|CURRENT BEST EVIDENCE
|Year : 2018 | Volume
| Issue : 1 | Page : 60
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||29-May-2018|
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 2018;5:60
Joshipura D, Alomran A, Zancanaro P, Rosmarin D. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: A 32-week open label extension study with optional narrow-band ultraviolet B. J Am Acad Dermatol; 2018. doi: 10.1016/j.jaad.2018.02.023
JAK-inhibitors have shown promise in the treatment of vitiligo. With topical ruxolitinib cream, response was predominantly seen in facial vitiligo. The original study was extended further for 32 weeks with an objective to determine whether continued use of topical ruxolitinib would cause repigmentation in locations that previously did not respond. The primary end-point was an improvement in Vitiligo Area Scoring Index (VASI) at 52-weeks.
Patients continued to be treated with twice daily application of topical ruxolitinib 1.5% cream on areas predetermined at baseline. Application of the cream was limited to 10% body surface area (BSA) or 3.75 g per application. On the basis of previous evidence for the synergism of JAK42 inhibitors and ultraviolet light, concomitant NBUVB treatment was permitted. A statistically significant mean improvement in overall VASI of 37.6% ± 31.2 (P = 0.011) was observed for enrolled patients (n = 8) at week-52 from baseline. Five of eight patients had a treatment response. In patients with >0.5% facial surface area affected (n = 4), a statistically significant mean improvement of 92% ± 7.1 (P = 0.0001) in facial VASI was seen at week-52 with one patient showing complete repigmentation. Three of six patients responded on nonacral upper extremities with a VASI improvement of 12.6% (52 ± 19.5) of whom two were being treated with combination phototherapy. Mean improvement of 16.7% ± 35.6 was seen in Physician Global Vitiligo Assessment, improvement in mean Dermatology Life Quality Index was 1.5, and the change in BSA was 20.78 ± 35.35 at week-52, yet none of them being statistically significant. Five patients, who completed the trial, were followed up at 6-months after treatment discontinuation, and all of them maintained response, with maximum duration of over 40-weeks.
Minor adverse events including erythema in three of the eight patients and transient acne in two patients were observed. Limited response was seen in additional 32-weeks, but an improvement was noted with NBUVB and topical ruxolitinib combination. In conclusion, patients with vitiligo, who used topical ruxolitinib 1.5% cream twice daily with optional NBUVB saw a statistically significant mean improvement in overall VASI score at week-52, and this effect was most pronounced for those treating facial vitiligo.
Janus kinase inhibitors are the newest drugs on the block for vitiligo with promising results. This study was conducted with the purpose of observing whether adding phototherapy will enhance the results of Janus Kinase inhibitors alone. Results are encouraging and the improvement noted in few patients was remarkable with facial lesions improving the most. Also, not many side effects were reported. The study made note of enhanced response to ruxolitinib when combined with phototherapy. Limitations of the study include open-label design, a small sample size, and inability to monitor natural sun exposure. More number of such controlled studies would help to validate the routine use of phototherapy combined with ruxolitinib.
Sobhi RM, Sharaoui I, El Nabarawy EA, El Nemr Esmail RS, Hegazy RA, Aref DH. Comparative study of fractional CO2 laser and fractional CO2 laser-assisted drug delivery of topical steroid and topical vitamin C in macular amyloidosis. Lasers Med Sci; 2018. doi: 10.1007/s10103-018-2457-1
Macular amyloidosis (MA) represents a common variant of primary localized cutaneous amyloidosis. It has a characteristic female predominance; none of the treatment modalities described is either curative or uniformly effective in patients with MA. This study to determine the effect of fractional CO2 laser in MA in comparison to fractional CO2 laser-assisted drug delivery of topical steroids and topical vitamin C included 10 female patients with cutaneous MA aged between 20 and 62 years. Patients were treated with four sessions of fractional CO2 laser with 4 weeks interval. Laser treatments were performed using fractional CO2 laser with the following parameters (power 18 W, spacing 800 μm, dwell time 600 μs, stacking 3). The lesion was divided into three areas: area 1, treated by fractional laser only; area 2, treated by fractional laser followed by topical corticosteroid application under occlusion for 24 h; and area 3, treated by fractional laser followed by topical vitamin C serum application under occlusion for 24 h. All lesions were examined clinically and histologically before the therapy and 1 month after the end of the therapy to evaluate the degree of improvement. All the treated areas showed a significant decrease in pigmentation score after treatment, significant drop in rippling (P value <0.016), and improvement of lichenification; as regards the histological improvement, there was a significant decrease of the amyloid amount after treatment. As regards the amyloid amount, results showed significant decrease in the amount of amyloid in all of the three treated areas. Area 2 reported the highest decrease in the amyloid amount followed by areas 1 and 3. One patient (10%) was highly satisfied by the treatment, 6 (60%) reported moderate degree of satisfaction, while only 3 (30%) reported mild satisfaction. Minimal complication occurred in the form of postinflammatory hyperpigmentation in one patient. None of the patients suffered pain, ulceration, or infection. Fractional CO2 alone can be used to improve the texture of MA. If used to assist the delivery of topical steroids and topical vitamin C, improvement can be highly increased.
