[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.205.0.26. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Download PDF
Figure 1.
Mean repigmentation, expressed in percentage of surface area, in patients treated with fluticasone propionate (FP) alone, UV-A alone, vs FP and UV-A, during a 9-month period (per protocol analysis).

Mean repigmentation, expressed in percentage of surface area, in patients treated with fluticasone propionate (FP) alone, UV-A alone, vs FP and UV-A, during a 9-month period (per protocol analysis).

Figure 2.
Clinical repigmentation in a patient treated with fluticasone propionate (FP) and UV-A vs FP (A) and in a patient treated with FP and UV-A vs UV-A (B), before and after 9 months of treatment.

Clinical repigmentation in a patient treated with fluticasone propionate (FP) and UV-A vs FP (A) and in a patient treated with FP and UV-A vs UV-A (B), before and after 9 months of treatment.

Table 1. 
Characteristics of Patients (N = 135)*
Characteristics of Patients (N = 135)*
Table 2. 
Repigmentation in All Patients (N = 135) After 3 Months of Treatment*
Repigmentation in All Patients (N = 135) After 3 Months of Treatment*
Table 3. 
Repigmentation in All Patients (N = 135) After 6 Months of Treatment*
Repigmentation in All Patients (N = 135) After 6 Months of Treatment*
Table 4. 
Repigmentation After 9 Months of Treatment*
Repigmentation After 9 Months of Treatment*
Table 5. 
Success of Treatment Among All Patients (N = 135)*
Success of Treatment Among All Patients (N = 135)*
1.
Mosher  DBFitzpatrick  TBOrtonne  JPHori  Y Disorders in pigmentation. Fitzpatrick  TBEisen  AZWolff  KFreedberg  IMAusten  KFeds.Dermatology in General Medicine. New York, NY McGraw-Hill Book Co1987;810- 821
2.
Westerhof  W Pigmentstoornissen. van Vlooten  WADegreef  HJStolz  EVermeer  BJWillemze  Reds.Nederlands Leerboek voor Dermatologie en Venereologie. Utrecht, the Netherlands Bunge1992;76- 89
3.
Mishima  YKawasaki  HPinkus  H Dendritic cell dynamics in progressive depigmentations. Arch Dermatol Forsch. 1972;24367- 87Article
4.
Brostoff  J Autoantibodies in patients with vitiligo. Lancet. 1969;2177- 178Article
5.
Foley  LMLowe  NJMisheloff  ETiwari  JL Association of HLA-DR4 with vitiligo. J Am Acad Dermatol. 1983;839- 40Article
6.
Naughton  GKEisinger  MBystryn  JC Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J Invest Dermatol. 1983;81540- 542Article
7.
Bleehen  SS The treatment of vitiligo with topical corticosteroids: light and electron microscopic studies. Br J Dermatol. 1976;94 (suppl 12) 43- 50Article
8.
Ito  ATanaka  CTakeuchi  TMishima  Y Glucocorticoid stimulates melanogenesis and tyrosinase gene expression in B16 melanoma cells. Pigment Cell Res. 1991;4247- 251Article
9.
Kandil  E Vitiligo-response to 0.2% betamethasone 17-valerate in flexible collodion. Dermatologica. 1970;146277- 281Article
10.
Koopmans-van Dorp  BGoedhart-van Dijk  BNeering  Hvan Dijk  E Treatment of vitiligo by local application of betamethasone 17-valerate in a dimethyl sulfoxide base. Dermatologica. 1973;146310- 314Article
11.
Kandil  E Treatment of vitiligo with 0.1 per cent betamethasone 17-valerate in isopropyl alcohol: a double-blind trial. Br J Dermatol. 1974;91457- 460Article
12.
Kumari  J Vitiligo treated with topical clobetasol propionate. Arch Dermatol. 1984;120631- 635Article
13.
Liu  XQShao  CGJin  PYWang  HQYe  GYYawalkar  S Treatment of localised vitiligo with ulobetasol cream. Int J Dermatol. 1990;29295- 297Article
14.
Clayton  R A double-blind trial of 0.05% clobetasol propionate in the treatment of vitiligo. Br J Dermatol. 1977;9671- 73Article
15.
Stevanovic  DV Corticosteroid-induced atrophy of the skin with teleangiectasia: a clinical and experimental study. Br J Dermatol. 1972;87548- 556Article
16.
Carruthers  JAAugust  PJStaughton  RC Observations on the systemic effect of topical clobetasol propionate (Dermovate). BMJ. 1975;4203- 204Article
17.
Lebwohl  M Efficacy and safety of fluticasone propionate ointment, 0.005%, in the treatment of eczema. Cutis. 1996;57 (suppl 2) 62- 68
18.
Spencer  CMWiseman  LR Topical fluticasone propionate: a review of its pharmacological properties and therapeutic use in the treatment of dermatological disorders. BioDrugs. 1997;7318- 334Article
19.
Juhlin  L Comparison of fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.01%, in the treatment of eczema. Cutis. 1996;57 (suppl 2) 51- 56
20.
Pathak  MA Effect of UV-A, UV-B and psoralen on in vivo human melanin pigmentation. Pigment Cell. 1976;3291- 298
Study
September 1999

