A Retrospective Study of 3,000 Indian Patients with Vitiligo Treated with Phototherapy or Topical Monotherapy

J Clin Aesthet Dermatol. 2021;14(2):46–49.

by Jagdish Sakhiya, MD; Dhruv Sakhiya, MBBS Student; Neha Virmani, MBBS, MD, DNB; Trusha Gajjar, DVD; Jitesh Kaklotar, DDV; Ravi Khambhati, MBBS, DVD; Feral Daruwala, MPharm; and Nimish Dudhatra, MSC CR

Drs. J. Sakhiya, Virmani, Gajjar, Kaklotar, Khambhati and Mr. Daruwala and Mr. Dudhatra are with Sakhiya Skin Clinic Pvt. Ltd. in Surat, Gujarat, India. Dr. D. Sakhiya is with B. J. Medical College in Ahmedabad, Gujarat, India.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

ABSTRACT: Background: Vitiligo-affected individuals, especially patients with darker skin tones, can suffer from negative psychosocial impacts due to unpredictable development of the condition and perceived cosmetic concerns. However, given that spontaneous repigmentation can be gained in vitiligo, many patients ask for treatment due to these cosmetic concerns. In the literature, only a few studies have been documented focusing on the outcome of various treatment modalities for vitiligo.

Objective: This article highlights the retrospective response of various treatment modalities in Indian patients with vitiligo.

Methods: A retrospective chart review was performed from July 2017 to August 2018 at our private dermatology clinic. A total of 3,000 patients were enrolled in this observational study. Patient characteristics and details of phototherapy (psoralen and ultraviolet A, narrow-band ultraviolet B, excimer laser) were noted as per a predefined format. The clinical response was evaluated as a marked response, defined as repigmentation in more than 75% of the initial lesional area.

Results: In the present study, 1,996 patients received phototherapy and 1,004 patients were treated with topical monotherapy. Patients treated with phototherapy only and those treated with a combination of phototherapy and topical agents showed significantly higher clinical response rates relative to patients treated with topical monotherapy only (marked response rate: 47.8% vs. 8.7%; P<0.001 and 23.4% vs. 8.7%; P<0.001). Disease subtype predominately affected the treatment response.

Conclusion: In Indian patients with vitiligo, phototherapy appears to be an effective treatment option for both focal and vitiligo vulgaris. Due to its reliability and minimal side effects, it can be considered a preferable treatment modality for vitiligo.

KEYWORDS: Excimer laser, focal vitiligo, narrowband UVB ultraviolet A, psoralen, topical therapy, vitiligo vulgaris

Vitiligo is a pigmentary disorder of the skin characterized by circumscribed depigmented macules and patches. The progressive and selective destruction of melanocytes resulting in partial to complete loss of pigmentation is the main mechanism involved in its pathogenesis. It affects 0.5 to 2 percent of the entire population worldwide and usually occurs in childhood or young adulthood. Many studies have reported an onset of disease before the age of 20 years in around half of patients. Although vitiligo may be more evident in patients with darker skin, the condition has no racial or ethnic predilection.¹ 

Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis that may occur due to genetic as well as nongenetic factors. Even though several theories—including autoimmune mechanisms, cytotoxic mechanisms, intrinsic melanocyte defects, oxidant–antioxidant mechanisms, and neural mechanisms—have been proposed for its pathogenesis, the precise cause remains unknown.² 

The advent of various treatment modalities in vitiligo—including phototherapy (psoralen and ultraviolet A [PUVA], narrowband ultraviolet B [NBUVB], and 308-nm excimer laser), topical therapy (topical corticosteroids, topical vitamin D3 analogs, and topical calcineurin inhibitors), and surgical therapy (suction blister grafts, split-thickness grafts, and miniature grafts)—has dramatically changed the dilemma regarding the selection of the proper treatment approach. As per recently published studies, topical corticosteroids are the preferred agents for management of localized vitiligo and phototherapy is a good alternative for generalized vitiligo.^3,4 However, inconsistencies in study designs and outcome measures are major drawbacks in these studies. To date, no definitive treatment algorithm has yet been established for this condition. Further, variations in patient’s characteristics, including skin color, age, disease duration, and the extent and type of vitiligo may lead to a discrepancy in treatment response. It is, therefore, essential to gather sufficient evidence to establish a standardized treatment protocol.⁵ This study was carried out with the aim to assess the response to various types of treatment modalities in 3,000 Indian vitiligo patients.

Methods

This study was a retrospective observational study carried out from July 2017 to August 2018 at our private dermatology clinic. The study was conducted in accordance with the 1975 Declaration of Helsinki. Written informed consent was obtained before enrollment. In total, 3,000 patients with signs of vitiligo were enrolled in the study, regardless of sex or age. 

Study participant characteristics. The patients’ characteristics (age, age at onset, duration, sex, family history, comorbidities, disease localization, disease subtype, halo nevi, Koebner phenomenon, leucotrichia) and the treatment course were recorded. Apart from these, laboratory results, including thyroid function tests (thyroid-stimulating hormone, free thyroxine, antithyroglobulin antibodies, and antithyroid peroxidase antibodies) and the presence of other autoantibodies, were also assessed. 