Various modalities have been tried in MA but none has been successful. The area treated with steroids and laser showed the best results as expected as the laser based on the principle of fractional thermolysis acts on the amyloid deposit in the dermis whereas the steroid acts by improving the pruritus and the associated lichenification. The vitamin C serum may not be penetrating the thick skin and thereby not as effective. The study is limited because of the less number of patients, being uncontrolled open label and for lacking follow up. Long-term follow-up would be recommended in future studies to evaluate if the results are long-lasting.
Arbache S, Roth D, Steiner D, Breunig J, Michalany NS, Arbache ST, et al. Activation of melanocytes in idiopathic guttate hypomelanosis after 5-fluorouracil infusion using a tattoo machine: Preliminary analysis of a randomized, split-body, single blinded, placebo controlled clinical trial. J Am Acad Dermatol 2018;78:212-5. doi: 10.1016/j.jaad.2017.08.019
This study presents a preliminary analysis of the first eight patients who have completed a randomized clinical trial for idiopathic guttate hypomelanosis (IGH) treatment that was approved. The rationale for this study was the preliminary histologic analysis of IGH spots, in which the authors observed varying degrees of papillary dermis fibrosis. Fulton et al. described the repigmentation of hypopigmented scars arising from different etiologies after mechanical removal of dermal fibrosis. The formulated hypothesis was that IGH repigmentation could occur if the underlying dermal fibrosis was removed. Instead of mechanically removing this fibrosis, it was attempted to remove or reduce it by delivering medication with antifibrotic properties. Because of its low cost, injectable 5-fluorouracil (5-FU) was the drug of choice. The drug delivery technique used in this clinical trial was named MMP [the Portuguese acronym for microinfusão de medicamentos na pele (i.e., microinfusion of drugs into the skin)]. This technique drew inspiration from the ancient art of tattooing. In MMP, the tattoo machine’s needles convey the medication contained in the sterile needle cartridge into the skin, i.e., the microneedling and injection processes occur simultaneously. Needling depth is gradually adjusted until mild pinpoint bleeding is achieved, which is an indication that the dermis has been reached. The intervention was made using a Cheyenne tattoo machine by MT. DERM (Berlin, Germany), the only equipment of the sort approved by the Brazilian Health Agency (ANVISA) for medical use. The data show that IGH repigmentation after 5-FU MMP treatment was statistically higher when compared with placebo MMP (75.3% 5-FU repigmentation vs. 33.8% placebo, P < 0.001). The authors believe that 5-FU MMP treatment may be beneficial in treating IGH.
The study has interesting results. Even though no adverse effects were observed in MMP-treated patients, the safety and efficacy of this 5-FU drug delivery method needs to be proven by means of additional studies. The study has a split body study design, where the control is the same patient, thus, removing any confounding factors and, thus, the bias. While area treated with only MMP showed 33.8% pigmentation; the area with MMP-5-FU showed 75.3% pigmentation, which was statistically significant. So though MMP alone might result in improvement, the results are better when combined with 5-FU. This is a new innovative technique of drug delivery system and the study results are encouraging. The limitations are less number of patients, limited follow-up, and being nonrandomised uncontrolled trial. Even with a small number of patients, a meaningful change in IGH repigmentation was noted. Future studies should be aimed at conducting large-scale, randomized, controlled trials to better understand the efficacy and adverse events of this therapy in IGH.
Badawi AM, Osman MA. Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma. Clin Cosmet Investig Dermatol; 2018. doi: 10.2147/CCID.S147413
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. Ablative fractional laser (AFL)-assisted delivery of topically applied drugs to varied targets in the skin has been an area of ongoing study and research. The objective of this study was to evaluate the efficacy and safety of fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser as an assisted drug delivery for enhancing topical hydroquinone (HQ) permeation into the skin of melasma patients.
Thirty female patients with bilateral melasma were randomly treated in a split-face controlled manner with a fractional Er:YAG laser followed by 4% HQ cream on one side and 4% HQ cream alone on the other side. All patients received six laser sessions with a 2-week interval. Facial halves were randomly assigned to receive treatment with fractional ablative 2940 nm Er:YAG laser (Fotona Xs Dynamis, Ljubljana, Slovenia) on one side, followed by application of topical 4% HQ cream. The other side was treated with 4% HQ cream only as a control. The laser settings were as follows: fluence 250–300 mJ, 30–40 μm ablation depth, handpiece PSO1, spot size 7 mm in diameter, short pulse duration mode, microthermal zone (MTZ) density level of 2–3, and frequency of 4–5 Hz. Two consecutive passes of nonoverlapping pulses were performed over melasma areas. The efficacy of treatments was determined through photographs, dermoscopic photomicrographs, and Melasma Area Severity Index (MASI) score, all performed at baseline and at 12 weeks of starting therapy. The patient’s level of satisfaction was also recorded.
