|SPECIAL SECTION: CURRENT BEST EVIDENCE
|Year : 2017 | Volume
| Issue : 1 | Page : 56-60
Current best evidence from pigmentary dermatology
Tanvi Gupta MD, DNB, Senior Resident , Rashmi Sarkar
Department of Dermatology & VD, Maulana Azad Medical College, New Delhi, Delhi, India
|Date of Web Publication||19-Jun-2017|
Department of Dermatology and Venereology, Maulana Azad Medical College and Associated Hospitals, New Delhi 110 002, Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta T, Sarkar R. Current best evidence from pigmentary dermatology. Pigment Int 2017;4:56-60
Arora S, Kar BR. Reduction of blister formation time in suction blister epidermal grafting in vitiligo patients using a household hair dryer. J Cutan Aesthet Surg 2016;9:232-5. doi: 10.4103/0974-2077.197045
Suction blister epidermal grafting (SBEG) is a simple and effective way of surgical repigmentation in the cases of vitiligo, and it does not cause any scarring at the donor site. The major problem faced during the procedure is the time taken for the formation of blisters. Temperature at the suction site is one of the factors affecting the blister formation time. Wood’s lamp and infrared lamp have been used previously for faster induction of suction blister formation. A hair dryer was used in this study to increase the surface temperature at the suction site and to reduce the blister formation time.
This was a left–right comparison study conducted in vitiligo patients. Totally, seven patients with vitiligo involving both the angles of the mouth and the adjacent lower lip were enrolled. All the patients had stable vitiligo lesions. Suction syringes were applied on both the thighs of all the patients. On the right thigh, blisters were raised as per the procedure standardized by Gupta et al. On the left thigh, a similar procedure was used, but a hair dryer (Philips HP 8100, 1000 W) was used additionally to raise the surface temperature of the skin to 44°C. The hair dryer was blown, once every 10 min, for 1 min from a distance of 1 foot to raise the surface temperature to the desired level. The surface temperature was recorded using an infrared thermometer once every 10 min (i.e., after blowing with the hair dryer) from the intervening skin between the two suction syringes. The time taken for the formation of a well-formed, dome-shaped, unilocular blister was noted. The standard procedure of suction blister grafting was then followed at the recipient site. All the patients were started on topical Psoralen Ultraviolet A phototherapy using sunlight (PUVASOL) after SBEG and followed up after 2 months. Two-tailed P value was used for statistical analysis.
The mean time taken for the formation of a blister on the right thigh was 121.1 ± 6.2 min, and the mean time taken for blister formation on the left thigh was 69.6 ± 5.4 min. The decrease in blister formation time on the left thigh, where the surface temperature was raised with the help of a hair dryer, was statistically significant as compared to the right thigh. All the patients showed uniform repigmentation of the grafted sites, with no color mismatch from the surrounding skin. There were no adverse effects noted.
| Comment|| |
One of the major drawbacks of suction blister grafting is the time taken for the formation of a blister. The optimum temperature described for the formation of blister in various studies is 40–45°C. Faster blister formation had been demonstrated using an infrared lamp of 150 W and a Wood’s lamp for 20 min in separate studies. The present study used the help of a hair dryer to raise the surface temperature of the suction site, which is a very simple, easily available, and well affordable instrument; in addition, the time saved during the procedure is quite significant.
The results of the present study are quite intriguing and interesting. As this was a left–right comparison study, that is, a self-controlled study, the time-independent confounding variables were eliminated. There are three drawbacks in the study. First is the small sample size of the study. Second, it is not clear which of the blisters (right or left) were used for grafting, and thus, the results could be misunderstood. And lastly, no standardized method for evaluating repigmentation was used. More studies with a larger sample size and of higher quality should be conducted to verify the conclusions of this study.
Yue B, Yang Q, Xu J, Lu Z. Efficacy and safety of fractional Q-switched 1064 nm neodymium-doped yttrium aluminum garnet laser in the treatment of melasma in Chinese patients. Lasers Med Sci 2016;31:1657-63
Melasma is an acquired disorder of hyperpigmentation, with its treatment being a challenge. A variety of therapeutic approaches including topical formulations, chemical peels, oral medication, lasers, and light sources are used. On the basis of the theory of selective photothermolysis, Q-switched (QS) lasers have proven effective for melasma. Fractional mode has been developed in recent years, and this prospective study was conducted to explore the clinical efficacy and safety of fractional mode Nd:YAG laser in treating melasma in Chinese patients.
