Bridging Molecular Mechanism and Clinical Practice in Vitiligo Treatment: An Updated Review.

BACKGROUND: Treatment of vitiligo seeks to achieve three goals: cessation of disease progression, regeneration of pigmentation, and prevention of recurrence. SUMMARY: Number of nonsurgical interventions are available that suppress the autoimmune response and regenerate the melanocytes from the reservoir: phototherapy including psoralen and ultraviolet A, narrowband ultraviolet B, and 308-nm excimer and 311-nm Titanium:Sapphire lasers; topical agents including topical calcineurin inhibitors, topical corticosteroids, and topical 5-fluorouracil; and systemic agents including corticosteorids, mycophenolate mofetil, cyclosporine, methotrexate, minocycline, afamelanotide, and antioxidants. In recent years, a great advance has been made in the understanding of pathogenesis of vitiligo, and JAK inhibitors are being investigated as a new treatment. Minimally invasive procedures such as fractional lasers or microneedling can help achieve the optimal treatment outcome when used properly. KEY MESSAGES: Our review describes various treatment modalities for vitiligo based on their molecular mechanism of action. Bridging the gap between molecular mechanisms and therapeutic options would be a valuable reference for physicians in clinical practice.

Factors influencing the quality of life in children with atopic dermatitis in Korea: A multicenter cross-sectional study.

Background: There is a lack of studies about which factors affect the quality of life (QoL) in children with atopic dermatitis (AD), although it is well known that AD has considerably negative effects on their QoL. Objective: This study aimed to measure the QoL in children with AD and identify the factors that affect their QoL. Methods: A questionnaire derived from the Children's Dermatology Life Quality Index (CDLQI) was used to measure QoL. Family history, allergic comorbidities, exacerbation-related factors, time of exacerbation, and previous and current treatment were also evaluated. The total immunoglobulin E (IgE) level and specific IgE sensitization were determined by the multiple allergen simultaneous test, allergy test, or skin-prick test. AD severity was categorized into mild, moderate, and severe based on treatments. Results: In total, 254 children (46.4 months, 53% boys) from seven hospitals completed the survey. The mean CDLQI score was 7.2 ± 5.5 (total score range of 0-30). The respondents were divided into three groups according to their QoL score distribution, with 0 - 4 points (n = 84), 5 - 9 points (n = 90), and ≥10 points (n = 80) representing good, fair, and poor QoL, respectively. The more severe AD showed the higher CDLQI score significantly (p = 0.001). Compared with other groups, children with poor QoL were more sensitized to inhalant allergens (odds ratio [OR] 1.29 [95% confidence interval {CI}], 1.03 - 1.62) and had more exacerbating factors (OR 1.26 [95% CI, 1.04 - 1.54]), which included inhalation allergen-related exacerbating factors (OR 2.54 [95% CI, 1.23 - 5.23), even after adjusting for age, total IgE, body mass index, severity, and use of moisturizer. The concordance between animal sensitization and an exacerbating factor, including dog and cat, was fair, with 0.39 κ and 0.85 accuracy. Conclusion: This study showed that impaired QoL in children with AD is associated with inhalant allergen sensitization and inhalant allergen-related exacerbation factors. Especially, dog and cat sensitization was a significant exacerbating factor. The inhalation-related exacerbation factors, including animal allergens, might be addressed to improve AD management in children.

Has the core outcome (domain) set for vitiligo been implemented? An updated systematic review on outcomes and outcome measures in vitiligo randomized clinical trials.