Er:YAG laser + HQ showed significantly better results (P < 0.005) with regard to decrease in the degree of pigmentation as assessed on the four-point scale than HQ alone. There was a significant decrease in MASI scores on Er:YAG laser + HQ side vs. HQ side. At the end of treatment sessions, 73.4 and 40% of Er:YAG + HQ and HQ sides, respectively, were rated to have >50% improvement. The patients’ viewpoints on efficacy at the end of the study were similar to physician’s evaluation. Minor reversible side effects were observed on both sides.
To conclude, AFL-assisted delivery of HQ is a safe and effective method for the treatment of melasma.
Topical drug delivery system is one of the treatment strategies for melasma that has been a focus of attention in recent years. The present study shows promising results. A limitation of the present study is the lack of histological assessments of decreased pigmentation and vascular and mast cell changes. On the basis of these findings, fractional Er:YAG laser-assisted transcutaneous delivery of topical HQ is found to be an effective and safe treatment modality for melasma. AFL-assisted drug delivery may become a new important part of both medical and surgical dermatology. Nevertheless, cost will likely be a significant barrier to the widespread adoption of laser-assisted drug delivery techniques, and a cost-benefit analysis should be undertaken by physicians and their patients. As a final note, additional studies are needed to determine the optimal laser parameters in regard to achieve the ideal balance of fluence, treatment density, and drug concentration, ensuring the best efficacy and least incidence of adverse reactions.
Sharma S, Parsad D, Bhattacharjee R, Muthu SK. A prospective right–left comparative study to evaluate the efficacy and tolerability of combination of NB-UVB and topical bimatoprost 0.03% eye drops versus NB-UVB given alone in patients of vitiligo vulgaris. J Eur Acad Dermatol Venereol; 2018. doi: 10.1111/jdv.14882
Vitiligo is characterized by circumscribed depigmented macules and patches of skin. It is a multifactorial disorder due to genetic and environmental factors. Recent reports have highlighted darkening of iris, and eyelash and periocular hyperpigmentation induced by latanoprost (prostaglandin F2a analogue) used for the treatment of glaucoma. Extrapolating these findings in the treatment of vitiligo, we assessed the outcome of NB-UVB and topical bimatoprost 0.03% combination versus NB-UVB alone in a prospective right–left comparative study.
Twenty-five patients of slowly progressive vitiligo (up to five new lesions in last 1 month or up to 15 new lesions in last 3 months) were included, after a washout period of 2 weeks for those on previous treatment. Two paired patches of at least 2 × 2 cm in greatest dimension, on either side of the body served as target lesions and treated with 0.03% bimatoprost drops (2–3 drops) twice daily on left side and NB-UVB with standard initial dose of 280 mJ/cm2 on whole body including target lesions thrice a week. During treatment, repigmentation was assessed by serial photographs, investigator’s assessment score, percentage decrease in body surface area of target lesions by same observer using the Lund and Browder score, and patient’s assessment score − using the scale 1–10 at baseline and fortnightly for first 2 months and thereafter 4 weekly for 4 months. Patterns of repigmentation and colour match were assessed as per standard methods.
We found that response was better with combination treatment than NB-UVB alone throughout the study period and a statistically significant difference in mean percentage decreases in BSA between the two groups at 4, 8–16 and 24 weeks. More than 50% repigmentation was achieved in 10 (40%) patients with NB-UVB alone as compared to 13 (52%) patients with combination treatment, although this difference was not statistically significant.
Onset of repigmentation was earlier on combination side, although this difference was not statistically significant. Percentage improvement in repigmentation varied with the topography of the reference lesions, with truncal lesions responding best, followed by lower limbs, face, and upper limbs. Mean cumulative dose of NB-UVB at initial repigmentation (mJ/cm2) was the same for both groups. In addition, there was no statistically significant difference in color contrast between the two groups at 24 weeks. Moderate erythema persisting for more than 48 h after NB-UVB was seen in 3 (12%) patients. No side-effects were observed with bimatoprost.
The role of bimatoprost has not been studiedmuch in vitiligo. Although exact mechanism by which hyperpigmentation is induced by prostaglandins is elusive, different mechanisms proposed include influencing the responsiveness of melanocytes to neuronal stimuli, melanocyte proliferation; and direct or second messenger-mediated interaction with melanocytes via tyrosinase stimulation. The results of this study are not remarkable, yet 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 in the treatment of vitiligo.
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