Thirty patients with mild-to-severe melasma with the skin types III or IV were recruited and treated with a fractional, QS Nd:YAG laser at a wavelength of 1064 nm, with a spot size of 8.5 mm × 8.5 mm containing 25 dots. The diameter of each dot was 1.25 mm, and the area of coverage was 42.4%. Eight sessions of treatment at 2–3-week interval were performed on each patient. The laser parameters used were 800–1100 m J/P (approximately 2.6–3.6 J/cm2) of fluence and repeated frequency of 2 Hz. Sunscreen with a sun protection factor greater than 30 and PA+++ was applied daily on the whole face during the entire study. Clinical photographs were taken using the Visia skin analysis imaging system and a digital camera as well. An evaluation of melasma lesions was performed before each treatment session and 4 and 12 weeks after the final treatment using the modified Melasma Area and Severity Index (MASI) by Kimbrough-Green and colleagues. The Melanin Index (MI) and Erythema Index values of the lesion were measured using a Mexameter. Physician’s global assessment and patients’ self-assessment were also performed. Recurrence rate was estimated and safety evaluation was performed. All the statistical analyses were performed using statistical package for the social sciences (SPSS) 16.0 software, and P < 0.05 was regarded as statistically significant.
Mean MASI score decreased dramatically from 12.84 ± 6.89 before treatment to 7.29 ± 4.15 4 weeks after the final treatment (Z = −4.541, P < 0.01), with 43% improvement from the baseline MASI score. Mean MI decreased with time, and changes paralleled the clinical improvement. Relapse rate was 40%. Overall, the laser treatment was well tolerated. This study concluded that Pixel QS Nd:YAG laser therapy is efficacious for the treatment of melasma. Although the efficacy is no better than the conventional low-fluence QS Nd:YAG laser, the recurrence rate of this therapy is much lower.
| Comment|| |
The efficacy of QS laser treatment for pigmentary lesions is based on the theory of selective photothermolysis. The large spot size, low fluence-mode application of the 1064-nm QS Nd:YAG laser is now a widely used therapy for melasma, especially in Asians. Previous studies have shown beneficial effect; however, the recurrence rate was high if weekly treatment was performed with relatively high fluence. The risk of hyperpigmentation increases with the number of treatments.
The results of this study are encouraging in the sense that low relapse rates were noted. In addition, no hyper- or hypopigmentation was noted in the patients. The results are to be evaluated with caution and cannot be extrapolated to the Asian population as a whole, because no patients of darker skin types were included. In addition, the number of patients is too low to be statistically significant, and the follow-up period seems to be inadequate. More studies including the skin types V and VI with longer follow-up periods should be conducted before making a sweeping statement about the study results.
Shi MH, Wu Y, Li L, Cai YF, Liu M, Gao XH, et al. Meta-analysis of the association between vitiligo and the level of superoxide dismutase or malondialdehyde. Clin Exp Dermatol 2017;42:21-29. doi: 10.1111/ced.12950
The precise pathogenesis of vitiligo has not been clarified. In recent decades, it has been suggested that the overproduction of reactive oxygen metabolites and/or the limited production of antioxidants might trigger melanocyte destruction. The production of reactive oxygen species (ROS) can lead to an alteration in the cellular redox state, with an increase in superoxide dismutase (SOD) activity as a compensatory mechanism. Malondialdehyde (MDA) is an end product of lipid peroxidation induced by ROS and can be considered a major manifestation of oxidative stress. This meta-analysis of the published studies was conducted to investigate the relationship between vitiligo and SOD or MDA to obtain evidence for the usefulness of antioxidants in vitiligo. Relevant articles written in English or Chinese and published before October 2015 were identified through a search of the PubMed, China National Knowledge Infrastructure, Web of Science, Cochrane Library, Wan Fang Med Online, Chinese Biology Medical Literature, and VIP databases using the following search keywords: “superoxide dismutase” OR “SOD” OR “malondialdehyde” OR “MDA” AND “vitiligo.” Eligible studies had to include the following: patients with vitiligo and a healthy control group; outcome measures with quantitative SOD or MDA levels [mean ± standardized mean difference (SMD)]; and the sample source being the blood, the plasma/serum, the erythrocytes, or the skin. Studies were excluded if they included the following: animal or in vitro experiments or case reports; had data that was duplicated in another study; did not contain original data; had no control group; involved <30 participants in total; or had low methodological quality. Two of the authors independently extracted data from eligible studies using a standardized form. Disagreements were resolved through discussions and a careful reexamination of the full text by a third author. The quality of the included studies was independently assessed by two of the authors, based on the Newcastle–Ottawa Scale. All the statistical analyses were performed with Stata software. The extracted data were used to perform meta-analyses to obtain the SMD and 95% confidence intervals. The statistical significance of SMD was analyzed by the z-test and P < 0.05 was considered statistically significant.