BACKGROUND: In 2015, a major achievement in vitiligo research was the development of an internationally agreed upon core outcome domain set for randomized clinical trials (RCTs). Three outcomes were identified as being essential: repigmentation, side-effects/harms and maintenance of gained repigmentation. Four items were further recommended for inclusion. The following recommendations then followed: repigmentation should be assessed by measuring the percentage of repigmentation in quartiles (0-25%, 26-50%, 51-79%, 80-100%) and cosmetic acceptability of the results should be assessed using the Vitiligo Noticeability Scale. OBJECTIVES: The primary objective of this study was to assess uptake of the core outcome domain set for RCTs in vitiligo. Secondary objectives were to update the systematic review on outcomes reported in vitiligo RCTs, and to assess whether repigmentation and cosmetic acceptability of the results were measured using the above-mentioned recommended scales. METHODS: We searched PubMed, Cochrane Library (CENTRAL and Systematic Reviews) and ClinicalTrials.gov for vitiligo RCTs between November 2009 and March 2021. Screening and data extraction were independently performed on title and summary by two researchers. All outcomes and outcome measures reported in eligible RCTs were retrieved and collated. RESULTS: In total, 174 RCTs were identified: 62 were published between 2009 and 2015, and 112 were published between 2016 and 2021.Thirty-eight different outcomes were reported. Repigmentation was the primary outcome in 89% of trials (150 of 169). Forty-nine different tools were used to measure repigmentation. Side-effects and harms were reported in 78% of trials (136 of 174). Maintenance of gained repigmentation was reported in only 11% of trials (20 of 174) and duration of follow-up varied greatly from 1 to 14 months. Cosmetic acceptability of the results and cessation of disease activity were assessed in only 2% of trials (four of 174). Quality of life of patients with vitiligo was assessed in 13% of trials (22 of 174). Finally, only 11 of 112 RCTs (10%) published between 2016 and 2021 reported all three essential core outcome domains (repigmentation, side-effects and maintenance of gained repigmentation) and none of the trials reported both essential and recommended core outcome domains. CONCLUSIONS: Efforts are still needed to close the gap between set recommendations and RCT outcome reporting.

Reliability and agreement testing of a new automated measurement method to determine facial vitiligo extent using standardized ultraviolet images and a dedicated algorithm.

BACKGROUND: Facial repigmentation is the primary outcome measure for most vitiligo trials. The Facial Vitiligo Area Scoring Index (F-VASI) score is often chosen as the primary outcome measure to assess the efficacy of treatments for facial vitiligo. Although useful, this scoring system remains subjective and has several limitations. OBJECTIVES: To assess the agreement and reliability of an algorithmic method to measure the percentage depigmentation of vitiligo on the face. METHODS: We developed a dedicated algorithm called Vitil-IA® to assess depigmentation on standardized facial ultraviolet (UV) pictures. We then conducted a cross-sectional study using the framework of the ERASE trial (NCT04843059) in 22 consecutive patients attending a tertiary care centre for vitiligo. Depigmentation was analysed before any treatment and, for 7 of them, after 3 and 6 months of narrowband UVB treatment combined with 16 mg methylprednisolone, both used twice weekly. Interoperator and interacquisition repeatability measures were assessed for the algorithm. The results of the algorithmic measurement were then compared with the F-VASI and the percentage of depigmented skin scores assessed by 13 raters, including 7 experts in the grading of vitiligo lesions. RESULTS: Thirty-one sets of pictures were analysed with the algorithmic method. Internal validation showed excellent reproducibility, with a variation of < 3%. The percentage of depigmentation assessed by the system showed high agreement with the percentage of depigmentation assessed by raters [mean error (ME) -11.94 and mean absolute error (MAE) 12.71 for the nonexpert group; ME 0.43 and MAE 5.57 for the expert group]. The intraclass correlation coefficient (ICC) for F-VASI was 0.45 [95% confidence interval (CI) 0.29-0.62] and 0.52 (95% CI 0.37-0.68) for nonexperts and experts, respectively. When the results were analysed separately for homogeneous and heterogeneous depigmentation, the ICC for homogeneous depigmentation was 0.47 (95% CI 0.31-0.77) and 0.85 (95% CI 0.72-0.94) for nonexperts and experts, respectively. When grading heterogeneous depigmentation, the ICC was 0.19 (95% CI 0.05-0.43) and 0.38 (95% CI 0.20-0.62) for nonexperts and experts, respectively. CONCLUSIONS: We demonstrated that the Vitil-IA algorithm provides a reliable assessment of facial involvement in vitiligo. The study underlines the limitations of the F-VASI score when performed by nonexperts for homogeneous vitiligo depigmentation, and in all raters when depigmentation is heterogeneous.

Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination.

BACKGROUND: Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited. OBJECTIVE: To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination. METHODS: This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared. RESULTS: A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status. LIMITATIONS: Possible selection bias and residual confounders. CONCLUSION: These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.

Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial.

