Current best evidence in pigmentary dermatology

Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol 2023;88:395–403. Background Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. Objective To evaluate the efficacy and safety of ritlecitinib, an oral JAK3 (Janus kinase)/TEC (tyrosine kinase expressed in hepatocellular carcinoma) inhibitor, in patients with active nonsegmental vitiligo in a phase 2b trial (NCT03715829). Methods Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50, 100/50, 30, or 10 mg) or placebo for 24 weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50 mg daily in a 24-week extension period. The primary efficacy endpoint was percent change from baseline in facial-vitiligo area scoring index at week 24. Results A total of 364 patients were treated in the dose-ranging period. Significant differences from placebo in percent change from baseline in the facial-vitiligo area scoring index were observed for the ritlecitinib 50 mg groups with (−21.2 vs. 2.1; P < 0.001) or without (−18.5 vs. 2.1; P < 0.001) a loading dose and the ritlecitinib 30 mg group (−14.6 vs. 2.1; P = 0.01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period (n = 187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment. Limitations Patients with stable vitiligo only were excluded. Conclusions Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo. Comments Several JAK inhibitors, both topical and oral, have been recently approved for various dermatoses, including topical ruxolitinib approved for vitiligo. However, these drugs are associated with a number of side effects that are more common with pan-JAK inhibitors. In this study, oral ritlecitinib 50 mg was found to be an effective therapy for active non-segmental vitiligo in a large cohort. As ritlecitinib selectively inhibits JAK3, it has a better safety profile as compared to other JAK inhibitors like tofacitinib and ruxolitinib that were shown to be effective in vitiligo. Oral therapy may be more convenient for patients with extensive diseases where topical treatment may not be feasible. Further studies can be done, either alone or in combination, to validate the results of this study as well as to determine the time to relapse after discontinuation of ritlecitinb. Pazyar N, Hatami M, Yaghoobi R, et al. The efficacy of adding topical 5-fluorouracil to micro-needling in the treatment of vitiligo: a randomized controlled trial. J Cosmet Dermatol 2023;22:1513–20. Background and aim Vitiligo is an autoimmune skin disorder characterized by circumscribed depigmented macules and patches produced by the loss of functional melanocytes. Although there is no definitive treatment for vitiligo, numerous treatment options have been linked to somewhat satisfactory outcomes. The goal of this study was to compare the efficacy of micro-needling combined with topical 5-fluorouracil (5-FU) ointment versus topical tacrolimus ointment in treating vitiligo patches. Patients and methods This study included 19 participants, each of whom received both treatments on two randomly selected vitiligo patches of approximately the same size and location. On one patch, a combination of weekly micro-needling and topical application of 5-FU solution was used every other day, while on the other, 0.1% tacrolimus topical ointment was applied twice daily. The G-score was used to compare treatment outcomes after 3 months. Results The median duration of the disease in the study cohort was 7 years. Six patients (32%) in the micro-needling plus topical 5-FU treated group showed a moderate to excellent response, indicating a significant improvement between both treatments (P-value = 0.019). In contrast, all other patches treated with topical tacrolimus showed poor improvement. Lower extremity and trunk responded more to treatment with micro-needling plus topical 5-FU than upper extremity and acral areas. Moreover, none of those who have had the disease for more than 10 years had responded to treatment. Mild erythema, pinpoint bleeding, and irritation were detected only in the micro-needling treated group. Conclusion The current study found that using micro-needling in conjunction with 5-FU could repigment vitiligo patients more efficiently than tacrolimus monotherapy. Despite showing moderate to excellent improvement in patches treated with micro-needling and 5-FU, this well-tolerated office-based modality still requires additional research. Comments In this study, two symmetrical patches were treated with topical 0.1% tacrolimus twice daily in one group and micro-needling followed by 5-FU (50 mg/mL) in another group. Hyperpigmentation as side effect of 5-fluorouracil (FU) has previously been utilized in combination with other modalities for treatment of vitiligo. This randomized control trial has shown combination of micro-needling and topical 5-FU to be more effective than topical tacrolimus in stable vitiligo at the end of 3 months. While none of the patches treated with topical tacrolimus responded, micro-needling and the 5-FU combination showed a moderate to excellent response. Although associated with a few adverse effects such as mild erythema, pin point bleeding, and irritation, no major adverse effect was seen with 5-FU. The results of the study are encouraging, and further studies can be done to evaluate the effectiveness of 5-FU in the treatment of vitiligo. Similarly, micro-needling can also be combined with other topicals like tacrolimus to enhance penetration and effect. Gauthier Y, Lepreux S, Cario-Andre M, et al. Varicella-zoster virus in actively spreading segmental vitiligo skin: pathological, immunochemical, and ultrastructural findings (a first and preliminary study). Pigment Cell Melanoma Res 2023;36:78–85. Segmental vitiligo (SV) is a unilateral subtype of vitiligo that is clinically characterized by cutaneous depigmentation and histologically by melanocyte loss from the epidermis and hair follicle reservoirs. To date, its pathogenesis remains a mystery. In many cases, this skin depigmentation shares several clinical features and dysfunctions with herpes zoster (HZ). So, for the first time, the authors investigated whether any nucleus and cell fusion associated with a positive immunolabelling of varicella-zoster virus (VZV) and VZV mature virions could be found in SV skin samples as in herpes zoster (HZ). A total of 40 SV samples were used for histological and immunochemical studies. Control samples were obtained from three HZ, and 10 generalized vitiligo