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 Table of Contents  
Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 56-59

Current best evidence from pigmentary dermatology

Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Web Publication17-Jun-2016

Correspondence Address:
Dr. Devinder Mohan Thappa
Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2349-5847.184246

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How to cite this article:
Chiramel MJ, Malathi M, Thappa DM. Current best evidence from pigmentary dermatology. Pigment Int 2016;3:56-9

How to cite this URL:
Chiramel MJ, Malathi M, Thappa DM. Current best evidence from pigmentary dermatology. Pigment Int [serial online] 2016 [cited 2022 Aug 11];3:56-9. Available from: https://www.pigmentinternational.com/text.asp?2016/3/1/56/184246

Whitton M, Pinart M, Batchelor JM, Leonardi-Bee J, Gonzalez U, Jiyad Z, et al. Evidence-based management of vitiligo: Summary of a Cochrane systematic review. Br J Dermatol 2016;174:962-9.

Vitiligo affects around 1% of the world's population. Despite it being relatively common, there is still no effective treatment. The objective of this study was to update the Cochrane systematic review of randomized clinical trials (RCTs) to evaluate the efficacy of treatments for vitiligo. We carried out searches of a range of databases to October 2013 for RCTs of interventions for vitiligo regardless of language or publication status. At least two reviewers independently assessed study eligibility and methodological quality and extracted data using data extraction forms approved by the Cochrane skin group. Our primary outcomes of interest were quality of life (QoL), >75% repigmentation, and adverse effects. We retrieved 96 studies, of which 39 were new studies, with an overall total of 4512 participants. Repigmentation was assessed in all studies although only five reported on all three of our primary outcomes. Regarding our two secondary outcomes, six studies measured cessation of spread, but none assessed long-term permanence of repigmentation at 2 years' follow-up. Most of the studies evaluated combination treatments, which generally showed better repigmentation than monotherapies. Of the new studies, seven were surgical interventions. The majority of the studies had fewer than 50 participants. The quality of the studies was poor to moderate at best. Very few studies specifically included children or participants with segmental vitiligo. Five years after the last update of this review, there are still important variations in study design and outcome measures in clinical trials for vitiligo, limiting the evidence for the efficacy of different therapeutic options. The best evidence from individual trials showed short-term benefit from topical corticosteroids and various forms of ultraviolet (UV) radiation combined with topical preparations. Long-term follow-up and patient-rated outcomes should be incorporated into study design, and more studies should assess psychological interventions.

Comments: Considerable progress has been made in the understanding of the pathogenesis of vitiligo, and the disease is now clearly classified as autoimmune with a probable genetic background associated with metabolic, oxidative stress and cell detachment abnormalities. Because of the complex interactions between different factors in vitiligo, a variety of different treatments are used although none of them is fully satisfactory. Possible treatment options include topical corticosteroids, calcineurin inhibitors, Vitamin D derivatives, phototherapy (UVA, narrowband UVB [NB-UVB], photochemotherapy with psoralen plus UVA [PUVA], psoralen with sunlight), surgical techniques, and combinations of topical therapies and light treatment. In this review, there was not enough information to analyze the effect on QoL. NB-UVB was better than PUVA in achieving 75% repigmentation, but this difference was not statistically significant. The adverse effects noticed were similar to what is described in literature except an increased incidence of nausea with NB-UVB than PUVA which could not be explained. Cessation of activity with treatment versus placebo was seen only in one study with Ginko biloba. There were no studies that assessed long-term repigmentation. The dearth of high-quality studies with sizable sample size was a limiting factor. The authors conclude that although there are many treatment modalities for vitiligo, there is none specifically licensed and none fully effective.

Bae JM, Hong BY, Lee JH, Lee JH, Kim GM. The efficacy of 308-nm excimer laser/light (EL) and topical agent combination therapy versus EL monotherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials (RCTs). J Am Acad Dermatol 2016;74:907-15.

