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.

Measuring h-index and scholarly productivity in academic dermatology in Canada.

Promotion in academia heavily relies on research productivity. The h-index is a standardized metric used to quantify research productivity at the individual level. We evaluated factors associated with h -index in dermatology across select Canadian academic centers with special focus on sex and academic rank. Medical academic centers throughout Canada with dermatology training programs were included. For each faculty member, we extracted the following data from public sources: sex, graduate degree, academic rank, years since the Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) certification or equivalent, recent Canadian Institutes of Health Research (CIHR) funding and H-index (based on Scopus author profile). Log-linear univariate and multivariate regression analyses were performed to evaluate the association between h-index and these factors. An ordinal logistic regression was performed to explore sex differences in academic ranking. Our results showed that out of 300 faculty members across Canada, 155 were females (51.67%) and 145 were male (48.33%). H-index was available for 279 dermatologists. The average h-index was 8.35 (SD 11.53) and the median was 4.00 (1st quartile = 2.00, 3rd quartile = 10.00). Higher h-index was associated with more years since dermatology certification, successive academic rank, graduate degree and recent CIHR funding, but not with sex. In conclusion, h-index was not associated with sex when controlling for potential confounders. These results could reflect recent demographic changes in the field with an increase in newly appointed female dermatologists. Longitudinal assessment of academic productivity in dermatology is needed to assess the impact of continued efforts to promote equal opportunities in the field.

Top Ten Research Priorities for Psoriasis, Atopic Dermatitis and Hidradenitis Suppurativa: The SkIN Canada Priority Setting Initiative.

BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing. For those selected skin conditions, we conducted scoping reviews to identify previous priority setting exercises. We combined the results of those scoping reviews with a survey of patients, health care providers, and researchers to generate lists of knowledge gaps for each condition. We then surveyed patients and health care providers to create preliminary rankings to prioritize those knowledge gaps. Finally, we conducted workshops of patients and health care providers to create the final Top Ten lists of research priorities for each condition. RESULTS: Overall, 538 patients, health care providers, and researchers participated in at least one survey or workshop. Psoriasis, atopic dermatitis and hidradenitis suppurativa (inflammatory skin disease); chronic wounds, burns and scars (wound healing); and basal cell, squamous cell and Merkel cell carcinoma (skin cancer) were selected as priority skin conditions. Top Ten lists of knowledge gaps for inflammatory skin conditions encompassed a range of issues relevant to patient care, including questions on pathogenesis, prevention, non-pharmacologic and pharmacologic management. CONCLUSIONS: Research priorities derived from patients and health care providers should be used to guide multidisciplinary research networks, funders, and policymakers in Canada and internationally.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Representation of sex, race, and ethnicity in pivotal clinical trials for dermatological drugs.

BACKGROUND: It is of paramount importance that clinical trials are designed with adequate health equity considerations to prevent disproportionate analyses of specific demographics. OBJECTIVE: In this study, we investigated the representation of sex, race, and ethnicity in pivotal clinical trials for drugs with dermatological disease indications approved by the U.S. Food and Drug Administration between 1995 and 2019. METHODS: Thirty-six novel drugs with indications to treat dermatological diseases, approved by the U.S. Food and Drug Administration between January 1995 and December 2019 were abstracted from Drugs@FDA. The drug approval label, statistical review, official record, and trial publication were reviewed for data on disease indication, approval year, pathway, number of participants, participant demographics (sex, race, and ethnicity), location, and sponsor type. RESULTS: The overall female representation was 45.6% (n = 17,492 of 38,320). Adequate female representation was noted for five of six disease indications. Caucasians were predominantly overrepresented (80.4%; n = 28,065 of 34,890); Blacks (9.8%; n = 3242 of 33,240) and Asians (5.5%; n = 1535 of 27,696) were consistently underrepresented. Across sponsor types, there was a significant difference in the distribution of women (χ2 = 6.332; p = .042), as well as Caucasians (χ2 = 12.813; p = .002), Blacks (χ2 = 13.002; p = .002), and Hispanics/Latinos (χ2 = 7.747; p = .021). CONCLUSION: Persistence of disparities disproportionately affect the quality of data behind therapies for certain demographics; as such, enrollment practices must continue to address the issue of underrepresentation. Efforts to facilitate demographic equity among clinical trial participants must be supported to ensure that safety and efficacy conclusions are drawn from representative population samples.

Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

Vitiligo Skin Biomarkers Associated With Favorable Therapeutic Response.

Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients' responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient's response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.

Immunohistochemistry analysis reveals lysyl oxidase-like 3 as a novel prognostic marker for primary melanoma.

Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan-Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stages (P < 0.0001; χ2 test). Increased LOXL3 expression was associated with enhanced tumor thickness and mitosis. Survival analysis showed significantly worsened prognosis in primary melanoma patients when the LOXL3 expression level was higher (P = 0.043; log-rank test). Multivariate Cox regression analysis further showed that LOXL3 expression is a prognostic factor for primary melanoma patient survival (P = 0.04). LOXL3 expression is positively correlated with tumor progression and invasion, and its overexpression is associated with worse prognosis of primary melanoma patients. LOXL3 can serve as a prognostic marker to help identify primary melanoma patients at higher risks of death.