lesions. Three recent SV and one HZ were recruited as controls for ultrastructural study. Here, we report that nuclear fusion in epidermal cells was statistically associated with recent SV (P < 0.001), whereas syncytia formation was associated with long-lasting SV (P = 0.001). A positive detection of VZV antigen was statistically associated in the epidermis with recent SV and in the dermis with long-lasting SV (P = 0.001). Finally, the discovery of mature virions in 3/3 recent SV samples provides additional arguments for our viral hypothesis. Comments The pathogenesis of segmental vitiligo (SV) is still unknown, with several conflicting theories such as mosaicism and the neural hypothesis. This preliminary investigation while comparing histopathological and ultrastructural features of SV to that of herpes zoster and generalized vitiligo found possible role of varicella zoster virus (VZV) as etiology of SV. Nuclear fusion of epidermal cells was seen on histopathology in recent SV, which was confirmed by the presence of VZV antigens in the epidermis and in long-lasting SV, syncytia formation and VZV antigens in dermis were seen on histological and ultrastructural examination, respectively. Although, data are preliminary, further studies can be done to establish the exact role of VZV in causation of SV. Case reports of repigmentation in SV with valacyclovir opens the door for future trials of anti-VZV drugs in treatment of SV. The development of a medicinal therapy will obviate the need for surgical therapy, which is currently treatment of choice for SV. AboAlsoud ES, Eldahshan RM, AbouKhodair Mohammed H, Elsaie ML. Safety and efficacy of topical metformin 30% cream versus triple combination cream (Kligman's formula) in treating melasma: A randomized controlled study. J Cosmet Dermatol 2022;21:2508–15. Background Melasma is an acquired, common pigmentary condition that mostly presents as pigmented macules on the face. Triple combination creams (TCC), commonly known as Kligman's formula, have been regarded as the mainstay of treatment for years. Topical metformin was recently studied for its melanopenic effects and potential use in melasma. Aim of the work This study aimed to evaluate the efficacy and safety of using 30% metformin cream to that of triple combination creams (Kligman's formula) in treating melasma. Patients and methods About 40 patients of melasma were recruited for this controlled randomized trial and were divided into two groups. Group 1 (n = 20) subjects received 30% metformin cream whereas group 2 (n = 20) were treated with TCC for 8 consecutive weeks. Pigmentation severity and improvements were assessed using the melasma area severity index (MASI) at baseline and after 8 weeks of using treatment. Results MASI score decreased dramatically from 12.18 ± 9.33 before treatment to 5.59 ± 4.61 at Week 8 with a mean decrease percentage of 55.97 ± 16.77 for group 1 (P = 0.001) and from 16.05 ± 8.73 to 7.54 ± 5.77 with a mean decrease percentage of 56.50 ± 19.44 for group 2 (P = 0.001). No significant difference was reported between the two treatment modalities regarding the reduction in melasma throughout the study period (P = 0.968). Conclusion Metformin cream is a safe, potential effective treatment for melasma, which needs to be verified by long-term large scale studies in diffident populations. Comments Triple combination is known to be single conventional most-effective treatment modality for melasma, a difficult to treat, chronic, and recurrent dermatosis. However, it is commonly associated with serious adverse effect, exogenous ochronosis, especially on long term, unguided use. This necessitates the search for an effective as well as safe treatment option. Topical metformin, recently shown to have melanopenic effect, so can have therapeutic effect in melasma. This randomized controlled trial has shown metformin to be effective in melasma consistent with the findings of previous trials. As histological and immunohistochemical correlation of results was not done in this study, further trials can be done in the future to investigate the effect of metformin on melasma. Afify AA, Zuelfakkar NM, and Eshafi MA. Fractional CO2 laser, platelet rich plasma and narrow band ultraviolet B in the treatment of vitiligo (a randomized clinical trial). Lasers Med Sci 2021;36:1479–86. Vitiligo is a chronic, acquired disease. Various therapeutic strategies are available, but with varying degrees of success. Fractional CO2 laser is claimed to be effective in the treatment of refractory non-segmental vitiligo. Platelet-rich plasma may help in stimulation and proliferation of melanocytes and repigmentation within vitiliginous patches. Our aim was to evaluate and compare the efficacy and safety of fractional CO2 laser, PRP, and NB-UVB either alone or in combination in the treatment of vitiligo. This self-controlled randomized clinical trial included 20 patients with at least 6 patches of vitiligo (VIDA scores 1 and 0). Each patch was randomly assigned to receive either fractional CO2 laser, PRP, combined fractional CO2 with PRP, combined fractional CO2 with NB-UVB, combined fractional CO2 with PRP and NB-UVB, or left as a control. There was a statistically significant improvement in all treatment groups when comparing the surface area of vitiligo patches before and after treatment. However, on comparing the percentage of reduction in surface area in different treatment groups, there was no statistically significant difference (P = 0.122). Fr:CO2 laser and PRP may be adjuvant therapeutic options to NB-UVB, especially in the treatment of refractory cases of non-segmental vitiligo. Comments Various therapies are available for the treatment of vitiligo; however, no single treatment is fully effective, especially for non-segmental vitiligo. This study comparing fractional CO2 laser, platelet-rich plasma (PRP), and narrow-band UVB alone or in combination showed that all of them lead to a significant reduction in the size of vitiligo patches as compared to the baseline surface area. In addition, there was no significant difference between the different treatment modalities. Fractional CO2 lasers can be effective for vitiligo, and along with PRP, they may serve as an adjuvant treatment option for vitiligo patients. The method of assessment of vitiligo lesions by computer-aided grid assessment used in this study is a novel and quantitative outcome measurement of vitiligo. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.