Left-Right Comparison Study of the Combination of Fluticasone Propionate and UV-A vs Either Fluticasone Propionate or UV-A Alone for the Long-term Treatment of Vitiligo

Author Affiliations

From the Netherlands Institute for Pigmentary Disorders (Drs Westerhof and Nieuweboer-Krobotova), and Department of Dermatology, Academic Medical Centre (Dr Westerhof), Amsterdam; Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam (Dr Mulder); and Medical Department, Glaxo Wellcome BV, Zeist (Mr Glazenburg), the Netherlands.

Arch Dermatol. 1999;135(9):1061-1066. doi:10.1001/archderm.135.9.1061
Abstract

Objective  To compare the efficacy and safety of using a combination of fluticasone propionate (FP) and UV-A with that of either drug used alone in the long-term treatment of vitiligo.

Design  Prospective, randomized, controlled, left-right comparison study. Repigmentation was judged by a single dermatologist (L.N.-K.) and skin thickness was scored by a pathologist (using biopsy samples), a dermatologist (L.N.-K.) (visually), and patients (using a standard questionnaire).

Setting  Netherlands Institute for Pigmentary Disorders, Amsterdam.

Patients  Patients with lesions on arms, legs, and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A (FP group) or with UV-A alone and a combination of FP and UV-A (UV-A group). Fluticasone propionate cream was applied once daily at about bedtime, and UV-A (10 J/cm2) exposure was twice a week. Patients attended the clinic at 3-month intervals.

Results  One hundred thirty-five patients were included, 96 of whom were evaluable after 9 months. Patients not reaching the end point withdrew because of insufficient repigmentation (n=23), decreased motivation (n=11), or protocol violations (n=5). No patient (irrespective of whether they withdrew) experienced any adverse effects. The FP and UV-A groups were comparable with respect to sex, age, and location of lesions. On average, combination treatment was 3 times more effective than either UV-A or FP treatment alone. In the FP group, no atrophy was seen after 9 months with either treatment. In the UV-A group, a little atrophy was detected twice: as well during UV-A treatment alone as during combination treatment.

Conclusions  Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone, but large interindividual differences occur. Fluticasone propionate, UV-A, and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo.

VITILIGO IS an acquired pigmentary skin disorder, often with a progressive course. Much about the cause of vitiligo remains uncertain. It is possible that autoimmune mechanisms are involved in its pathogenesis, as an increased incidence of autoantibodies has been found in patients with vitiligo.1,2 Furthermore, vitiligo is often associated with autoimmune diseases such as thyroid diseases and diabetes mellitus. Another indication that vitiligo may be an autoimmune disease is the fact that antibodies to melanocyte-associated antigens have been found in patients with vitiligo and correlate with disease activity.3,4 Involvement of cellular immunity has been considered because T lymphocytes and macrophages in perilesional skin have been reported frequently.5,6

Topical corticosteroids can be effective in the treatment of vitiligo.7,8 It is well-known that use of corticosteroids has an immunosuppressive effect. If vitiligo has an autoimmune pathogenesis, this could explain why the disease process stops when applying corticosteroids, thereby allowing melanocyte repopulation spontaneously or by UV irradiation. Repopulation of the epidermis with functional melanocytes in treated areas starts around hair follicles and appears as perifollicular islands of pigment that gradually coalesce. Also, a gradual spread of pigment from the margins of vitiligo lesions to the center takes place. Repigmentation has been shown to continue for 2 to 4 months after cessation of treatment.

