|CURRENT BEST EVIDENCE
|Year : 2017 | Volume
| Issue : 2 | Page : 129-132
Current Best Evidence From Pigmentary Dermatology
Tanvi Gupta, Rashmi Sarkar
Department of Dermatology and Venereology, Maulana Azad Medical College and Associated Hospitals, New Delhi, India
|Date of Web Publication||1-Dec-2017|
Department of Dermatology and Venereology, Maulana Azad Medical College and Associated Hospitals, New Delhi 110 002
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;4:129-32
Mutalik S, Shah S, Sidwadkar V, Khoja M. Efficacy of cyclosporine after autologous noncultured melanocyte transplantation in localized stable vitiligo − A pilot, open label, comparative study. Dermatol Surg 2017. doi: 10.1097/DSS.0000000000001190
Vitiligo is a pigmentary disorder having immense cosmetic and social impact. Various treatment modalities have been explored and tried with variable but limited success. The most common setback encountered after vitiligo surgery is the depigmented halo around the treated area (perilesional halo/achromic fissure). This could be attributed to the presence of cytotoxic CD8+ T cells in the perilesional skin. Cyclosporine (CsA) is a calcineurin inhibitor that acts selectively on T cells and has been routinely used in preventing organ transplant rejection. Considering this action of CsA, a pilot, comparative study was undertaken to evaluate whether it has any role in preventing the perilesional halo and achieving uniform, complete repigmentation in the patients of stable vitiligo, after autologous noncultured melanocyte–keratinocyte cell transplant (NCMKT) surgery.
This study was performed at two centers at two different cities in India. Fifty patients of stable vitiligo (stable for >2 years) resistant to conventional therapies were included. All patients underwent NCMKT as per standard procedure. Of the 50 patients, 25 patients (Group I) randomly selected by using alottery method (simple random sampling method) did not receive any topical or oral medications, postoperatively. Remaining 25 patients (Group II) were started on CsA 3 mg/kg/d orally for the first 3 weeks followed by 1.5 mg/kg/d for the next 6 weeks. Each patient from both the groups was reviewed at 4, 8, 12, and 24 weeks after the surgery. At each follow-up visit, laboratory parameters (blood urea and creatinine levels), blood pressure, and the percentage of repigmentation were recorded. All patients completed 6 months’ follow-up. The area of involvement was calculated as per Wallace rule of 9. The repigmentation was graded according to the percentage of area covered as follows: poor: <25%, fair: <50%, good: >50%, and excellent: >75%. Serial photographs taken at each visit were sent to four senior dermatology colleagues to assess the repigmentation.
There was a statistically significant difference between the results obtained from the two groups. The results were significantly better in Group II patients, the CsA group. In Group II, 100% achieved more than 75% repigmentation (median 90.7% repigmentation) at the end of 6 months. Adverse effects were noted in very few patients from Group II and were mild. Two patients experienced headache, two had nausea and vomiting, and one patient had a transient rise in blood pressure (normalized without medication).
Perilesional halo (achromic fissure) is a commonly observed phenomenon in vitiligo patches after tissue or cellular transplant surgery. The highlight of this study is the simplicity of adding an oral immunosuppressive (CsA) to achieve faster, complete, and uniform repigmentation in stable vitiligo after NCMKT, thereby saving time and giving the patients maximum esthetic result. The limitations of this study are as follows: being a pilot study, no other studies were available for comparing and supporting the authors’ results and observations, the sample size was limited, and the study lacks histopathological evidence to demonstrate the CD8+ lymphocytic infiltrate and migration of transplanted melanocytes in the vitiligo perilesional skin (the patients were already worried about the disfigurement caused by vitiligo; hence, they were reluctant to accept a biopsy scar over the treated site). Nevertheless, the results of the study are encouraging. More number of such controlled studies would help to validate the routine use of CsA after NCMKT.
Gordon JR, Reed KE, Sebastian KR, Ahmed AM. Excimer light treatment for idiopathic guttate hypomelanosis: A pilot study. Dermatol Surg 2017;43:553-7. doi: 10.1097/DSS.0000000000000996
Idiopathic guttate hypomelanosis (IGH) is a common, acquired, benign leukoderma that is characterized by multiple, discrete, hypo-, or depigmented 2–5 mm macules. Treatment for IGH is difficult; small studies have reported a successful treatment with modalities such as topical pimecrolimus, tacrolimus, tretinoin, superficial dermabrasion, cryotherapy, 88% phenol, nonablative fractional photothermolysis, and fractional carbon dioxide laser. Evidence-based studies for these modalities are lacking; thus, there is no “gold standard” for the treatment of IGH. Monochromic excimer light (308 nm) has been used as the treatment for the disorders of pigmentation such as vitiligo. Although the underlying mechanism of IGH is unknown, the authors hypothesize that melanocytic stimulation from excimer light will result in repigmentation of IGH.