A final total of 32 articles (16 each for SOD and MDA) qualified for meta-analysis, of which 10 articles involved both SOD and MDA levels. The subgroup analyses indicated that the patients with either active or stable vitiligo had higher SOD and MDA levels compared with the controls. Further subgroup analysis showed that the patients with vitiligo had higher SOD levels in the blood and the erythrocytes but lower levels in the plasma/serum, whereas no difference was seen in the skin. MDA levels were higher in the blood/plasma/serum and the skin with no difference in the erythrocytes. The study found a significant association between vitiligo and the high levels of both SOD and MDA. However, the evidence was more inconsistent for SOD than for MDA.
| Comment|| |
The documented data on the levels of SOD and MDA in the patients with vitiligo are inconsistent. In the present meta-analysis, higher levels of both SOD and MDA were observed in the patients of active as well as stable vitiligo indicating the presence of oxidative stress. The plasma/serum showed decreased SOD and increased MDA levels in the patients with vitiligo compared with the controls. Superoxide is one of the most important radicals in lipid peroxidation. Decreased SOD activity could be responsible for the increase of superoxide radicals, which may in turn explain the increased level of MDA. Analysis in the erythrocytes showed a significant association between higher SOD level and vitiligo. The outcomes of the study show possibilities and justify the role of antioxidant therapy in vitiligo to some degree; conversely, the results were varied for SOD because of the heterogeneous ethnicities of the study population. In addition, this was a relatively small analysis, with only 1958 participants from 32 studies; the limited number and small sample sizes of the published studies may have limited the statistical power to prove authentic associations. Second, heterogeneity could not be excluded, because of methodological diversity between the studies. Limitations in identifying significant differences may have been caused by difference in the vitiligo stage or by interassay and interlaboratory variability in the measurements of SOD or MDA levels. Finally, Egger linear regression test showed evidence of publication bias for MDA, which could have been because of the fact that negative results were not published. Thus, more studies are necessary before any further assumption can be made.
Li R, Qiao M, Wang X, Zhao X, Sun Q. Effect of narrow band ultraviolet B phototherapy as monotherapy or combination therapy for vitiligo: A meta-analysis. Photodermatol Photoimmunol Photomed 2017;33:22-31. doi: 10.1111/phpp.12277
Vitiligo is a common skin disease characterized by localized or generalized depigmented macules or patches. The treatment of vitiligo is a challenge for dermatologists. Among the various therapeutic strategies, phototherapy with NB-UVB is considered the first treatment choice for generalized vitiligo. However, NB-UVB does not always bring satisfactory results. Few studies suggest that topical agents may produce synergistic effects when combined with narrow band ultraviolet B (NB-UVB) phototherapy, whereas others do not. Because of these contradictory results, this meta-analysis of all relevant randomized controlled trials (RCTs) was performed to obtain a more reliable conclusion and provide some guidance for treating vitiligo. PubMed, EMBASE, Cochrane Library (from inception to March 2016), and Web of Science (from 1950 to March 2016) were searched for the keyword “NB-UVB” or “narrow band ultraviolet B” combined with the Medical Subject Heading “Vitiligo.” The search strategy was “NB-UVB” or “narrow band ultraviolet B” and “Vitiligo.” The reference lists of all relevant articles were searched for additional information. Trials included comprised any of the following criteria: (i) studies must be clinical RCTs; (ii) the participants of the study must be diagnosed with vitiligo; (iii) they must include NB-UVB monotherapy (or with placebo) for one group and the combination of NB-UVB with any topical agent (topical cancineurin inhibitors (TCIs) or vitamin D analogues (VDAs)) for another group; and (iv) the main outcome measures of the study must include the proportion of ≥50% repigmentation or ≥75% repigmentation. Trials excluded comprised any of the following criteria: (i) irrelevant studies; (ii) controlled but nonrandomized trials; (iii) repeated studies; (iv) without the main outcome measures defined in the inclusion criteria; and (v) retrospective studies. The two investigators extracted data independently and disagreements were resolved by discussion between the two investigators or consensus with another investigator.
The primary outcome of interest was the proportion of a clinical significant response (≥50% repigmentation). The secondary outcome was the proportion of an excellent response, defined as 75% or more repigmentation (≥75% repigmentation) of each lesion in a patient of vitiligo after treatment. The meta-analysis was performed using Review Manager; main outcomes used relative risk and its 95% confidence interval. A probability level less than 0.05 (P < 0.05) was considered statistically significant. A total of seven studies were included in this meta-analysis with a total of 240 patients and 413 lesions. The analysis failed to show a significant better effect of topical calcineurin inhibitor combined with NB-UVB versus NB-UVB alone in ≥50 and ≥75% repigmentation outcomes. The meta-analysis showed that combination therapy with NB-UVB and topical vitamin-D3 analogs had no significant effect in repigmentation ≥50 and ≥75% for the treatment of vitiligo. However, lesions located on the face and the neck had a better ≥50 and ≥75% repigmentation with NB-UVB and topical calcineurin inhibitor combination therapy versus NB-UVB monotherapy. The analysis concluded that adding neither topical calcineurin inhibitors nor vitamin-D3 analogs on NB-UVB could yield significantly superior outcomes than NB-UVB monotherapy for the treatment of vitiligo. However, this meta-analysis showed that the addition of topical calcineurin inhibitors to NB-UVB might increase treatment outcomes in vitiligo affecting the face and the neck.