Repigmentation depends on the potency of the corticosteroid used.7 Use of a moderately potent corticosteroid often has little or no effect, whereas use of a very potent corticosteroid results in considerable repigmentation.914 However, use of especially potent and very potent corticosteroids can cause serious adverse effects, the most significant of which is dermal atrophy. In several trials,12,15 most patients showed dermal atrophy when strong corticosteroids were used for a long time. Furthermore, percutaneous absorption of potent and very potent corticosteroids has been reported to lead to suppression of the pituitary-adrenal axis.16 Because repigmentation is a long-term process, and because of these well-known serious adverse effects of corticosteroid treatment, controlled long-term studies on repigmentation with potent corticosteroids have not been conducted.

Fluticasone propionate (FP) is a recently developed topical corticosteroid with high anti-inflammatory therapeutic efficacy yet minimal potential to cause unwanted adverse effects.1719 Based on its favorable efficacy-safety ratio, FP could be of use in the long-term treatment of vitiligo. Its efficacy could lead to satisfying repigmentation, and its safety profile (with respect to local and systemic adverse effects) is unique for a corticosteroid of its strength.

Preliminary experiences with the use of different corticosteroids have shown that topical corticosteroids can have a positive effect on repigmentation but that this repigmentation is sometimes restrictive and often disappointing. However, when topical application of corticosteroids was combined with UV-A irradiation several times a week, a longer-lasting and more obvious result of the therapy was observed (W. W., unpublished data, 1989). This could be because the most important factor in stimulating human melanocyte proliferation and migration is formed by exposure to UV radiation. Repeated multiple exposures to UV-A or UV-B radiation result in a marked increase in the number and functional state of active melanocytes.20 This possible synergistic effect of combination therapy in patients with vitiligo has never been formally investigated or described.

We performed a randomized, controlled, left-right comparative study of FP in combination with UV-A vs FP or UV-A alone in the treatment of vitiligo. By using a left-right comparison, fewer patients are needed and can form their own controls. This is important because individual patients differ in their response to therapy. It is therefore not necessary to use a different group of untreated patients with vitiligo.

PATIENTS AND METHODS
STUDY POPULATION

This randomized, controlled, left-right comparative study included 135 patients with vitiligo, based on the following criteria: aged 18 to 80 years; vitiligo with long-term stable or active lesions; 2 (almost) equal symmetrical lesions on arms, legs, or trunk; and no spontaneous repigmentation. Exclusion criteria were vitiligo on the face, hands, or feet only; use of immunosuppressive agents; use of topical corticosteroids in the 2 weeks before study initiation; use of systemic corticosteroids in the 6 weeks before study initiation; known hypersensitivity to FP or abnormal reactions to UV-A radiation; signs of skin atrophy; and pregnancy.

The study protocol was approved by the medical ethics committee at the Academic Medical Centre, Amsterdam, the Netherlands, and all patients provided written informed consent.

STUDY DESIGN AND METHODS

Patients were treated for 9 months on 2 symmetrical lesions, 1 with FP cream alone and the other with FP and UV-A (FP group), or 1 with UV-A alone and the other with FP and UV-A (UV-A group). The FP cream was applied every evening, half an hour before going to bed; UV-A (10 J/cm2) exposure was twice a week, and each session lasted 20 minutes. We used a cream containing 0.05% FP (Cutivate; Glaxo Wellcome B.V., Zeist, the Netherlands) and a UV-A facial tanner (HB 171 or HB 181, Philips B.V., Eindhoven, the Netherlands). Power output of these facial tanners was as follows: HB 171-UV-A, 80 W/m2; UV-B, 0.9 W/m2; and effective energy, 0.14 W/m2. HB 181-UV-A, 100 W/m2; UV-B, 1.1 W/m2; and effective energy, 0.17 W/m2.