Phototherapy. When phototherapy (PUVA, NBUVB, excimer laser) was used, the modality, duration of treatment, frequency, initial dose, total amount of irradiation, adverse events (AEs), and concomitant use of topical therapy (e.g., corticosteroids, calcineurin inhibitors, or vitamin D3 analogs) were recorded. The mean initial doses were 0.14 J/cm² for PUVA, 0.28 J/cm² for NBUVB, and 0.14 J/cm² for excimer laser therapy. The optimal maintenance dose was set below the minimal erythema dose. Topical/oral psoralen was applied before ultraviolet A exposure. Topical treatment over six months either as the monotherapy or together with phototherapy was taken into consideration.

Clinical outcomes. Clinical outcomes were evaluated using the following repigmentation grading: no response, mild response (<25% repigmentation), moderate response (25%–50% repigmentation), good response (50%–75% repigmentation), and marked response (>75% repigmentation).⁶

Statistical analysis. Data were analyzed using the Statistical Package for the Social Sciences version 21 (IBM Corporation, Armonk, New York) at the significance level of 0.05; quantitative data were expressed as mean ± standard deviation values and categorical data were presented as frequency (percentage) values. The chi-squared test (in the case of sample size >1,000) and Fisher’s exact probability test (in the case of sample size <1,000) were used for the analysis of frequencies. 

Results 

During the study period, a total of 3,000 patients were diagnosed with vitiligo at our center; their clinical characteristics are detailed in Table 1. Of these, 1,755 (58.5%) were male and, 1,245 (41.5%) were female, with a male-to-female ratio of 1.4:1. The average age of onset was 35.3±21.0 years. Mean duration of disease was 5.8±8.2 years. A family history of vitiligo (n=182; 6.1%) was less common. The majority of patients had nonsegmental vitiligo (n=2,290; 76.3%), with acrofacial vitiligo (n=912; 30.4%) being the most common subtype, followed by vitiligo vulgaris (23.7%). On the other hand, segmental vitiligo (n=631; 21.0%) was a less common form in our study. The most common lesion site was the face (54.3%), followed by the chest and abdomen (31.5%), hands (7.5%), and neck (6.7%). Topical corticosteroids were used by 40.2 percent of the patients; topical vitamin D3 derivatives (26.3%), topical calcineurin inhibitors (15.5%), and topical psoralen (18%) were also used, respectively. Atopic dermatitis was the most common comorbidity, affecting 5.8 percent of cases, followed by hypothyroidism (2.7%), hyperthyroidism (0.7%), and alopecia areata (0.5%). Halo nevi, koebnerization, and leucotrichia were rare and occurred in less than five percent of our study population.

Treatment responses are detailed in Table 2. Among 3,000 patients, 1,996 were treated with phototherapy and the remaining 1,004 patients were treated with topical monotherapy. The efficacy of phototherapy was superior to that of topical monotherapy, with marked response rates of 47.8 and 8.7 percent, respectively (P<0.001). There were statistically significant differences in the therapeutic response to phototherapy based on disease subtype (P<0.001); recorded marked response rates were 9.8 percent (segmental), 4.8 percent (acrofacial), 19.1 percent (focal), and 18.2 percent (vulgaris). Among the 1,996 patients who received phototherapy, 367, 978, and 651 patients were treated with PUVA, NBUVB, and excimer laser therapy, respectively. The mean numbers of irradiations performed using each modality were 23.1, 25, and 38.7, respectively. Of those treated with PUVA, 33.8 percent showed marked responses, while 18.8 percent of those treated with NBUVB and 10 percent of those treated with excimer laser therapy showed marked improvement. Consequently, the marked response rate to PUVA (42.9%) was significantly higher relative to that of non-PUVA phototherapy (15.3%; P<0.001). 

Some previously reported studies have hypothesized that the concomitant use of topical medicine with phototherapy may improve the therapeutic outcome.^6,7 For that reason, we kept one question in mind: is the administration of topical therapy, along with phototherapy, capable of improving therapeutic outcomes in this study population? Therefore, among the 1,996 patients treated with phototherapy, 1,083 patients received topical therapies as well, while the remaining 913 patients received just phototherapy. Concomitant use of phototherapy and topical ointment showed significantly higher treatment efficacy relative to topical monotherapy and also appeared to be more effective than phototherapy alone (marked response: 23.4% vs. 8.7%; P<0.001 and 23.4% vs. 7.3%; P<0.001).

During the study period, only mild adverse reactions were observed and no patients discontinued treatment. When higher joules of excimer light were applied, blistering occurred in about 10.1 percent of patients, whereas, skin irritations and itching occurred in approximately 15.3 percent of patients receiving PUVA. No adverse reactions were observed in the NBUVB treatment group.

