|Year : 2016 | Volume
| Issue : 1 | Page : 11-16
Study of efficacy of phototherapy (psoralen with ultraviolet A and narrow-band ultraviolet B) in vitiligo
Aparna Vijay Gaikwad, Pravin R Bharatia
Department of Dermatology, K.E.M. Hospital, Pune, Maharashtra, India
|Date of Web Publication||17-Jun-2016|
Dr. Aparna Vijay Gaikwad
Department of Dermatology, K.E.M. Hospital, Rasta Peth, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Vitiligo is the most common depigmenting disorder. It is more significant in the dark-skinned population, with a major impact on the quality of life of patients. Phototherapy has been the mainstay of treatment for a long time. Both psoralens with ultraviolet A (PUVA) and narrow-band ultraviolet B (NB-UVB) therapy have shown satisfactory results. Aims: To study the efficacy of phototherapy (PUVA and NB-UVB) in patients with vitiligo and to compare the response to phototherapy (PUVA vs. NB-UVB) in vitiligo. Methods: This is a prospective study of 60 patients recruited from the patients attending the dermatology outpatient department of KEM Hospital, Pune. Thirty patients each were randomly allotted to either PUVA or NB-UVB group. Therapy was given thrice a week for PUVA and twice a week for NB-UVB on nonconsecutive days. Patients were followed-up every month for 1 year. Two primary parameters, repigmentation and arrest of progression of disease activity, were considered. Results: Our study showed that both PUVA and NB-UVB are effective in the treatment of vitiligo. Both treatment methods showed a good repigmentation especially over the face, with a poor response on the feet and hands. The overall grade of repigmentation was better with NB-UVB than PUVA. The adverse effects were marginally more with PUVA therapy. Conclusion: Thus, it was proven in our study that both PUVA and NB-UVB are effective for the treatment of vitiligo. However, NB-UVB has proved to have a distinct edge over PUVA in terms of better efficacy and lesser adverse effects.
Keywords: Narrow-band ultraviolet B, psoralen with ultraviolet A, repigmentation, vitiligo
|How to cite this article:|
Gaikwad AV, Bharatia PR. Study of efficacy of phototherapy (psoralen with ultraviolet A and narrow-band ultraviolet B) in vitiligo. Pigment Int 2016;3:11-6
| Introduction|| |
Vitiligo is an acquired idiopathic skin disorder, characterized by well-circumscribed, depigmented macules with an immense psychosocial impact. It is more significant in the dark-skinned population, with a major impact on the quality of life of patients.,, It is a progressive disorder in which the melanocytes in the affected skin are selectively destroyed.
Mode of therapy is based on decreasing disease activity and inducing pigmentation. Multiple medical and surgical therapies are available, but none is a definitive cure. Ultraviolet (UV) light-based therapy has been a mainstay of therapy for vitiligo for many decades. The earliest form was psoralen and UVA (PUVA) photochemotherapy. Currently, the most commonly used form is narrow-band UVB (NB-UVB) and for limited areas, targeted phototherapy (excimer laser or excimer lamp). Best repigmentation rates do not reach figures beyond 70%, with acral regions and lesions with leucotrichia being most difficult to repigment.
There are few studies on the efficacy of phototherapy from the Western region of India. The population in this region is ethnically different from that in other parts of the country. With this background, we evaluated the efficacy of phototherapy (PUVA and NB-UVB) in patients with vitiligo and compared their response to the same (PUVA vs. NB-UVB). We also wanted to find out if our study endorses the results of similar studies conducted by authors in other parts of the country. We studied the efficacy of phototherapy (PUVA and NB-UVB) in patients with vitiligo and compared the response to phototherapy (PUVA vs. NB-UVB) in vitiligo.
| Methods|| |
This was a prospective study of sixty patients attending the dermatology outpatient department of our hospital. The study was conducted over a period of 2 years. Ours is a well-known tertiary referral center for all medical facilities including dermatology. This study was conducted after obtaining an approval from the “Ethics Committee” at our hospital.
Patients attending the dermatology outpatient department of our hospital were recruited. The diagnosis of vitiligo was confirmed clinically and by a chalky white appearance on Wood's lamp examination. Consent was taken after explaining the benefits and due risks of therapy.
Sample size and sample technique
A total of 60 patients were enrolled into two different groups PUVA and NB-UVB. The patients were randomly divided into two treatment groups (30 PUVA + 30 NB-UVB) by a computerized random table method and were treated accordingly in a full body phototherapy unit for 1 year. These were the patients satisfying the inclusion and exclusion criteria and willing to participate in the study including the follow-up. An informed consent was taken from every patient. The routine ophthalmological examination was done. The approximate percentage of body surface area involved was calculated using the “Rule of Nine.”
- Previously untreated patients
- Old cases not taking any treatment for last 6 months
- Patients of age >12 years for PUVA.