Subjects were evaluated to determine a Fitzpatrick score and selected five IGH lesions on each leg that appeared as the best representative lesions. Photographs were taken to measure baseline pigmentation, and the subject was randomized to either their right or left lower extremity for treatment. The XTRAC excimer laser (wavelength of 308 nm) was performed using the standard vitiligo protocol of twice-weekly treatments for 12 weeks. Subject self-reported improvement surveys and photographs were collected at weeks 4, 8, and 12. Efficacy was determined by comparing baseline photos with follow-up photos by two independent dermatologists, who were blinded to the visit number and treatment side. Efficacy was assessed by improvement from baseline using the following scale: 1 = worsening of IGH; 2 = no improvement (IGH remained stable); 3 = mild improvement of IGH (some repigmentation on <50% IGH); 4 = moderate improvement (some repigmentation on >50% or full repigmentation on <75% IGH); 5 = full repigmentation on >75% IGH which was then converted to −1, 0, 1, 2, and 3, respectively. An internal control was represented by marked lesions on the nontreated extremity of each patient. Control versus treatment groups were statistically compared using a descriptive trend analysis.
Treated IGH lesions had a significantly higher repigmentation by the end of the study. A significant improvement was seen in both excimer-treated and untreated lesions in the first 4 weeks of treatment. After week 4, excimer treated lesions continued to show improvement, significantly increasing their repigmentation by week 12. No significant continued repigmentation was observed in the untreated lesions. There were no adverse events during this study.
Various modalities have reported successful treatment of IGH in small studies and case reports, however, this is the first report of excimer for treatment of IGH. It is thought that excimer promotes repigmentation through immunosuppression and immunomodulation of the skin. This is the first study to show successful repigmentation of IGH lesions using excimer therapy. The outcomes are rather remarkable. Limitations included a small sample size with minimal variation in Fitzpatrick skin type, an all-female pool, and lack of extended follow-up. Graded observations of blinded investigators and subject self-assessment scales were used as a measurement for improvement. Long-term follow-up would be recommended in future studies to evaluate if the results are long-lasting and to see if further repigmentation can be achieved by extending the treatment period beyond 12 weeks.
Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, Turkowski Y, et al. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol 2017;76:1054-60.e1. doi: 10.1016/j.jaad.2017.02.049
Vitiligo is an autoimmune disorder in which an acquired loss of functioning melanocytes results in depigmented patches of skin. Recent chemokine expression profiling performed in human lesional skin has revealed a predominantly T-helper1-mediated signature with elevated levels of interferon (IFN)-g and its associated chemokines CXCL9 and CXCL10. In vitiligo mouse models, treatment with neutralizing antibodies of CXCL10 or IFN-g induced reversal of vitiligo lesions. Inhibiting IFN-g or its downstream effectors such as Janus kinases (JAKs) may be an effective strategy for vitiligo treatment development.
JAKs are a family of intracellular nonreceptor tyrosine kinases that are critical for IFN-g signaling. The primary goal of the study was to determine if topical ruxolitinib use is associated with vitiligo skin repigmentation as determined by significant improvement in the Vitiligo Area Scoring Index (VASI).
Patients were treated with topical ruxolitinib 1.5% cream for twice-daily use on their vitiligo patches, excluding perioral and periocular areas, for 20 weeks. A minimum of 1% body surface area (BSA) affected by vitiligo was required for inclusion at screening. Topical application of ruxolitinib was limited to 10% BSA, or maximum 3.75 g per application, to minimize systemic exposure. Patients with greater than 10% affected BSA were limited in their drug application to specific body locations mutually agreed on by the patient and the principal investigator. The primary outcome was improvement in the VASI at week 20. Multiplication of affected BSA (estimated with the use of hand units) by the degree of depigmentation (0–100%) within each hand unit was performed to calculate a VASI score (possible range, 0–100). Total BSA was calculated with the use of a handprint (palm plus the volar surface of fingertips) to estimate 1% BSA. Photographs of vitiligo patches were taken at all study visits to help monitor clinical progression.
Statistically significant mean percent improvement in overall VASI score of 23% (95% CI, 4–43%; P = 0.02) was observed for all enrolled patients (n = 11), corresponding to a mean VASI score of 9.8 at baseline and 8.9 at week 20. Percent change in individual VASI scoring ranged from 0 to 98%. A percent improvement in overall mean VASI score of 27% (95% CI, 4–50%; P = 0.02) was observed for patients who completed the trial. None of the existing vitiligo patches at baseline worsened. Few mild side effects were noted.
Topical JAK inhibition may offer a promising new treatment for vitiligo. Limitations of this study include the small sample size and the open-label study design. Natural sun exposure was not monitored in the subjects. The study was conducted in Boston from January through August; thus, natural sunlight could have contributed indirectly to vitiligo improvement. Also laboratory monitoring was not performed in the patients, so it cannot be commented on potential laboratory-adverse events, but it was assumed that these were not likely to occur with topical application. Even with a small number of patients, a meaningful change in vitiligo repigmentation was noted. Future studies should be aimed at conducting large-scale, randomized, controlled trials to better understand the efficacy and adverse events of topical JAK inhibitors in vitiligo.