Combination therapies of excimer laser/light (EL) and various topical agents are widely used in the treatment of vitiligo. This study thought to compare the efficacy of EL and topical agent combination therapy versus EL monotherapy for vitiligo. Manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, and Cochrane library (from inception through December 15, 2014) were conducted to identify randomized controlled trials that assessed the efficacy of EL alone or in combination with topical agents for vitiligo. The primary outcome was treatment success (≥75% repigmentation), and the secondary outcome was treatment failure (<25% repigmentation); meta-analyses were performed when possible. They analyzed 8 randomized controlled trials comprising a total of 425 patches/patients. The combination of EL and topical calcineurin inhibitors (four studies: Relative risk 1.93, 95% confidence interval [CI] 1.28–2.91; number needed to treat 4.5, 95% CI 2.9–10) was superior to EL monotherapy for vitiligo. There was insufficient evidence to support beneficial effects of topical Vitamin D3 analogs (three studies) and corticosteroids (one study). These findings are based on small numbers of randomized controlled trials and heterogeneities among included studies are another limitation. It was concluded that topical calcineurin inhibitors in conjunction with EL are more effective compared with EL monotherapy.

Comments: Vitiligo is a challenging dermatological disorder in which many treatment modalities have been tried. Phototherapy is one of the mainstay of treatment in vitiligo. EL was recently introduced to the treatment of vitiligo and has demonstrated a superior efficacy and faster response than conventional phototherapies such as PUVA and NB-UVB. It is a common practice to combine topical agents such as topical steroids, calcineurin inhibitors, and Vitamin D3 analogs along with EL to obtain a better clinical response. This meta-analysis of randomized controlled trials addresses this issue and collects evidence for this rationale. It is shown that there is the highest level of evidence for combining calcineurin inhibitors with EL. Although there are concerns about the potential carcinogenicity of combining immunosuppressants with phototherapy, tacrolimus has been shown to be protective against UV-induced DNA damage and erythema by inhibiting early phase inflammatory events in other studies. Further good quality studies are needed, especially regarding use of other topical agents such as corticosteroids and Vitamin D3 analogs for complete assessment of combination therapy.

Komen L, van der Kraaij GE, van der Veen JP, de Rie MA, Wolkerstorfer A. The validity, reliability and acceptability of the SAVASI; a new self-assessment score in vitiligo. J Eur Acad Dermatol Venereol 2015;29:2145-51.

Vitiligo is a common depigmenting skin disorder that can influence a patient's quality of life (QoL). Although patient-orientated medicine is an emerging concept, a self-assessment tool to assess the degree of depigmentation in vitiligo is not yet available. Therefore, authors developed the Self-Assessed Vitiligo Area and Severity Index (SAVASI), a self-assessment tool that uses the same basic principles as the VASI. The objective of the study was to assess the validity, reliability, and acceptability of the SAVASI. To assess the validity of the SAVASI, they compared the scores assessed by the patient with the scores of the VASI assessed by the physician. To assess the intra-rater reliability, the correlation between the baseline SAVASI and the SAVASI after 2 weeks was calculated. To assess the acceptability, patients indicated the time needed to complete the SAVASI and the patient assessed the difficulty of the questionnaire on a five-point scale. The Skindex-29 was used to determine the QoL. The overestimation of the SAVASI compared to the VASI was calculated by subtracting the VASI scores off from the SAVASI scores. A high correlation between the VASI and the SAVASI (intraclass correlation coefficient [ICC] 0.97, 95% confidence interval [CI]: 0.95–0.98) was found in 60 patients. The intra-rater reliability of the SAVASI (ICC 0.75, 95% CI 0.54–0.87) was adequate in 31 patients. Fifty (83%) patients completed the questionnaire within 10 min and only 5 (8%) patients considered the SAVASI hard. They found no correlation between overestimation of the SAVASI score and the Skindex-29 score. The SAVASI is a valid, reliable, and acceptable self-assessment tool to measure the degree of depigmentation in vitiligo. With the SAVASI, the degree of depigmentation can reliably be assessed by the patient themselves which can be useful in large (epidemiological) studies. Furthermore, this could contribute to the patient's disease insight and therapy loyalty.

