|CURRENT BEST EVIDENCE
|Year : 2022 | Volume
| Issue : 2 | Page : 143-145
Current best evidence in pigmentary dermatology
Sheenam Sethi, Vishal Thakur
Department of Dermatology, Venereology, and Leprosy, Himalayan Institute of Medical Sciences, Dehradun, India
|Date of Submission||02-Feb-2022|
|Date of Decision||14-Feb-2022|
|Date of Acceptance||14-Mar-2022|
|Date of Web Publication||12-Aug-2022|
Dr. Vishal Thakur
Department of Dermatology, Venereology, and Leprosy, Himalayan Institute of Medical Sciences, Dehradun 248140
Source of Support: None, Conflict of Interest: None
Keywords: Fluoxetine, JAK inhibitors, melasma, narrowband UVB, tranexamic acid, vitiligo
|How to cite this article:|
Sethi S, Thakur V. Current best evidence in pigmentary dermatology. Pigment Int 2022;9:143-5
| REPIGMENTATION IN VITILIGO USING JANUS KINASE (JAK) INHIBITORS|| |
- Phan K, Phan S, Shumack S, Gupta M. Repigmentation in vitiligo using Janus kinase (JAK) inhibitors with phototherapy: systematic review and meta-analysis. J Dermatol Treat 2020;2:1-5.
Vitiligo is an acquired pigmentary disorder associated with progressive loss of melanocytes leading to depigmented patches over the skin, mucosae, or both. Vitiligo has a significant psychosocial impact on the quality of life of patients. Treatment of vitiligo is often challenging despite the availability of many treatment modalities and response is variable or incomplete. Of late, the use of Janus kinase (JAK 1/3) inhibitors has shown promising results in the treatment of vitiligo.
This systematic review and meta-analysis have evaluated the response to JAK inhibitors, including tofacitinib and ruxolitinib in vitiligo patients. A total of 9 articles with data from 45 cases were included. Univariate analysis was performed according to components: oral versus topical JAK inhibitor therapy, no phototherapy versus phototherapy. Good response as defined as repigmentation >50% was achieved in 57.8%. Partial response as defined as some repigmentation <50% was observed in 22.2% and none or minimal response in 20% of patients. Among the sites involved, facial vitiligo had an eminent good response rate (70%). Simultaneous phototherapy was profoundly associated with prominent response (P < 0.001) and good facial response (P < 0.01). There was indistinguishability in good response rates upon the use of topical versus oral JAK inhibitors. Limitations of the study include small data and low-quality evidence (case reports). There is evident selection bias and publication bias, given that only positive results must have been published.
The results of this systematic review and meta-analysis show encouraging results of JAK inhibitors in vitiligo, especially when used in combination with phototherapy. Combined treatment with ultraviolet B (UVB) therapy helps repigmentation by causing immunosuppression and stimulation of melanocytes, thus improving the efficacy of JAK inhibitors in vitiligo. The response of JAK inhibitors whether topical or oral was comparable, thus implying that the topical route can be used with equal efficacy when minimizing the risk of serious side effects such as herpes zoster or reactivation of tuberculosis. However, the results are mostly from case reports or case series and for determining the effectiveness of JAK inhibitors, large randomized trials are required with longer follow-up.
| TOPICAL CORTICOSTEROIDS AND NB-UVB IN ACTIVE AND LIMITED VITILIGO|| |
- KS, Batchelor JM, Akram P, et al. Randomized controlled trial of topical corticosteroids and home-based NB-UVB for active and limited vitiligo: results of the HI-Light vitiligo trial. Br J Dermatol 2021;184:828-39.
Vitiligo is a common pigmentary disorder resulting in deprivation of skin pigmentation owing to autoimmune melanocyte destruction. Topical corticosteroids (TCSs), topical calcineurin inhibitors, and narrowband (NB) UVB are commonly used therapies for vitiligo.