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 hepatocelluar 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 mg, 100/50 mg, 30 mg, 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 Facial-Vitiligo Area Scoring Index were observed for the ritlecitinib 50 mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30 mg group (-14.6 vs 2.1; P = .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.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Development and validation of the fingertip unit for assessing Facial Vitiligo Area Scoring Index.

BACKGROUND: Facial involvement of vitiligo is an important factor in a patient's life and has often been evaluated separately from body surface area in clinical trials. However, no reliable tools to measure facial vitiligo specifically are available thus far. OBJECTIVE: To develop and validate a practical instrument for assessing facial vitiligo. METHODS: The ratios of a hand to a fingertip unit (FTU) of 98 healthy volunteers (age range, 2-69 years) were calculated to define the FTU. Facial Vitiligo Area Scoring Index was measured as the sum of all FTUs of each vitiligo lesion on the face (range, 0-112 FTU). In the validation study, 6 raters evaluated 11 patients with facial vitiligo twice at an interval of 2 weeks. RESULTS: One hand was measured at 32.1 ± 1.3 FTU, which was highly consistent among subjects across different age groups, sexes, and races. Facial Vitiligo Area Scoring Index showed remarkably high accuracy (concordance correlation coefficient, 0.946; smallest detectable change, 2.2 FTU) as well as high intrarater reliability (intraclass correlation coefficient, 0.903; inter-rater reliability, 0.903). LIMITATIONS: Lack of dynamic validation of responsiveness. CONCLUSION: Facial Vitiligo Area Scoring Index using the FTU is an intuitive, precise, and reliable instrument for assessing the extent of facial involvement in vitiligo patients.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications.

BACKGROUND: Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. OBJECTIVE: The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography. METHODS: Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached. RESULTS: The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. CONCLUSIONS: This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.

Excimer laser/light treatment of alopecia areata: A systematic review and meta-analyses.

BACKGROUND: The excimer laser/light (EL) has been reported to be effective for alopecia areata (AA), but its treatment response has not been systematically reviewed. OBJECTIVE: To determine the treatment response and safety of EL treatment of AA. METHODS: A comprehensive search of the Medline, EMBASE, Cochrane library, and Web of Science (from inception to December 31, 2018) was conducted to identify prospective clinical studies assessing the treatment response of EL for AA. The primary outcome was cosmetically acceptable hair regrowth (hair regrowth ≥75%); random-effects meta-analyses using generic inverse variance weighting were performed to estimate treatment responses. The study was registered with PROSPERO (CRD42019121092). RESULTS: Of 52 records initially identified, 13 full-text articles were finally assessed in terms of eligibility. A total of 9 prospective clinical studies (129 AA patients) including 5 controlled clinical trials were identified. Cosmetically acceptable hair regrowth was achieved in 50.2% (95% confidence interval 31.5%-68.9%; 8 studies). EL treatment significantly improved hair regrowth compared with untreated controls (relative risk 7.83; 95% confidence interval 2.11-29.11; 5 controlled clinical trials). No serious adverse effect was noted. CONCLUSIONS: EL treatment appeared to produce a favorable therapeutic response in AA patients. The use of EL should be encouraged for AA patients with the advantages of the non-invasiveness and no systemic effect.

Fatal course of idiopathic chronic ulcerative enteritis with panenteritis and perforation: a case report and review of literature.

BACKGROUND: Idiopathic chronic ulcerative enteritis (ICUE) is a very rare disease with high mortality. Because of clinical rarity, several small case reports have been published and there is a lack of large sample study. Preoperative definite diagnosis is difficult. Although definite treatment for ICUE is radical surgical resection, surgical decision in operative field is difficult. CASE PRESENTATION: A 77-year-old man came to the emergency department with complaints of a 1-day history of abdominal pain and abdominal distension. Abdominal computed tomography revealed ileus and focal free air. Laparotomy revealed multiple small bowel tiny perforations in the ileum. The serosa surface in the whole small bowel had small multiple yellowish tiny discolored lesions. Despite the presence of multiple mucosal ulcers in entire small bowel, the ileum including perforation site was resected segmentally. Microscopically, mucosal ulcers in resected small bowel demonstrated transmural inflammation, no granuloma, and no lymphoid aggregates. These features were consistent with a diagnosis of ICUE with panenteritis and perforation. After surgery, the patient's general condition gradually aggravated. Unfortunately, the patient died of multiple organ failure on post-operative day 14. CONCLUSION: Surgically, the decision including resection range, anastomosis or enterotomy becomes difficult in ICUE with panenteritis. According to recent 40 year's revised data, the post-operative mortality of ICUE is about 53.4%. Although ICUE is rare, its recognition is important for appropriate diagnosis and treatment. Retrospective multicenter case studies are required to determine proper treatment and improve prognosis.