Vitiligo was assessed, symmetrical lesions were chosen, and patients were randomized to 1 of the 2 treatment arms (FP or UV-A group) at the start of the study. A baseline black-and-white photograph was taken of both lesions (UV-filter Schott UG1 for UV photography and B+W Filterfabrik; Johannes Weber GMBH & Co, Bad Kreuznach, Germany).

At clinic visits at 3, 6, and 9 months, repigmentation (expressed in percentages: 0% indicates no repigmentation; 75%, significant and satisfying repigmentation; and 100%, complete repigmentation) was assessed by a single dermatologist (L.N.-K.), and visual scoring of the skin with respect to thickness, striae, telangiectasis, acne, hypertrichosis, and allergic reactions was performed. At every visit, a control photograph of both lesions was taken. At the end of the study, 3 skin biopsy samples were taken (1 from each lesion and 1 control, mostly from the hip).

Throughout the study, patients gave their opinions about the effects and adverse effects of their treatment by answering a standard questionnaire, which asked whether the UV-A irradiation caused any adverse effects such as redness, dry skin, or itching (possible answers: no, slightly, or yes). Besides standard answers on these scales, patients could express their opinions about the condition of their skin by commenting on each question.

RESULTS
PATIENT DEMOGRAPHICS

Of 135 patients included in the study, 67 were randomized to the FP group and 68 to the UV-A group. After 9 months, 96 patients were evaluable: 44 in the FP group and 52 in the UV-A group. Patients in both groups were comparable with respect to sex, age, and location of lesions and had active vitiligo; no patient had vitiligo in combination with other autoimmune disorders.

In the FP group, 23 patients did not reach the end point because of insufficient repigmentation in their opinion (n=12, most withdrew between 3 and 6 months of treatment), decreased motivation (n=7, in their opinion, treatment, especially irradiation with UV-A, took too much time, and most withdrew during the first 3 months of treatment), and violation of the protocol (exposure of study lesions to sunlight, n=4).

In the UV-A group, 16 patients prematurely withdrew from the study for the same reasons as above (n=11, 4, and 1, respectively). No patient in either group withdrew because of atrophy or adverse effects.

Baseline vitiligo characteristics of all patients are summarized in Table 1.

TREATMENT OUTCOME

After 3 months of treatment, percentages of repigmentation with FP alone and UV-A alone were comparable, with no statistically significant difference (P=.61) between them. Combination treatment with FP and UV-A demonstrated a significantly higher percentage of repigmentation (P<.001, intention-to-treat analysis, Wilcoxon matched-pairs signed rank test, all patients for whom no repigmentation percentages were available received 0%) in both treatment groups than did either therapy used alone (Table 2). Results of the per protocol analysis were comparable (P<.001, results not shown). Of 44 evaluable patients in the FP group, 22 showed higher percentages of repigmentation with combination FP and UV-A treatment than with FP treatment alone, 4 had equal percentages, and 18 did not show any repigmentation in either treatment arm. In no patient did FP treatment alone result in higher percentages. Of 52 patients in the UV-A group, these numbers were 24, 3, 25, and 0, respectively.

These results were confirmed by the percentage of repigmentation seen after 6 months. Again, results of treatment with FP and UV-A alone were comparable but significantly lower (P<.001, intention-to-treat analysis) than with a combination of treatments (Table 3). Per protocol analysis confirmed these results (P<.001, results not shown). After 6 months, 28 patients in the FP group showed higher percentages of repigmentation with use of a combination of FP and UV-A, 2 had equal percentages, and 13 did not show any repigmentation; in 1 patient, FP treatment alone resulted in a higher repigmentation percentage than did the combination treatment (95% vs 80%). Results for the 52 patients in the UV-A group were 31, 2, 19, and 0, respectively.

At the end of the study (9 months), treatment with FP or UV-A alone still resulted in comparably low-percentage repigmentation rates. The combination of FP and UV-A in both treatment groups again resulted in significantly higher percentages of repigmentation (Table 4). Further analysis of the data revealed that of 44 patients in the FP group, 28 had a higher repigmentation percentage using the combination treatment, 2 had equal percentages, and 13 did not show any repigmentation in either treatment arm. Furthermore, in the same patient as after 6 months of study, treatment with FP alone resulted in a higher repigmentation percentage compared with the combination treatment (100% vs 95%). Values for the UV-A group were 26, 6, 20, and 0, respectively.