This three-arm (1:1:1 = TCS plus dummy NB-UVB: vehicle ointment with NB-UVB: TCS mometasone furoate ointment with NB-UVB), pragmatic, placebo-controlled randomized trial was performed across 16 UK hospitals for 21 months (treatment for 9 months, 12 months of follow-up) from July 2015 to September 2017 (n = 517). This study aimed to compare efficacy and well-being of home-based interventions for the treatment of limited and active vitiligo, differentiating firstly, handheld NB-UVB versus potent TCS and secondly, an aggregation of handheld NB-UVB plus potent TCS versus potent TCS alone. Patients with nonsegmental vitiligo limited to approximately 10% or less Body surface area (BSA) and at least 1 patch that had been active in the last 12 months were enrolled in the study. Three patches from three anatomical regions (hands and feet, head and neck, and rest of body) were chosen by participants with one being selected as the target patch for primary outcome assessment. All participants received an NB-UVB light unit (active or dummy; used on alternate days) and either a TCS (mometasone furoate 0.1% ointment) or vehicle (placebo), applied daily on alternate weeks. Patients attended clinics on 2 consecutive days at baseline and then, at 3, 6, and 9 months to assess outcomes. Follow-up thereafter was by 3-monthly questionnaires. Outcome measures included the vitiligo noticeability scale with success as “a lot less noticeable” or “no longer noticeable,” percentage repigmentation, improvement in quality of life, maintenance of treatment response, and safety profile. This study also assessed whether treatment response was maintained once interventions were stopped. Combination treatment with TCS and NB-UVB (treatment success in 27%) was superior to TCS alone (17%) and NB-UVB alone (22%). Treatment success at 9 months was lower for patches on hands and feet than other regions. Most patients had onset of eminent response by 3 months. During the follow-up phase, >40% of patients reported vanishing treatment response by 21 months, across all groups. Both vitiligo-specific quality of life and generic scores were alike at follow-up across groups. In total, 25% of patients reported treatment-related adverse events.
NB-UVB is usually available as whole-body therapy and regular hospital visits are required. Literature for the use of handheld NB-UVB in combination with TCSs is very limited. This study concluded that combination treatment was superior to TCS alone, but NB-UVB alone was not superior to TCS. This trial has good external validity, as people with all skin types and of all ethnicities were included. Safety data layout suggests that mometasone furoate can be used safely intermittently “1 week on, 1 week off” for approximately 9 months, as carried out in this study. In conclusion, combination therapy can lead to improved treatment response compared with either treatment alone.
| EFFECTS OF LONG-TERM NARROWBAND UVB PHOTOTHERAPY ON THE RISK OF CARDIOVASCULAR AND CEREBROVASCULAR EVENTS IN VITILIGO PATIENTS|| |
- Bae JM, Kim YS, Choo EH, et al. Both cardiovascular and cerebrovascular events are decreased following long-term narrowband ultraviolet B phototherapy in patients with vitiligo: a propensity score matching analysis. J Eur Acad Dermatol Venereol 2021;35:222-9.
NB-UVB phototherapy that utilizes a peak wavelength of 311 nm is the mainstay of treatment for vitiligo for decades. It is given two to three times per week for various months or years to attain noticeable repigmentation, thus, causing major concerns due to long-term UV exposure. Dermatologic effects of NB-UVB are fully acknowledged but effects on internal health have not been fully looked into.
This countrywide population-based retrospective cohort study (2007–2017) analyzed the effects of long-term UV exposure on cerebrovascular and cardiovascular events in vitiligo patients. All patients were sorted into two groups by the number of phototherapy treatment sessions underwent – <3 (no-phototherapy group, n = 9687) and ≥100 (phototherapy group, n = 3229). The gross incidence rates of cerebrovascular and cardiovascular events were 60.0 and 95.6 per 10,000 person-years in the phototherapy and no-phototherapy groups, respectively. The phototherapy group showed a lower risk of ischemic heart disease [hazard ratio (HR) = 0.7] and myocardial infarction (HR = 0.508) than the no-phototherapy group. The phototherapy group also showed a lower risk of cerebral infarction (HR = 0.581) and cerebral hemorrhage (HR = 0.955) than the no-phototherapy group. Findings were concordant in the subgroups according to sex (male and female) or age (40–59 and ≥60 years). Possible advantages and disadvantages of long-term phototherapy can differ between ethnicities, such as the risk of skin cancer, thus, necessitating further research.