Discussion

Yoshida et al⁸ conducted a similar type of study involving 231 Japanese patients, where the mean age of onset was 33.1±23.0 years, which was slightly higher than that in our study. In their study, the incidence of vitiligo was highly predicted in men (52.38%), which correlated with our finding of a male predominance (58.5%). Also, halo nevi, Koebnerization, and leucotrichia were rarely reported in this study and these findings are supported by Kong et al.⁹ Recently, an autoimmune aetiology has become most widely accepted¹⁰ and, possibly, genetic factors may play a crucial role in the pathogenesis of this condition. Vitiligo has been reported to be associated with a variety of autoimmune disorders such as adrenal insufficiency, pernicious anaemia, diabetes mellitus, and thyroid disease.^11,12 Hence, to rule out proper etiology, adequate knowledge regarding family history, antinuclear antibody titer, and thyroid function test results is of paramount importance. Interestingly, 76.3 percent (n=2,290) of our patients presented with nonsegmental vitiligo. Acrofacial (30.4%) was the most common subtype of nonsegmental vitiligo. Then, focal and vulgaris were ranked. This differed from findings in the existing literature on vitiligo, in which vitiligo vulgaris (42.9%) was more prevalent, followed by focal vitiligo (29.6%).The most involved location in the current study was the face, followed by the chest/abdomen, hands, and neck. Similar findings were obtained by Yoshida et al.⁸ In our study, the prevalence of vitiligo was higher (5.8%) in patients with atopic dermatitis, which concurs with the existing literature.⁸

Over the past few decades, a common credo has been embraced among the general population that vitiligo is a condition that cannot be cured. This credo is perpetuated, in part, by the slow response to therapy shown by many patients. Another reason may be dermatologists’ reluctance to treat the disease due to a low estimated or perceived efficacy of available nonsurgical repigmenting therapies.¹³ In the new era, this historical trend has changed due to the development of various phototherapies that can significantly improve the clinical picture in many cases, yet, a complete cure remains out of reach. Additionally, the therapeutic effects of existing treatments are inconsistent and individualized among patients, who also occasionally fail to maintain their initial response to phototherapy.⁸ However, in light of the psychologically destructive nature of the disease, improvements in treatment outcomes are mainly in demand. 

 As envisioned, phototherapy—particularly the combination of phototherapy and topical therapy—was considerably more effective than topical monotherapy. Recently proposed guidelines have stated that phototherapy is a treatment of choice when traditional therapy is futile.⁹

In the present study, the safety evaluation showed blistering, skin irritations, and itching in patients treated with phototherapy, which resolved spontaneously. As yet, skin cancer did not occur in any of the patients treated with phototherapy during the entire study period. Nevertheless, unlike NBUVB,¹⁴ PUVA carries a somewhat increased risk of both nonmelanoma skin cancer and melanoma.¹⁵ In agreement with Felsten, premature photoaging of the skin is also a predicament associated with extended use of phototherapy.¹⁶ It is therefore essential to provide a detailed description of these potential long-term adverse effects to patients and to collect written informed consent before pursuing the use of phototherapy. 

NBUVB has been proved to be superior to PUVA in terms of more cosmetically acceptable repigmentation, especially for unstable extensive vitiligo.^17–22 Therefore, NBUVB would be the recommended phototherapy for vitiligo, although, in some cases, PUVA can also be suggested, expressly if there is a lack of response to NBUVB. According to Nicolaidou et al,²³ monochromatic excimer light of 308 nm in wavelength has shown remarkable improvement relative to NBUVB in the treatment of the vitiligo. In our study, however, excimer laser therapy produced unimpressive results. The reason behind this may be the difference in laser response according to site treated. Nicolaidou et al²³ postulated that, when treated with excimer laser, a statistically significantly better response was observed in the ultraviolet-sensitive areas (face, neck, back, breast, and arm) as compared with ultraviolet-resistant areas (knees, elbows, wrists, hands, ankles, and feet).

In our study, the clinical efficacy of PUVA was better than that of both NBUVB and excimer laser therapy. The reason behind this is that a relatively small number of patients were treated with PUVA as compared with those treated with NBUVB or excimer laser as PUVA and NBUVB are presently widely used modalities in our private clinic. Because of the major difference in the number of patients enrolled in the PUVA, NBUVB, and excimer study groups, the results in favor of any one therapy may become a matter of debate. Moreover, PUVA may be more successful for a specific population of patients with vitiligo and further research is therefore required. Findings from the current study revealed that clinical subtypes of vitiligo markedly affect the response to phototherapy. Do et al.²⁴ proposed that, for segmental vitiligo, the high cumulative ultraviolet energy of the excimer laser achieves better responses. Similarly, because excimer laser can only be applied to a limited, small, depigmented lesion, phototherapy should be considered for both focal and generalized depigmentation. Many reported studies have found a better response rate in patients with generalized vitiligo by using the NBUVB treatment modality.^25–27 

 Limitations. The present study is limited by its retrospective nature. Although the sample size was adequate for the study, the lack of a control group can also cause bias. Moreover, the lack of uniformity in outcomes evaluations was unavoidable because cases were consulted by different dermatologists of the clinic.

Conclusion

In summary, phototherapy, particularly in Indians, had a more beneficial therapeutic effect on both focal and vitiligo vulgaris, although it was favorable to some degree in all subtypes of vitiligo. It is generally safe and well-tolerated, with slight, temporary side effects, although questions about long-term side effects—in particular, photocarcinogenesis—necessitate further evaluation.

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