- Patients on treatment within the last 6 months
- Patients with a history of photosensitivity, photosensitive disorders, or history of drug intake known to cause photosensitive reactions
- Pregnant women
- Known cases of HIV/AIDS
- Children of age <12 years for PUVA.
A prospective comparative study was conducted. The required data about the patients was collected according to the case proforma after thorough history taking, clinical examination, and laboratory investigations when required. Pre- and post-treatment vitiligo disease activity (VIDA) scoring was done and photographs taken. The patients were then assigned to the PUVA or NB-UVB group randomly. The patients in both the groups were studied during follow-up visits every month and in between in case of any adverse effects.
Those patients who failed to show any repigmentation even after 3 months of regular and adequate treatment were considered as nonresponders, and further treatment was stopped. In the case of responsive patients, the treatment was continued for a maximum period of 1-year.
Therapy was given thrice a week for PUVA and twice a week for NB-UVB on nonconsecutive days. Minimal erythema dose was not calculated as all the patients were of skin type IV and V, a standard initial dose of 1 J/cm 2 for PUVA and 300 mJ/cm 2 for NB-UVB was started. Patients on PUVA therapy took trimethylpsoralen tablets in a dose of 0.6 mg/kg body weight 2 h before phototherapy. Patients were not started on any other modality of treatment except in cases of progressive vitiligo where short course oral steroid minipulse therapy (prednisolone 20 mg twice a week) was given for 4 weeks.
The irradiation dose was increased by 20% for NB-UVB and by 0.5 J/cm 2 for PUVA at each subsequent visit. The optimal constant dose was achieved when minimal pink erythema occurred in the lesions. If the erythema was asymptomatic, the same dose was held. After each treatment session patients were advised to apply sunscreen on exposed areas and to avoid excessive sun exposure.
Two primary parameters, repigmentation and arrest of progression of disease activity, were considered to evaluate the response to treatment.
Patients were followed up for 1 year at monthly intervals. At each visit, repigmentation was assessed, and grades in each topographical area are as follows:
- Grade 0 = 0
- Grade 1= <25 %
- Grade 2 = 25–50%
- Grade 3 = 50–75%
- Grade 4= >75%.
Color of repigmentation was graded as:
- Good match: Same color as surrounding normal skin
- Somewhat darker
The pattern of repigmentation was assessed as perifollicular, marginal, diffuse, and combined.
The disease activity was graded by means of “vitiligo disease activity score” before and after 12 months of treatment. This is a scoring system based on the patient's opinion of the present disease activity within the time periods indicated in [Table 1].
The term “active” is defined as the expansion of existing lesions or the appearance of new lesions. “Stable” refers to the condition when these symptoms are not present.
The final outcome was recorded as a success if patients achieved more than 50% repigmentation along with stabilization of disease.
Data analysis was done by using Statistical package for social sciences version 17.0 Manufactured by SPSS inc. Released 2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS inc. We have used the two independent sample t-test to compare the demographic parameters (age, gender, duration of disease, age of onset, and body surface area%). Fisher's exact test was used to find out an association between the presence of family history of disease in Group I and II. Mann–Whitney U-test was used to test the significance of the difference between the grade of repigmentation, color and pattern of repigmentation, and VIDA scores before and after treatment in Group I and II. Wilcoxon sign-rank test was used in each group individually to test the significance of the difference in VIDA scores before and after treatment. Chi-square t-test was used to find an association between the occurrence of adverse effects with treatment given in Group I and II.
| Results|| |
In the present series, sixty patients diagnosed clinically as vitiligo were included to study the relative efficacy of PUVA and NB-UVB phototherapy after 1 year of treatment. The youngest patient was 15 years of age and the oldest 65 years. Patients were arranged into two treatment groups (PUVA and NB-UVB) containing 30 patients each. Treatment was discontinued in 3 patients of PUVA and 1 patient of NB-UVB groups due to no response even after 3 months of adequate treatment. The results were compared with work done on this topic in India.
As mentioned in [Table 2], there was no statistically significant difference between the demographic data of Group I and II. Consistent with literature,,, the number of female patients presenting to us were more than males. This difference may be related to increased cosmetic awareness and now also due to the awareness amongst masses of the availability of newer treatment modalities. During patient selection, a balance was maintained in the various morphological types of vitiligo in both groups.
In the PUVA group, 5 (16.66%) patients and 9 (30%) patients in the NB-UVB group achieved >75% repigmentation. 7 (23.33%) patients in the PUVA group and 10 (33.33%) patients in the NB-UVB group achieved 50–75% repigmentation. 8 (26.66%) patients in the PUVA group and 7 (23.33%) patients in the NB-UVB group achieved 25–50% repigmentation. 6 (20%) patients in the PUVA group and 3 (9.09%) patients in the NB-UVB group achieved 0–25% repigmentation. Overall, in this study, more than 50% repigmentation was achieved in 12 (40%) patients in the PUVA group and 19 (63.33%) patients in the NB-UVB group. In addition, the median grade of repigmentation was grade 2 in the PUVA group and grade 3 in the NB-UVB group. By using Mann–Whitney U-test, P = 0.032, therefore there is a statistically significant difference between a median grade of repigmentation in the two groups with NB-UVB offering a better therapeutic response.
