Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Target area treatment ratio of varied lesions in the cultured pure melanocyte transplantation repigmentation of vitiligo: A retrospective study.

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).

Caffeic acid derivative WSY6 protects melanocytes from oxidative stress by reducing ROS production and MAPK activation.

Purpose: Vitiligo is a chronic depigmentation disease caused by a loss of functioning melanocytes and melanin from the epidermis. Oxidative stress-induced damage to melanocytes is key in the pathogenesis of vitiligo. WSY6 is a caffeic acid derivative synthesized from epigallocatechin-3-gallate (EGCG). This study is to investigate whether the new chemical WSY6 protected melanocytes from H2O2-induced cell damage and to elucidate the underlying molecular mechanism. Patients and methods: The present study compared the antioxidative potential of WSY6 with EGCG in hydrogen peroxide (H2O2)-treated PIG1 cells. Western blotting was used to study the protein expression of cyto-c, cleaved-caspase3, cleaved-caspase9, and the activation of MAPK family members, including p38, ERK1/2, JNK and their phosphorylation in melanocytes. ROS assay kit to detect intracellular reactive oxygen species production; CCK8 and lactate dehydrogenase leak assay to detect cytotoxicity. Results: EGCG and WSY6 ameliorated H2O2-induced oxidative stress damage in PIG1 cells in a does-dependent manner, while WSY6 was much more effective. WSY6 reduced cellular ROS production, cytochrome c release, downregulated caspase-3 and caspase-9 activation. MAPK pathway signaling including phosphorylated p38, ERK and JNK were observed under oxidative stress and can be much protected by pre-treatment of WSY6. Conclusion: These results indicated that WSY6 could be a more powerful antioxidant than EGCG and protect melanocytes against oxidative cytotoxicity.

Results and Follow-Up of a Sequential Q-Switched Laser Therapy for Nevus of Ota in Infants.

Background and Aim: There is a dearth of scholarly investigation pertaining to the effectiveness and safety of laser therapy for nevus of Ota manifestation in infants. The objective of this study is to examine the efficacy and safety of administering laser therapy at an early stage to treat nevus of Ota in infants. Methods: A total of 102 infants below the age of one who had nevus of Ota were treated at the Laser Center at Hangzhou Third People's Hospital. The treatment approach involved a combination of the Q-switched laser (with a wavelength of 755 nm) and the Q-switched laser (with a wavelength of 1064 nm). The treatment sessions were conducted at six-month intervals. Prior to and after each session, photographs and relevant parameters were documented, including any skin reactions. Subsequent follow-up was conducted through phone calls, WeChat, and text messages, and the parents/guardians of the infants completed a general questionnaire as well as Conner's Abbreviated Symptom Questionnaire. Results: Laser therapy exhibited significant efficacy in the treatment of nevus of Ota in infants. Success rates reached 88.7% after four sessions and 99.3% after seven sessions. No instances of serious adverse reactions, except for pain, were reported. Among the 47 infants subject to follow-up, 14 experienced a recurrence, resulting in a recurrence rate of 29.8%. Factors contributing to these recurrences included lesion size, subtypes, exposure to the sun, and location. Subsequent laser treatments, typically involving two to three additional sessions, proved effective in mitigating recurrences. Notably, none of the infants exhibited any signs of fear, anxiety, or other psychological abnormalities following laser therapy, and the overall satisfaction rate was markedly high. Conclusion: Commencing laser therapy promptly for nevus of Ota in infants is recommended. This early intervention significantly contributes to the overall well-being of infants, addressing both physical and psychological aspects.

Comparative outcomes of autologous cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in piebaldism patients: A retrospective study.

PURPOSE: To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of piebaldism. PATIENTS AND METHODS: A retrospective study was conducted on 30 anatomically based lesions from nine piebaldism patients who underwent either CMT (n = 7) or NCES (n = 23) between 2018 and 2020. The extent of repigmentation and colour matching was evaluated in all recipient sites using a digital imaging analysis system. In addition, adverse effects have also been assessed by follow-up results. RESULTS: More than 75% repigmentation was achieved in 100% (7/7) and 60.9% (14/23) of the 30 lesions with the CMT and NCES, respectively. There were significant differences between the two methods in terms of repigmentation. The majority of patients had colour mismatches, and there was no discernible difference between the two surgical techniques. Adverse reactions rarely occurred. CONCLUSION: The present study suggested that autologous CMT may provide better repigmentation in piebaldism patients than NCES with no significant side effects.