Compendium of skin molecular signatures identifies key pathological features associated with fibrosis in systemic sclerosis.

OBJECTIVES: Treatment of patients with systemic sclerosis (SSc) can be challenging because of clinical heterogeneity. Integration of genome-scale transcriptomic profiling for patients with SSc can provide insights on patient categorisation and novel drug targets. METHODS: A normalised compendium was created from 344 skin samples of 173 patients with SSc, covering an intersection of 17 424 genes from eight data sets. Differentially expressed genes (DEGs) identified by three independent methods were subjected to functional network analysis, where samples were grouped using non-negative matrix factorisation. Finally, we investigated the pathways and biomarkers associated with skin fibrosis using gene-set enrichment analysis. RESULTS: We identified 1089 upregulated DEGs, including 14 known genetic risk factors and five potential drug targets. Pathway-based subgrouping revealed four distinct clusters of patients with SSc with distinct activity signatures for SSc-relevant pathways. The inflammatory subtype was related to significant improvement in skin fibrosis at follow-up. The phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signalling pathway showed both the closest correlation and temporal pattern to skin fibrosis score. COMP, THBS1, THBS4, FN1, and TNC were leading-edge genes of the PI3K-Akt pathway in skin fibrogenesis. CONCLUSIONS: Construction and analysis of normalised skin transcriptomic compendia can provide useful insights on pathway involvement by SSc subsets and discovering viable biomarkers for a skin fibrosis index. Particularly, the PI3K-Akt pathway and its leading players are promising therapeutic targets.

Comparison of 311-nm Titanium:Sapphire laser and 308-nm excimer laser treatment for vitiligo: A randomized controlled non-inferiority trial.

OBJECTIVES: The 308-nm excimer laser (EL) has been widely used for localized vitiligo. The recently developed Titanium:Sapphire laser, emits a wavelength of 311 nm, would be expected to be as effective as excimer laser in treatment of vitiligo but few controlled trials have been reported. We sought to compare the efficacy and safety of the TSL and EL as vitiligo treatments. METHODS: A randomized controlled non-inferiority trial based on split-body was conducted. Patients with stable vitiligo between June 2016 and May 2017 were enrolled. Paired symmetrical vitiligo lesions were randomized to either the EL or TSL treatment group, and treated with a 308-nm EL or a 311-nm TSL twice weekly for 12 weeks. The extent of repigmentation was assessed every 4 weeks, and the non-inferiority margin was set to 10%. We also recorded any adverse events. RESULTS: Seventy-four paired lesions in 21 patients were assigned to both the EL group or TSL group. The mean difference between two groups (EL minus TSL) was -2.862%, and the 95% confidence interval (-6.531% to 0.807%) was lower than the non-inferiority margin. No serious adverse events were noted in either group. CONCLUSIONS: The Titanium:Sapphire laser showed similar therapeutic effect to excimer laser in localized vitiligo with good safety profiles in this non-inferiority randomized controlled trial. The Titanium: Sapphire laser can serve as an alternative treatment option for localized vitiligo. Lasers Surg. Med. 51:239-244, 2019. © 2019 Wiley Periodicals, Inc.

Promotion of wound healing through low-fluence ablative fractional laser treatment in diabetic mice.

Chronic ulcers are a significant cause of morbidity in diabetic patients, which can greatly affect a patient's quality of life. While numerous methods have been developed to promote and enhance wound healing in diabetic patients, a convenient, effective treatment for diabetic ulcers has yet to be established. Here, we demonstrate the promotion of wound healing using a low-fluence (2 mJ/spot) ablative fractional laser (AFL) treatment in diabetic mice. Treatment was shown to confer increases in mRNA expression and in protein abundance of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), along with decreases in mRNA expression and protein abundance of transforming growth factor beta (TGF-ß). Taken together, these results suggest that low-fluence AFL treatment can be used to promote healing in chronic diabetic wounds.