Comments: Vitiligo is a common skin complaint that affects patient's appearance and QoL. Until now, a self-assessment tool to assess the degree of depigmentation in vitiligo is not available. SAVASI is a patient-based self-assessment scoring system in vitiligo. This score can be calculated by the patient at home by self or with some help. The body is divided into seven mutually exclusive parts, and the extent of depigmentation and the area of involvement (in hand units) are measured by the patient. SAVASI is calculated as the cumulative sum of the products of extent of depigmentation and area of involvement in each part (possible range 0–100). This study was aimed at determining the practicality of SAVASI. It was shown to take 5–10 min to measure and is simple to calculate. The high correlations of SAVASI with VASI, high inter-rater reliability, and ease of use found in this study make it a practical tool in clinical scenario. Combining SAVASI with disease activity scoring systems such as VIDA can help in obtaining the complete clinical picture. Further studies applying this scoring tool in larger population will be educative.

Amer AA, Gao XH. Quality of life in patients with vitiligo: An analysis of the dermatology life quality index outcome over the past two decades. Int J Dermatol 2016;55:608-14.

Vitiligo is one of the most important skin disorders that do not cause much physical impairment; however, due to its disfiguring appearance, patients have disturbances in mental health and quality of life (QoL). The dermatology life quality index (DLQI), as one of the most specfic QoL instruments, is now used widely for patients with vitiligo. The main objective of this review is to collect and present detailed information about issues and disturbances related to QoL of patients with vitiligo by reviewing the DLQI studies worldwide in the past 20 years. The impact of vitiligo assessed by the DLQI varies according to the clinical and demographic characteristics of patients. In the majority of our reviewed studies, women showed more QoL impairment than men did, as did young patients compared to elderly ones, married women with vitiligo than singles, and patients with involvement on exposed sites than those on unexposed sites. Dark-skinned people showed more life quality effects than white people did. Dermatologists should pay particular attention to such patients who experience insufficient QoL as they require more effort to cure their disease.

Comments: Vitiligo is an acquired pigmentary disorder that affects 1–4% of the world population. Although it does not produce any physical impairment, it adversely affects the QoL. There is a lot of social isolation and stigmatization when it comes to jobs, marriage, etc. The DLQI is a simple 10-question validated questionnaire developed in 1994 by Finlay et al. to assess limitations caused by the impact of skin disease. It was the first dermatology-specific QoL instrument and now is one of the most widely-used questionnaires. The questionnaire is self-administered, simple, easy to complete, designed for use in adults (i.e., patients over the age of 16 years) and contains 10 questions related to patients' symptoms and feelings, daily activities, leisure, work or school, personal relationships, and treatment over the previous 1 week. The variations in QoL between genders, marital status, age, skin color, nationality, and site of involvement play a major role in the treatment seeking practices, research, and social support systems available across the world. It is very important to recognize and address the psychological and social issues of this disease. Dealing with its psychological component is necessary to improve QoL and treatment outcomes.

Griffith RD, Simmons BJ, Bray FN, Falto-Aizpurua LA, Yazdani Abyaneh MA, Nouri K. 1064 nm Q-switched Nd: YAG laser for the treatment of Argyria: A systematic review. J Eur Acad Dermatol Venereol 2015;29:2100-3.

Argyria is a benign skin disease characterized by blue to slate-gray discoloration that is caused by deposition of silver granules in the skin and/or mucus membranes as a result of long-term ingestion of ionized silver solutions or exposure to airborne silver particles. The skin discoloration can be generalized or localized and is exacerbated by sunlight. The skin discoloration is usually permanent, and until recently, there has been no effective treatment for argyria. Over the past 6 years, a number of case reports and one case series have described cases of argyria that was successfully treated with a 1064 nm Q-switched (QS) neodymium-doped yttrium aluminum garnet (Nd: YAG) laser; however, a review of these studies has never been reported in the dermatologic literature. To review the use of the 1064 nm QS Nd: YAG laser for the treatment of argyria, a search of the National Library of Medicine's PubMed Database and the SCOPUS Database was performed to find articles that detailed the treatment of argyria with 1064 nm QS Nd: YAG laser. Six articles were selected for inclusion in this review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd: YAG laser offers a novel and effective treatment for argyria. A systematic review of the dermatologic literature revealed a limited number of case reports and case series using this treatment. However, the results gleaned by the authors from the literature review provide important information to the clinician. For patients with argyria, a single pass of the 1064 nm QS Nd: YAG laser offers immediate, effective, and sustained pigment clearing without any long-term adverse effect.