Comparison of mean repigmentation in the 2 groups during the study, as calculated by per protocol analysis, is shown in Figure 1. Photographic examples of changes in repigmentation in patients in either treatment group are depicted in Figure 2.

There was no significant difference in success of treatment when different sites were compared. During this study, in both groups, vitiligo spots on the thigh, ankle, knee, abdomen, elbow, armpit, groin, back, chest, and hollow of the knee were treated (dependent on symmetry within the patient population). None of these locations showed any preference for any treatment.

Success of the treatments, defined as a repigmentation percentage greater than 75%, is shown in Table 5. Again, combination treatment with FP and UV-A showed significant advantages compared with either treatment alone. In the UV-A group, combination treatment with FP and UV-A resulted in 6 patients with a repigmentation percentage of 95% or more (indicating complete repigmentation for the human eye, only on UV photography can tiny white spots sometimes be seen); in the FP group, 7 patients had this repigmentation percentage, also after receiving combination therapy. Treatment with UV-A or FP alone in this subgroup of patients resulted in repigmentation percentages between 0% and 95%, indicating once more the superiority of combination treatment with UV-A and FP compared with separate treatments.

Careful visual examination of skin revealed no significant atrophy or atrophogenic changes throughout the 9-month study. No patient indicated any change in skin characteristics during either treatment alone or combination therapy.

In the FP group, no evidence of any epidermal or dermal atrophy was seen in skin biopsy samples after 9 months of either treatment. In the UV-A group, a light atrophy was detected twice, as well in the lesion treated with UV-A alone, as in the symmetrical lesion treated with the combination of FP and UV-A.

COMMENT

Results of this study indicate that combination therapy with FP and UV-A can have a beneficial effect on the process of repigmentation. The ultimate result varies between no demonstrable efficacy (no signs of melanocyte proliferation) and 100% efficacy (complete return of pigment). The outcome of our study clearly shows that applying FP or exposure to UV-A alone is inferior to a combination treatment of FP and UV-A, which seems to be synergistic.

Large interindividual differences occurred, and a proportion of patients did not respond to the combination regimen. Based on these results, it can be predicted that after 3 months of treatment with the combination of FP and UV-A, about 50% of patients will show some repigmentation. This positive reaction may increase to about two thirds of the group when treatment is extended to 9 months. One can speculate that patients who show no evidence of repigmentation after 3 months of treatment may not show any benefit if this treatment is continued. Repigmentation that starts after 3 months seems unlikely to produce satisfactory results. All patients ultimately showing repigmentation of 75% and more after 9 months (in practice these patients were satisfied with their treatment) already had significant detectable repigmentation after 3 months.

In this study, it was not possible to show any relationship between patient age, skin color, disease duration, or lesion site and the repigmentation process. However, poorly repigmenting areas such as hands and feet were excluded from this study. On the other hand, the face, which is known to repigment fairly well, was also excluded.

It remains to be known why certain patients did not react at all, especially to the combination treatment. One reason for this apparent nonresponding could be that the process leading to vitiligo worsened during treatment, resulting in no repigmentation. Another possibility is that the period of UV-A irradiation in some patients was too short. Indeed, a few bad responders showed better repigmentation percentages when irradiation time was prolonged by a few minutes. Although exact instructions about application and irradiation were given at the start of the study (both verbally and written) and patients were asked at every visit if they had succeeded in following the treatment regimen, it remains possible that patient compliance was not optimal in a few patients.

Despite the large interindividual differences between patients, with some showing no or little benefit from the regimen, it could be worthwhile to apply such a combination treatment in vitiligo because the combination can be tried without fear of the adverse effects that long-term use of corticosteroids sometimes causes. Long-term daily application of FP to the same site for 9 months did not result in any local adverse effects in this population. These are surprising data because FP is a class III corticosteroid, and the common opinion is that daily use of this class of corticosteroids will cause problems when used for longer periods.

The overall conclusion of our study is that combination treatment with FP and UV-A can be effective in reaching complete repigmentation but that large interindividual differences occur. Combination treatment is much more effective than the sum of each separate treatment. UV-A, FP, and a combination of FP and UV-A are safe in the long-term treatment of vitiligo.

