immune system response - By enhancing production and release of TGFß-1which causes immunosuppression  [8] - By enhancing release of cis urocanic acid (cis-UCA)  [10] By enhancing keratinocyte production and release of TNFß  [11] Tumor promotion - By induction of c-jun and c-fos protooncogene transcription in keratinocytes [12] - By causing cellular DNA damage Cellular programmed self destruction - By increasing keratinocyte levels of tumor suppressor gene p53 [13,14] - By increasing keratinocyte Ievels of 1.25 dihydroxyvitamin D3, TGFß-1,Ca 2+   [15] Metabolic alteration - Enhanced production of free radical levels - Enhanced superoxid dismutase (SOD) levels and activity  [16]

Table 1 - The main direct and mediated effects of UV-B irradiation of the skin

In this study we used a new device called BIOSKIN^® provided with a focused beam of UV-B adapted to treat selected areas of depigmented skin.

Subjects and Methods

Subjects

Subjects with segmental vitiligo were included in the study after obtaining informed consent to ensure that the procedure of microphototherapy had been fully explained. The individuals were 4 men and 4 women with a mean age of 17.9 years and skin type III for 6 persons and II for the other 2. The control group was composed of 8 individuals, 5 men and 3 women, affected by SV with a mean age of 22.9 years; skin type was III for 5 persons and II for the other 3.

Table 2 shows the sex, age, Fitzpatrick skin phototype and affected areas for each subject treated.

Table2 – Sex, age, Fitzpatrick’s skin phototype and affected areas for each subject.

 

Method

BIOSKIN^® device

Bioskin device is a generator of UV-B radiation composed of three main components:

1. UV-B short arc mercury lamp (100 Watt) which generates UV-B with a spectrum of 280 to 320 nm with a maximum emission peak at 311 nm;
2. Specialized liquid component optical fiber which can transmit and focalize the emitted UV-B in a circular beam 1 cm in diameter.
3. Computerized system which allows the regulation of the intensity (10-100 mJ/cm²/s) and time of single spot emission (0.1-10 seconds).

Light spot.

Each single spot produces an energy of 10-100 mJ/cm² on a 1 cm diameter circular area (0.785 cm²) for the time necessary to reach the optimal dose. The optical fiber terminal is in contact with a different site of the treated patch during the emission of each spot. Repetition of single spots make it possible to treat VP areas completely while avoiding normal skin. Complete treatment of a 10 cm² diameter vitiligous area with 100 mJ requires repeating a 2 second 1 cm² diameter spot 6 times with 100 mJ/cm² intensity.

Treatment session

Each treatment session consists of irradiation of the VP with a dose 20% lower than minimal erythema dose (MED) calculated by the operator before the session. The length of each session depends on the length of the single light spot and the extension of the VP areas.

Treatment.

The MED in VP is evaluated 24 hours before the beginning of therapy. The subjects are treated with the following scheme:

• 5 sessions, one a day for 5 consecutive days.
• 10 days break.
• 1 session every 15 days for 5 months.

The control subjects were treated with the same protocol but with the UVB generator off. It was impossible for the control subjects to know if the generator was on or not.

Table 3 shows the MED for each patient, dose per session for cm², total dose given each subject per cm² and the final results.

Table 3 – Minimal erythema dose (MED) for subject, UVB dose per session per cm2, total dose of UVB received by affected subjects and percentage of repigmentation after active and placebo treatments (controls). *Cumulative dose = Session dose * n° of sessions

 

Photographs of the subjects were taken at the beginning of the therapy and then once a month for six months using Wood’s lamp. One month after the treatment was finished, the results were evaluated by planimetry based on two comparable photographs.

Results.

The MED of lesional skin was between 200 and 500 mJ/cm². In general repigmentation started 1 month after the beginning of the UV-B microphoto-therapy.

After 5 months 5 subjects responded with more than 75% repigmentation (3 achieved 100% repigmentation), 2 individuals showed 50-75% repigmentation and one showed repigmentation in less then 50% of the area treated.

No adverse effects were noted. The compliance was excellent. No pain or burning or itching sensations were reported by the subjects. Vitiligo was not aggravated in any subject. The average cumulative UV-B dose with the treatment was 5.025 J/cm² (range 2.4-6 J/cm²) per subject.

Comments.

According to the principles of evidence-based medicine, meta-analysis of all relevant studies in the literature recently showed that the highest mean success rates in repigmentation of vitiligo were achieved with narrow band UV-B, followed by broadband UV-B and oral methoxsalen plus UV-A therapy (2). The same study showed that oral methoxsalen plus UV-A was associated with the highest rates of side effects, while no side effects were reported with UV-B therapy (2). Thus, following the recommendations of Njoo et al based on the meta-analysis of the literature, it seems that when patients exhibit generalized vitiligo, UV-B (narrow band or broad band) therapy or, as a second choice, oral methoxsalen plus UV-A, should be recommended. For patients with localized vitiligo (defined as vitiligo affecting less than 20% of the total body surface) (2) a class 3 corticosteroid is advised as first choice therapy (2).

On the basis of the present study carried out with a novel device allowing limited and focused UV-B photoradiation, we suggest that UV-B therapy limited only to the vitiligo patches could be considered the first-choice therapy for patients with localized vitiligo, although more studies will be necessary to confirm the good results and establish the entity of possible long-term side effects. The protocol for the use of focused UV-B therapy here presented show that the therapy need not be continuous and that the cumulative UV-B doses received by the single patient with the BIOSKIN^® device is obviously much lower than the cumulative UV-B dose received by the previously established UV-B treatment intended to treat the whole, or at least a considerable part, skin surface independent of the percentage of affected skin. It is implicit that therapy limited to the vitiligo patches carries substantially less risk for skin cancer that any other kind of systemic photoradiation, with or without oral intake of psoralen.

a	b		a	b
Picture 1: A subject affected by segmental vitiligo at the beginning of microphototherapy (a: normal light, b: Wood’s light)			Picture 2: Same subject after 4 months of microphototherapy (a: normal light, b: Wood’s light). The patch of vitiligo is reduced by more than 90%.

Finally it has been observed that only well-motivated, highly compliant patients are suitable for photoradiation (2). A possible explanation is that this could depend not only on the exhausting photo(chemio) therapeutic algorithms, but also on the fact that systemic irradiation, even when successful, always provokes transient darkening of the non-affected skin, with a negative psychological impact related to the increased chromatic difference with the vitiligo patches. Instead, as repigmentation obtained with the focused UV-B microphototherapy is limited to the treated vitiligo areas and the radiation is performed only once or twice per month, the novel phototherapy treatment is extremely well accepted by the vitiligo patients.

Follow-up studies are needed to ascertain whether the repigmentation induced by this limited irradiation method is permanent.

Figure 1 Repigmentation after microphototherapy on actively treated subjects and controls.

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