Argyria is caused by deposition of silver granules in the skin and can be localized or generalized. Silver has been used systemically and topically since centuries for various medical purposes. Today, the cases of argyria occur from use of silver coated sugar, pills, nose or eye drops, silver jewelry, acupuncture needles, silver sulfadiazine cream, and ingestion of silver nitrate. The most common source is homeopathic colloidal silver solution. The silver is deposited all over the body, but the pigmentation is more prominent on sun-exposed sites as sunlight acts as a catalyst for reduction of silver. No effective treatment modalities have been reported in the past. Low fluence QS Nd: YAG laser has shown to be an effective modality for treatment of argyria. There are 6 studies covered in this review with a total of 7 patients, all showing a significant response to treatment. Although the number of patients is low, the results are promising and further studies need to be done in this regard.

Vachiramon V, Panmanee W, Techapichetvanich T, Chanprapaph K. Comparison of Q-switched Nd: YAG laser and fractional carbon dioxide laser for the treatment of solar lentigines in Asians. Lasers Surg Med 2016;48:354-9.

Solar lentigines are benign pigmented lesions that occur mostly on sun-exposed areas. Q-switched (QS) and ablative lasers are effective for removing these lesions, but the high incidence of postinflammatory hyperpigmentation raises concern in darker skin types. The objective of this study is to compare the effiency and degree of postinflammatory hyperpigmentation with the QS neodymium-doped yttrium aluminum garnet (Nd: YAG) and fractional carbon dioxide (CO2) laser for treatment of solar lentigines in Asians. Twenty-five Thai patients (skin phototype III–IV) with at least two lesions of solar lentigines on upper extremities were enrolled in this study. Two lesions were randomly selected for the treatment with a single session of QS Nd: YAG or fractional CO2 laser. Outcomes were evaluated using physician grading scale, colorimeter, and patient self-assessment at 6 and 12 weeks after treatment. Side effects were recorded. A 532 nm QS Nd: YAG laser showed significant improvement of pigmentation over fractional CO2 laser at the 6th and 12th week by both colorimeter assessment and physician grading scale (P < 0.05). No significant difference in postinflammatory hyperpigmentation from both lasers was observed. In terms of patient self-assessment, 80% of the patients treated with 532 nm QS Nd: YAG laser had excellent results compared to 8% in fractional CO2 laser group. However, fractional CO2 laser treatment had faster healing time and less pain score compared to QS Nd: YAG laser. It is concluded that QS Nd: YAG is superior to fractional CO2 laser for treatment of solar lentigines but requires longer healing time and produces more pain. The incidence of postinflammatory hyperpigmentation was not significantly different with both lasers. Further studies are needed to obtain the proper parameter and the treatment frequency of fractional CO2 laser in solar lentigines.

Comments: Solar lentigines develop in adults due to long-term repeated sun exposure leading to melanocyte proliferation and accumulation of melanin within keratinocytes. They affect elderly individuals, and though benign, may be cosmetically disfiguring. The conventional treatment modalities include medical modalities such as hydroquinone, hydroxy acid, and tretinoin-containing products and physical modalities such as cryotherapy, laser therapy, and chemical peels. Both QS lasers and ablative lasers have been used for solar lentigines with good response. However, there is a risk of postinflammatory hyperpigmentation with both lasers and of scarring with ablative CO2 laser. This was a prospective, single-blinded, randomized, intra-individual controlled trial study designed to compare the efficacy and degree of postinflammatory hyperpigmentation from QS Nd: YAG and fractional CO2 laser for treatment of solar lentigines on Asian skin. Two lesions on upper limb were chosen. One lesion was treated with single session of 532 nm QS Nd: YAG, 3 mm spot size, energy fluence of 1.4–1.7 J/cm 2 at 2 Hz until the endpoint was reached (immediate whitening). The other lesion was treated with single session of fractional CO2 laser with a 300 density tip, pulse energy vary from 55 to 70 mJ with 200 spots/cm 2 in the static mode for two passes. The superior efficacy of QS Nd: YAG is compromised by its longer healing time and more pain. However, a change in frequency and other parameters may change the results, especially with fractional CO2 laser and further studies are needed in this regard.

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