Back to top
Article Information

Accepted for publication April 14, 1999.

This study was supported by a grant from Glaxo Wellcome BV, Zeist, the Netherlands.

Reprints: Wiete Westerhof, MD, PhD, the Netherlands Institute for Pigmentary Disorders, Meibergdreef 35, 1105 AZ Amsterdam, the Netherlands (e-mail: w.westerhof@amc.uva.nl).

References
1.
Mosher  DBFitzpatrick  TBOrtonne  JPHori  Y Disorders in pigmentation. Fitzpatrick  TBEisen  AZWolff  KFreedberg  IMAusten  KFeds.Dermatology in General Medicine. New York, NY McGraw-Hill Book Co1987;810- 821
2.
Westerhof  W Pigmentstoornissen. van Vlooten  WADegreef  HJStolz  EVermeer  BJWillemze  Reds.Nederlands Leerboek voor Dermatologie en Venereologie. Utrecht, the Netherlands Bunge1992;76- 89
3.
Mishima  YKawasaki  HPinkus  H Dendritic cell dynamics in progressive depigmentations. Arch Dermatol Forsch. 1972;24367- 87Article
4.
Brostoff  J Autoantibodies in patients with vitiligo. Lancet. 1969;2177- 178Article
5.
Foley  LMLowe  NJMisheloff  ETiwari  JL Association of HLA-DR4 with vitiligo. J Am Acad Dermatol. 1983;839- 40Article
6.
Naughton  GKEisinger  MBystryn  JC Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J Invest Dermatol. 1983;81540- 542Article
7.
Bleehen  SS The treatment of vitiligo with topical corticosteroids: light and electron microscopic studies. Br J Dermatol. 1976;94 (suppl 12) 43- 50Article
8.
Ito  ATanaka  CTakeuchi  TMishima  Y Glucocorticoid stimulates melanogenesis and tyrosinase gene expression in B16 melanoma cells. Pigment Cell Res. 1991;4247- 251Article
9.
Kandil  E Vitiligo-response to 0.2% betamethasone 17-valerate in flexible collodion. Dermatologica. 1970;146277- 281Article
10.
Koopmans-van Dorp  BGoedhart-van Dijk  BNeering  Hvan Dijk  E Treatment of vitiligo by local application of betamethasone 17-valerate in a dimethyl sulfoxide base. Dermatologica. 1973;146310- 314Article
11.
Kandil  E Treatment of vitiligo with 0.1 per cent betamethasone 17-valerate in isopropyl alcohol: a double-blind trial. Br J Dermatol. 1974;91457- 460Article
12.
Kumari  J Vitiligo treated with topical clobetasol propionate. Arch Dermatol. 1984;120631- 635Article
13.
Liu  XQShao  CGJin  PYWang  HQYe  GYYawalkar  S Treatment of localised vitiligo with ulobetasol cream. Int J Dermatol. 1990;29295- 297Article
14.
Clayton  R A double-blind trial of 0.05% clobetasol propionate in the treatment of vitiligo. Br J Dermatol. 1977;9671- 73Article
15.
Stevanovic  DV Corticosteroid-induced atrophy of the skin with teleangiectasia: a clinical and experimental study. Br J Dermatol. 1972;87548- 556Article
16.
Carruthers  JAAugust  PJStaughton  RC Observations on the systemic effect of topical clobetasol propionate (Dermovate). BMJ. 1975;4203- 204Article
17.
Lebwohl  M Efficacy and safety of fluticasone propionate ointment, 0.005%, in the treatment of eczema. Cutis. 1996;57 (suppl 2) 62- 68
18.
Spencer  CMWiseman  LR Topical fluticasone propionate: a review of its pharmacological properties and therapeutic use in the treatment of dermatological disorders. BioDrugs. 1997;7318- 334Article
19.
Juhlin  L Comparison of fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.01%, in the treatment of eczema. Cutis. 1996;57 (suppl 2) 51- 56
20.
Pathak  MA Effect of UV-A, UV-B and psoralen on in vivo human melanin pigmentation. Pigment Cell. 1976;3291- 298
×