In the PUVA group, 22 (73.33%) patients and in the NB-UVB group 24 (80%) had a VIDA score of 1 and higher before therapy. The disease stabilized (score 0) in 26 (86.66%) in the PUVA group and 28 (93.33%) in the NB-UVB group after therapy. The median VIDA score in both groups before therapy was 1 (P = 0.884) and it reduced to 0 (P = 0.349) in both groups after therapy. By using Wilcoxon sign-rank test, there was a statistically significant improvement in the VIDA score in each of the two groups individually, however, by using the Mann–Whitney U-test, there is no statistically significant difference after comparing the median VIDA scores in Group I and II at before treatment and after treatment. Better disease stability was achieved NB-UVB than with PUVA.
There was good color match with the adjacent area in 13 (43.33%) patients in the PUVA group and 21 (70%) patients in the NB-UVB group. The color of repigmented area was darker in 13 (43.33%) patients in the PUVA group and 7 (23.33%) patients in the NB-UVB group. The color of repigmented area was lighter in 1 (3.33%) patient in the NB-UVB group who showed a diffuse pattern of repigmentation. Although, clinically, the color match was better in the NB-UVB group than the PUVA group, this was not proven statistically (Fisher's exact test, [P = 0.096]).
After therapy, 23 (76.66%) patients in the PUVA group and 22 (73.33%) patients in the NB-UVB group had predominantly perifollicular repigmentation. It was combined type (both perifollicular and marginal) in 3 (10%) patients in the PUVA group and 5 (16.66%) patients in the NB-UVB group. In the NB-UVB group, 1 (3.33%) showed predominantly marginal repigmentation and 1 (3.33%) showed predominantly diffuse repigmentation. Overall perifollicular was the most common pattern of repigmentation observed in both groups. Moreover, by using Fisher's exact test (P = 0.143) there was no association between pattern of repigmentation and the treatment given. Thus, both PUVA and NB-UVB groups showed predominantly perifollicular repigmentation. Marginal and diffuse repigmentation was seen only in the NB-UVB group.
Out of 20 patients in the PUVA group with vitiliginous macules on the face (excluding patients with lip involvement), 14 (70%) achieved repigmentation >75%. Similarly, out of 22 patients in the NB-UVB group, 17 (77.27%) achieved repigmentation >75%. The next best response was seen on the arms, with 12 (40%) patients in PUVA and 11 (36%) patients in NB-UVB group achieving repigmentation >75%. The areas showing the worst response were feet and hands followed by elbows. No response was seen on the feet in 15 (50%) patients in PUVA and 18 (60%) patients in NB-UVB group. Similarly on the hands, 14 (46%) patients in PUVA and 13 (43%) patients in NB-UVB group showed no response. In conclusion, at all sites repigmentation was better in the NB-UVB group than PUVA group, with the best response on the face and the worst on feet and hands.
Ensuring adequate patient education regarding rigorous following of precautionary measures, both forms of treatment were reasonably well-tolerated. The side effects noted were mild and transient in the form of erythema, dryness, pruritus; and nausea in patients on PUVA therapy. The most common side effect in both groups was erythema (8 [26.66%] in PUVA and 5 [16.66%] in NB-UVB group). All the cutaneous side effects were temporary and reversible and did not lead to discontinuation of treatment in any of the patients. None of the patients developed blisters. The side effects were fewer in the NB-UVB group 6 (20%) than the PUVA group 16 (53.33%) this difference being statistically significant (Chi-square t-test [P value 0.015]).
In the PUVA group, 12 (40%) patients achieved repigmentation >50% along with stabilization of previously active lesions after 1 year of treatment. In the NB-UVB group 19 (63.33%) patients achieved the same. Overall, NB-UVB resulted in higher repigmentation rates than PUVA.
| Discussion|| |
It was proven that in both treatment groups, there was a statistically significant difference in both the groups in terms of grade of repigmentation and occurrence of adverse effects. NB-UVB showed better results and fewer adverse effects than PUVA. It was also proven that there is no significant difference in the color and pattern of repigmentation in both the groups. Although not statistically proven, the color match was observed to be better with NB-UVB than PUVA. The most common pattern of repigmentation observed in both groups was perifollicular followed by combined type (both perifollicular and marginal). The improvement in VIDA scores after treatment was proven to be statistically significant in each of the two groups individually. However, there was no statistically significant difference in the posttreatment VIDA score in the PUVA group compared to the NB-UVB group. This difference could be due to the relatively small sample size which may become statistically significant if the sample size were increased. In a similar study by Bhatnagar et al., stabilization of disease was better with NB-UVB than PUVA although not proven to be statistically significant.