Xu Y, Ma R, Juliandri J, Wang X, Xu B, Wang D, et al. Efficacy of functional microarray of micro-needles combined with topical tranexamic acid for melasma: A randomized, self-controlled, split-face study. Medicine (Baltimore) 2017;96:e6897. doi: 10.1097/MD.0000000000006897
Melasma is an acquired disorder of melanogenesis appearing as localized and chronic hypermelanosis of the face. Because the pathogenesis of melasma is incompletely understood, the effects of topical drugs and lasers are often less than satisfactory. Tranexamic acid (TA), a plasmin inhibitor, is reported to improve melasma when administrated orally or injected locally. The effectiveness of topical TA is debated and doubted, because the water-soluble nature of TA limits its transepidermal absorption. A better and less invasive method is required to enhance absorption of topical TA and replace the need for repeated painful intradermal injections. Microneedles (MNs) can provide a minimally invasive way for transdermal delivery A functional microarray of MNs is a new type of MNs, which consists of 36 MNs (250 mm in height) over an area of 5 × 5 mm. The MN depth is similar to that of the epidermis, so the microarray does not penetrate the dermis and is, therefore, painless. The diameter of the tip of each needle is only 80 nm, which takes this skin penetration technology one step closer to an almost noninvasive level. The current study evaluated the effectiveness and possible side effects of topical TA for melasma with or without pre-treatment using a functional microarray of MNs.
A total of 30 females with melasma (age range, 20–50 years) with Fitzpatrick skin type III to IV were enrolled. The microarray is connected to a pen-like vibrator, which causes the microarray to penetrate the skin with a frequency of 3000 times per minute. The left or right side of the face was chosen randomly as the treated side and the other side as the control. The sides were pre-treated with the microarray of MNs or a sham device, respectively. First, 0.5% TA injection solution was applied all over the face to keep the skin wet. The pen-like vibrator was then moved smoothly and slowly on the surface of the skin, allowing the MN or sham device to stay at the same location for approximately 3 s. After completing the treatment, both sides of the face were covered with gauze soaked with the 0.5% TA solution for another 10 min. This treatment was repeated once per week for a total of 12 weeks. At baseline and at 4, 8, and 12 weeks after beginning treatment, photographs of both sides of the face were taken by Visia and scores of brown spots on each side of the face were recorded. In vivo erythema, melanin, transepidermal water loss, elasticity, skin surface roughness, and hydration were measured with the corresponding probes of the MPA9. Two blinded physician observers evaluated the clinical improvement by photographs taken of both sides of the face. At the end of the 12-week treatment period, the participants were asked to evaluate their satisfaction with the effects on both sides of the face. Adverse events, including erythema, scaling, erosion, itching, and burning, were recorded at each visit.
Clinical manifestations of melasma improved at 12 weeks after combined therapy of MNs with TA, appearing as lightening and a diminished area of melasma, especially at week 12. By contrast, the pigmentation exhibited no obvious change on the control side. Brown spots improvement, melanin index, erythema index, physician assessment, and subjective assessment were all better on the TA plus MNs side as compared to the control side.
TA is one of the treatment strategies for melasma that has been a focus of attention in recent years. To avoid systemic administration of TA, localized microinjection of TA has been used for melasma. The present study shows promising results. One limitation of study was that TA injection solution was used in place of a topical preparation. In the present study, melasma area severity index (MASI) was not used. Another limitation of study was the observation period of only 3 months; long-term follow-up is required to confirm the efficacy results and to evaluate relapse rates. More studies are required before a conclusion can be reached.
Handjani F, Aghaei S, Moezzi I, Saki N. Topical mycophenolate mofetil in the treatment of vitiligo: A pilot study. Pract Concept 2017;7:6. doi: 10.5826/dpc.0702a06
Vitiligo is characterized by circumscribed, depigmented macules and patches of skin. It is a multifactorial disorder due to genetic and environmental factors. The autoimmune-mediated destruction of melanocytes is a well-accepted theory and is currently the leading hypothesis in vitiligo pathogenesis. Mycophenolate mofetil (MMF) inhibits deoxyribonucleic acid (DNA) synthesis in lymphocytes and inhibits the production of antibody by B-cells. The drug prevents not only glycosylation and expression of binding molecules but also the summoning of lymphocytes and monocytes into sites of inflammation. Therefore, the use of it could theoretically help in the management of vitiligo.
Thirty patients were enrolled in this pilot study. The patients were instructed to apply topical MMF 15% preparation twice daily for 3 months, and at the end of every month repigmentation was assessed using the Vitiligo Area Scoring Index for every patient.
At the end of third month, 36.6% (n = 11) of patients achieved approximately 25% repigmentation. At the end of first month, only one patient had dramatic response with 40% repigmentation, but at the end of second month, five patients (16.6%) had achieved 25% repigmentation. Comparing the overall pigmentation at the end of the second month with the first month showed a statistically significant difference (P value = 0.027). Comparing the overall pigmentation at the end of the third month with the first month showed a statistically significant difference (P value = 0.005). None of the patients presented with any adverse side effects while using the topical medication.
The role of MMF has not been studied much in vitiligo. The results of this study are not remarkable, yet these warrant further research. The limitation of the study is that the number of cases is less, and there is no control group. Further, randomized clinical trials with larger sample sizes are needed to assess the efficacy of topical MMF in the treatment of vitiligo.
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