EGR1 Mediated Reduction of Fibroblast Secreted-TGF-ß1 Exacerbated CD8+ T Cell Inflammation and Migration in Vitiligo.

Vitiligo is a T cell-mediated depigment skin disease caused by the complex interplay between melanocyte dysfunction, environmental stimulation, and dysregulated immune signals. Transforming growth factor-ß1 (TGF-ß1), which typically derives from regulatory T cells, has long been identified at low levels in the peripheral system of vitiligo patients. Here, through RNA-sequencing and transcription factor enrichment, we revealed that in response to CD8+ T cell-secreted interferon-gamma (IFN-γ), stromal fibroblast downregulates early growth response 1 (EGR1) activity, leading to TGF-ß1 deficiency. The defective immune regulation loop further exacerbated local CD8+ T cell inflammation and promoted inflammatory cell migration in vitiligo. Thus, fibroblast-derived TGF-ß1 plays an important stromal signal in vitiligo pathogenesis.

Pathogenic Th2 Cytokine Profile Skewing by IFN-γ-Responding Vitiligo Fibroblasts via CCL2/CCL8.

PURPOSE: Vitiligo is a T cell-mediated skin depigmentation disease. Though treatments arresting disease progression and inducing repigmentation are available, the efficacy of these options is often limited and poorly sustained. How stromal signals contribute to the interferon-γ-dominant skin niches is unclear. This study aims to determine how fibroblasts participate in the IFN-γ-dominant vitiligo niche. PATIENTS AND METHODS: Mouse vitiligo models were established. Fibroblasts from control and vitiligo mice were extracted for RNA sequencing. In vitro IFN-γ stimulation was performed to verify the JAK-STAT pathway by qPCR and Western blot. T cell polarization with chemokines was measured by flow cytometry. Protein levels in tissues were also examined by IHC. RESULTS: The vitiligo mouse model recapitulates the human CD8-IFN-γ pathway. RNA sequencing revealed elevated chemokine CCL2 and CCL8 in vitiligo fibroblast, which may be regulated by the JAK-STAT signaling. Such phenomenon is verified by JAK inhibitor peficitinib in vitro. Moreover, CCL2 addition into the naïve T polarization system promoted type 2 cytokines secretion, which represents a hallmark of vitiligo lesions. CONCLUSION: Dermal fibroblasts, a principal constituent of skin structure, respond to IFN-γ by skewing T cells towards a type 2 cytokine profile via CCL2 and CCL8, which can be abrogated by JAK inhibitor peficitinib.

A Typical but Rare Case of Solitary Tinea Auricularis.

Tinea auricularis is a rare superficial fungal infection, which is easily ignored in clinic due to its atypical clinical symptoms or being accompanied with tinea capitis. In this study, a case of annular erythema with scales around the ear canal orifice was reported. After fungal culture and identification, the patient was diagnosed with Trichophyton rubrum infection, and was cured after 3 weeks of topical use of clotrimazole cream.

Impacts of exposure to topical calcineurin inhibitors on metabolism in vitiligo infants.

BACKGROUND: Tacrolimus ointment is a recently developed topical immunomodulator that has been approved for use in patients with vitiligo older than 2 years. Concern regarding potential systemic toxic effects has limited treatment options for children younger than 2 years. We wanted to determine whether topical tacrolimus therapy is safe and effective in patients with vitiligo younger than 2 years. METHODS: The present 6-month clinical trial was conducted to evaluate the efficacy and safety of 0.03% tacrolimus in the treatment of vitiligo in children under 2 years of age. Meanwhile, serum and urine samples were collected, and liquid chromatography-mass spectrometry was performed to generate the serum and urine metabolic profile data of patients and healthy controls. RESULTS: The overall response rate at the sixth month, which was defined by the degree of re-pigmentation, was 100%. As revealed by blood monitoring and metabolite detection 6 months later, there was no difference between the treatment group and the control group. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. CONCLUSIONS: Tacrolimus ointment appears to be effective and safe in the treatment of vitiligo in children younger than 2 year. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR 2100045920. IMPACT: We first reported the efficacy and safety of topical application of 0.03% tacrolimus ointment in infants with vitiligo characterized by the metabolites. There is no evidence that long-term topical application of 0.03% tacrolimus ointment will cause metabolite or other physical changes in the body. This study provide evidence for the TCI treatment of infants with vitiligo.