Systemic inflammation in diseases such as psoriasis leads to increased cardiovascular events and studies have shown the beneficial effects of systemic anti-inflammatory drugs in decreasing the risk of these events. However, systemic effects of phototherapy have been investigated in only a few studies which showed that long-term NB-UVB phototherapy reduces blood pressure by releasing nitric oxide from the skin and also decreasing inflammatory markers. NB-UVB has also been shown to inhibit the progression of atherosclerosis by modulating proatherogenic T-cell response. Furthermore, the role of systemic inflammation in the pathogenesis of vitiligo is also implicated. Thus, NB-UVB by decreasing the systemic inflammatory markers may help decrease the cardiovascular events and disease per se. However, further research exploring the beneficial effects of the NB-UVB cardiovascular system is warranted.
| LASER-ASSISTED DELIVERY OF TRANEXAMIC ACID FOR MELASMA|| |
- Wang JV, Christman MP, Feng H, Ferzli G, Jeon H, Geronemus RG. Laser-assisted delivery of tranexamic acid for melasma: pilot study using a novel 1927 nm fractional thulium fiber laser. J Cosmet Dermatol 2021;20:105-9.
Melasma is qualified as a chronic and reverting occurrence of gray-to-brown blotches on sun-exposed areas of the face and neck. Melasma can be associated with huge psychosocial stress. Available treatment alternatives offer only transient or partial improvement. This prospective pilot study enrolling 10 patients of melasma was carried out to evaluate the practicability of a combination of low-energy, low-density 1927 nm fractional thulium fiber laser with topical tranexamic acid. Seven out of 10 subjects completed the study and all were female. Each received 5 full-face treatments with laser at 21(+7)-day intervals followed immediately by application of tranexamic acid. The treatment area was coated with 1 cc approximately. Subjects were also advised to apply it twice daily for 7 days. At baseline, melasma area and severity score (MASI) for all subjects was 10.6. Maximum improvement in MASI scores was reported at a 90-day follow-up. The mean improvement of the melasma quality of life scale score was 9.6 at 30-day follow-up. Thus, this combination can result in marked clinical improvement and betterment of the quality of life associated with melasma.
UV light increases the activity of plasmin in keratinocytes, increasing melanocytic-stimulating mediators, which has led to research of tranexamic acid for treatment of melasma as it possesses antiplasmin properties. The uptake of topical medications can be increased by the use of laser-assisted drug delivery (LADD). With LADD, there is disruption of the stratum corneum creating tiny microchannels, microscopic treatment zones. Physical properties of topical medication (lipophilic or lipophobic/pH/vehicle type) also impact drug delivery in addition to laser settings. A study with a larger sample size is required for further confirmation of the utility of this combination.
| SEROTONIN REUPTAKE INHIBITION – A NEW ANTIGRAYING STRATEGY|| |
- Cheret J, Gherardinin J, Bertolini M, Paus R. Fluoxetine promotes human hair follicle pigmentation ex vivo: serotonin reuptake inhibition as a new anti greying strategy? British J Dermatol 2020;182:1492-4.
Fluoxetine, a commonly prescribed anti-depressant, is reported to induce epidermal hyperpigmentation after systemic intake. Selective serotonin reuptake inhibitor also stimulates the production of melaninin murine hair follicles (HFs) and cultured human epidermal melanocytes in vitro. This pilot study explored the direct impact of fluoxetine on human HF pigmentation. Pigmented, full-length scalp HFs in anagen VI were treated for 48 hours with 100 nmol/L and 1 μmol/L fluoxetine in serum-free supplemented William E medium. Quantitative Masson–Fontana histomorphometry showed that melanin production was significantly increased by fluoxetine in HF pigmentary unit of already maximally pigmented anagen VI HFs ex vivo. Strikingly, fluoxetine also induced significant restimulation of intrafollicular melanin production after 6 days of HF organ culture in a small number of white HFs isolated from 5 female donors with >50% canities. This preliminary evidence proposes that fluoxetine can reactivate at least some canities affected HFs to produce melanin. The expression of α-MSH, a key neuroendocrine stimulator of human HF pigmentation, can be modulated by fluoxetine.
The current pilot data are prelusive and require thorough production in additional HFs from more individuals. The clinical key dispute is to evaluate whether the observed ex vivo effects of fluoxetine translate to the in vivo situation (ideally after topical application).
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Conflicts of interest
There are no conflicts of interest.