The best response was observed on the face followed by arms. The areas showing poor response were feet and hands followed by elbows. The adverse effect common to both groups was erythema. It was observed more frequently in the PUVA group than the NB-UVB group. This difference was also proven to be statistically significant. Few patients in both groups also had pruritus. A single patient in the PUVA group had nausea. None of these adverse effects were severe enough to cause discontinuation of therapy.
In our prospective study, we compared the efficacy of PUVA therapy with NB-UVB therapy in demographically matched vitiligo patient populations which, showed that both PUVA and NB-UVB are effective in the treatment of vitiligo. However, the overall grade of repigmentation was better with NB-UVB than PUVA [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5]. The adverse effects were marginally more with PUVA therapy. The results of our study echo with the results of studies by Parsad et al., Bhatnagar et al., Sapam et al., and Yones et al. NB-UVB has proved to have a distinct edge over PUVA in terms of better efficacy and lesser adverse effects.
|Figure 1: (a) Before treatment with narrow-band ultraviolet B. (b) After 5 months of narrow-band ultraviolet B therapy|
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|Figure 2: (a) Before treatment with narrow-band ultraviolet B. (b) After 3 months of narrow-band ultraviolet B therapy|
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|Figure 3: (a) Before treatment with narrow-band ultraviolet B. (b) After 2 months of narrow-band ultraviolet B therapy|
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|Figure 4: (a) Before treatment with psoralen with ultraviolet A. (b) After 6 months of psoralen with ultraviolet A therapy|
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|Figure 5: (a) Before treatment with psoralen with ultraviolet A. (b) After 4 months of psoralen with ultraviolet A therapy|
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| Limitations and Recommendations|| |
As the study was limited to the same institute, a multicenter and multivariate trial should be done. A larger sample size would have given a more elaborate and accurate result regarding efficacy and side effects. Similar studies can be conducted in childhood vitiligo and segmental vitiligo. Efficacy of NB-UVB can be evaluated in pregnant women with vitiligo and in immunosuppressed individuals with vitiligo. More studies are required to study the efficacy of phototherapy in patients with vitiligo associated with hormonal imbalance and autoimmune diseases. Studies can be conducted to assess the efficacy of phototherapy with other systemic modalities for the holistic treatment of vitiligo.
| Conclusion|| |
Both PUVA and NBUVB are effective for the treatment of vitiligo. However, NBUVB has a distinct edge over PUVA in terms of better efficacy and lesser adverse effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kumar R, Parsad D. Melanocytorrhagy and apoptosis in vitiligo: Connecting jigsaw pieces. Indian J Dermatol Venereol Leprol 2012;78:19-23.
Parsad D. Vitiligo emerging paradigms. Indian J Dermatol Venereol Leprol 2012;1:17-18.
Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes 2003;1:58.
Parsad D, Pandhi R, Dogra S, Kumar B. Clinical study of repigmentation patterns with different treatment modalities and their correlation with speed and stability of repigmentation in 352 vitiliginous patches. J Am Acad Dermatol 2004;50:63-7.
Behl PN, Aggarwal A, Srivastava G. Vitiligo. In: Behl PN, Srivastava G, editors. Practice of Dermatology. 9th
ed. New Delhi: CBS Publishers; 2003. p. 238-41.
Handa S, Dogra S. Epidemiology of childhood vitiligo: A study of 625 patients from north India. Pediatr Dermatol 2003;20:207-10.
Cho S, Kang HC, Hahm JH. Characteristics of vitiligo in Korean children. Pediatr Dermatol 2000;17:189-93.
Bhatnagar A, Kanwar AJ, Parsad D, De D. Psoralen and ultraviolet A and narrow-band ultraviolet B in inducing stability in vitiligo, assessed by vitiligo disease activity score: An open prospective comparative study. J Eur Acad Dermatol Venereol 2007;21:1381-5.
Parsad D, Kanwar AJ, Kumar B. Psoralen-ultraviolet A vs. narrow-band ultraviolet B phototherapy for the treatment of vitiligo. J Eur Acad Dermatol Venereol 2006;20:175-7.
Sapam R, Agrawal S, Dhali TK. Systemic PUVA vs. narrowband UVB in the treatment of vitiligo: A randomized controlled study. Int J Dermatol 2012;51:1107-15.
Yones SS, Palmer RA, Garibaldinos TM, Hawk JL. Randomized double-blind trial of treatment of vitiligo: Efficacy of psoralen-UV-A therapy vs. Narrowband-UV-B therapy. Arch Dermatol 2007;143:578-84.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]