Tinea of vellus hair: shining under the Wood's lamp.

We herein reported a simple and cheap method to diagnose the tinea of vellus hair, which is long-neglected and always wrongly treated.

Repigmentation in two patients with vitiligo on AcEGCG 0.5% cream.

Per-acetylated epigallocatechin-3-gallate (AcEGCG), a fully acetylated derivative of EGCG, a more potent agent for protection of melanocytes from oxidative damage. We present two patients with vitiligo treated with AcEGCG 0.5% cream, who demonstrated skin repigmentation and control of depigmentation progression.

Narrowband Ultraviolet B Combined with Topical Simvastatin Solution in the Treatment of Vitiligo: A Case Report.

Background: Phototherapy is one of the treatments for vitiligo. To be specific, the combination of narrowband ultraviolet B (NB-UVB) with topical preparations has currently become the most common therapeutic modality. Moreover, the research on new topical drug has been a hot issue in the field of vitiligo. Objective: At present, simvastatin has been considered as a potential therapeutic agent for the treatment of vitiligo. To the best of our knowledge, this is the first case report concerning the successful application of NB-UVB combined with topical simvastatin in the treatment of vitiligo. Methods: In this article, a clinical case report was presented, where the patient was not responsive to NB-UVB but was markedly responsive to the treatment of UVB combined with topical simvastatin. Results: A 34-year-old Chinese female patient with vitiligo was cured by NB-UVB combined with topical simvastatin solution. Conclusions: NB-UVB combined with topical simvastatin may be a potential treatment against vitiligo. This research was approved by the Medical Ethics Committee of Third People's Hospital of Hangzhou.

Altered circulating memory T cells in vitiligo cases followed NB-UVB therapy.

BACKGROUND: Vitiligo represents a commonly diagnosed autoimmune disease caused by the depletion of epidermal melanocytes. Many subsets of T cells contribute to vitiligo pathogenesis, including resident and circulating memory T cells. OBJECTIVES: To analyze the amounts of CD4+ and CD8+ memory T-cell subsets in peripheral blood specimens from vitiligo patients and alterations caused by narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Circulating CD4+ and CD8+ central memory T (TCM ) and effector memory T (TEM ) cell frequencies in 33 patients with non-segmental vitiligo and 16 healthy donors were evaluated by flow cytometry. Related chemokine levels were also detected. RESULTS: Peripheral blood CD4+ TCM and CD8+ TCM counts were markedly reduced in vitiligo cases while they were higher in active vitiligo compared with stable vitiligo cases. Circulating CD8+ TCM frequency in vitiligo was closely related to disease duration. Interestingly, CD4+ TCM and CD8+ TCM frequencies, alongside CXCL9 and CXCL10 amounts in peripheral blood of patients with vitiligo, were significantly decreased after NB-UVB phototherapy. CONCLUSIONS: Decreased frequencies of circulating CD4+ TCM and CD8+ TCM by NB-UVB suggest a possible immunosuppressive effect of phototherapy. The chemokines CXCL9 and CXCL10 are the bridge between circulating and skin resident memory T cells. NB-UVB blocks the homing of circulating memory T cells into vitiligo lesions by down-regulating CXCL9 and CXCL10. Targeting the above proteins could provide novel, durable treatment options to cure and prevent flares of this disease.

[Corrigendum] The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes.

Following the publication of the above article, an interested reader drew to the authors' attention that the Transwell cell migration assay data shown in Fig. 4A appeared to be partly overlapping with data presented for experiments performed under different experimental conditions in Figs. 4D and E. The authors independently examined the figure and realized that inadvertent errors had been made during the assembly of Fig. 4; furthermore, owing to the time that has elapsed since this paper was published, the authors no longer had access to the original data. Accordingly, to further verify the conclusions reported in the study, the authors repeated these experiments, and the results obtained were found to be consistent with the original findings. The new version of Fig. 4 is shown below. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 26: 57-65, 2010; DOI: 10.3892/ijmm_00000435].