| Comment|| |
NB-UVB has emerged as a promising treatment for generalized vitiligo. UVB seems to inhibit the effect of cytotoxic T lymphocytes and stimulate melanocyte migration and proliferation. Calcineurin inhibitors and vitamin D analogs are also quite effective in vitiligo. The results of this meta-analysis are fairly informative in the sense that unnecessary adding topical therapies to NB-UVB is not desirable as it may be cumbersome and also add to the cost of therapy; however, the application of calcineurin inhibitors might help in pigmentation over the face and the neck. Yet, there is a theoretical risk of carcinogenesis with the combined use of NB-UVB and topical calcineurin inhibitors; therefore, they need to be applied with caution for short periods only. This meta-analysis has its limitations. First, several trials were excluded because they were not RCTs, although they offered the data we desired. Second, some RCTs were excluded because they did not offer the data desired. In addition, the mean patient age and the mean duration of disease were inconsistent among the studies, and therapies varied in duration and frequency of treatment in these studies. In addition, because of the low power, there was no strong evidence to clarify the results, and we require a larger sample to affirm its reproducibility. More large-scale, high-quality, double-blind RCTs regarding the efficacy of topical agents plus NB-UVB combination therapy are required.
Vanderweil SG, Amano S, Ko WC, Richmond JM, Kelley M, Senna MM, et al. A double-blind, placebo-controlled, phase-II clinical trial to evaluate oral simvastatin as a treatment for vitiligo. J Am Acad Dermatol 2017;76:150-1.e3. doi: 10.1016/j.jaad.2016.06.015
Vitiligo is an autoimmune disease caused by autoreactive CD81 T lymphocytes that target melanocytes, and interferon-induced CXCL10 plays an important role. Simvastatin inhibits interferon signaling by blocking the activation of STAT1 and prevented and reversed the disease in a mouse model. A case report described a patient with vitiligo who was repigmented with simvastatin. We conducted a small, randomized, double-blind, placebo-controlled, phase II clinical trial to test simvastatin as a treatment for vitiligo. After obtaining informed consent, men aged 18–64 years with vitiligo affecting 3–50% of their body surface area (BSA) were enrolled. The patients with a segmental presentation, those already taking a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor, those with existing thyroid disease, and women, based on their increased risk of simvastatin-induced myopathy, were excluded.
Fifteen patients were randomized to receive either 40 mg of simvastatin daily for the first month and 80 mg for the remaining 5 months of the study period, or placebo. Topicals were discontinued for at least 2 weeks, oral immunomodulators for 4 weeks, and phototherapy for 8 weeks before enrollment. Treatment response was measured using the following four outcome measures: (1) Vitiligo Area Scoring Index (VASI) score, (2) change in the size of a “sentinel” patch, (3) investigator global assessment, and (4) subject global assessment. Serum CXCL10 was also measured.
The treatment group experienced an average worsening of disease, with a 26% increase in the mean VASI, whereas the placebo group had a 0% change in the mean VASI; however, the difference between the groups was not significant (P value = 0.094). Neither the changes in the sentinel patch nor the mean investigator global assessment or subject global assessment was significantly different between the groups. Simvastatin did not affect the serum CXCL10 levels. The most common side effects of simvastatin were self-limited myalgia in four participants and diarrhea in two participants. Three participants had mild, transient transaminitis, and four had mild creatine phosphokinase elevations, with none requiring dose modifications. Only one withdrawal, because of vertigo, was thought to be treatment-related. This study does not support the use of oral simvastatin for the treatment of vitiligo.
| Comment|| |
Vitiligo management is a challenge for the dermatologist because of the treatment failures, recurrence, and failure to achieve complete pigmentation while avoiding major treatment-related complications. The search for novel therapeutic options in vitiligo is constantly going on, some of which show promise in case reports but fail to do so in larger studies. The same may be the case with simvastatin. However, the drug should not be dismissed on the basis of the current study alone. Failure to show efficacy in the current study may have been influenced by long-standing disease in the participants (responses are best in those with recent onset), small sample size, or the lack of sensitive measures of treatment response. The VASI relies on an estimation of affected BSA, with limited sensitivity to change (4.7% BSA). Newer outcome measures may provide more sensitive options for monitoring responses. Simvastatin may induce myopathy at higher doses; however, topical treatment may allow the delivery of sufficiently high local concentrations without systemic toxicity and could be tested in larger studies.
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