Computer-Aided Discovery of Small Molecule Inhibitors of Thymocyte Selection-Associated High Mobility Group Box Protein (TOX) as Potential Therapeutics for Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphomas (CTCL) are the most common primary lymphomas of the skin. We have previously identified thymocyte selection-associated high mobility group (HMG) box protein (TOX) as a promising drug target in CTCL; however, there are currently no small molecules able to directly inhibit TOX. We aimed to address this unmet opportunity by developing anti-TOX therapeutics with the use of computer-aided drug discovery methods. The available NMR-resolved structure of the TOX protein was used to model its DNA-binding HMG-box domain. To investigate the druggability of the corresponding protein-DNA interface on TOX, we performed a pilot virtual screening of 200,000 small molecules using in silico docking and identified 'hot spots' for drug-binding on the HMG-box domain. We then performed a large-scale virtual screening of 7.6 million drug-like compounds that were available from the ZINC15 database. As a result, a total of 140 top candidate compounds were selected for subsequent in vitro validation. Of those, 18 small molecules have been characterized as selective TOX inhibitors.

Immunotherapy for Cutaneous T-Cell Lymphoma: Current Landscape and Future Developments.

Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic, progressive primary cutaneous T-cell lymphomas (CTCLs) for which there are no curative treatments. Skin-directed therapies, such as phototherapy, radiation therapy, or topical nitrogen mustard, provide only short-term remissions. Numerous attempts with different chemotherapeutic regimes failed to achieve meaningful clinical responses. Immunotherapy seems to be a promising avenue to achieve long-term disease control in CTCL. There is compelling evidence indicating that MF and SS are immunogenic lymphomas, which can be recognized by the patient's immune system. However, CTCL uses different strategies to impair host's immunity, eg, via repolarizing the T-cell differentiation from type I to type II, recruiting immunosuppressive regulatory T-cells, and limiting the repertoire of lymphocytes in the circulation. Many currently used therapies, such as interferon-α, imiquimod, extracorporeal phototherapy, and allogeneic bone marrow transplant, seem to exert their therapeutic effect via activation of the antitumor cytotoxic response and reconstitution of the host's immune system. It is likely that novel immunotherapies such as immune checkpoint inhibitors, cancer vaccines, and chimeric antigen receptor-T cells will help to manage CTCL more efficiently. We also discuss how current genomic techniques, such as estimating the mutational load by whole genome sequencing and neoantigen calling, are likely to provide clinically useful information facilitating personalized immunotherapy of CTCL.

Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically.

Treatment strategies involving immune-checkpoint blockade (ICB) have significantly improved survival for a subset of patients across a broad spectrum of advanced solid cancers. Despite this, considerable room for improving response rates remains. The tumor microenvironment (TME) is a hurdle to immune function, as the altered metabolism-related acidic microenvironment of solid tumors decreases immune activity. Here, we determined that expression of the hypoxia-induced, cell-surface pH regulatory enzyme carbonic anhydrase IX (CAIX) is associated with worse overall survival in a cohort of 449 patients with melanoma. We found that targeting CAIX with the small-molecule SLC-0111 reduced glycolytic metabolism of tumor cells and extracellular acidification, resulting in increased immune cell killing. SLC-0111 treatment in combination with immune-checkpoint inhibitors led to the sensitization of tumors to ICB, which led to an enhanced Th1 response, decreased tumor growth, and reduced metastasis. We identified that increased expression of CA9 is associated with a reduced Th1 response in metastatic melanoma and basal-like breast cancer TCGA cohorts. These data suggest that targeting CAIX in the TME in combination with ICB is a potential therapeutic strategy for enhancing response and survival in patients with hypoxic solid malignancies.

Existing and Emerging Therapies for Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas characterized by an infiltration of malignant monoclonal T lymphocytes into the skin. Mycosis fungoides (MF), the most common subtype, and the rarer Sézary syndrome (SS), are considered the classical forms of CTCL, which, because of a varying presentation and lack of genetic and immunophenotypical markers, can often have a delayed diagnosis. With skin-directed topical treatment being the mainstay of therapy in the early stages, there is an absence of long-term curative therapies for advanced disease. Recent insight into the pathogenesis of CTCL has identified new potential therapeutic targets including the monoclonal antibody therapies, brentuximab vedotin and mogamulizumab. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, received extended approval by the US FDA in 2017 to include primary cutaneous anaplastic large-cell lymphoma and CD30-expressing MF. Mogamulizumab, an anti-CCR4 antibody, received FDA approval in 2018 for relapsed or refractory MF and SS. Further targets and therapies continue to be investigated, including the monoclonal antibody therapy alemtuzumab, an anti-CD52 antibody, and the immune checkpoint blockade therapies, pembrolizumab and nivolumab. These new and emerging targets and therapies may lead to a promising broadening of CTCL treatment options in the future.

Whole-Exome Sequencing Reveals Frequent Mutations in Chromatin Remodeling Genes in Mammary and Extramammary Paget's Diseases.

Paget's disease (PD) is an intraepidermal adenocarcinoma of the skin at the breast (mammary PD) or urogenital locations (extramammary PD [EMPD]). At present, there is lack of clarity on PD's pathogenesis, the relationship between its subtypes, and its lineage link with the underlying invasive carcinomas. Here we describe that mammary PD and EMPD have similar mutational profiles, with the most frequent recurrent mutations occurring in the chromatin remodeling genes, such as KMT2C (MLL3, 39%) and ARID2 (22%), with additional recurrent somatic mutations detected in genes previously not known to be mutated in cancers, such as CDCC168 (34%), FSIP2 (29%), CASP8AP2 (29%), and BIRC6 (24%). In paired mammary PD and underlying breast carcinoma samples, distinct gene mutations were detected, indicating that they represent independent oncogenic events. Finally, multistage EMPD tissue sequencing revealed KMT2C gene occurring early in EMPD oncogenesis, and that multifocal EMPD samples share the same early gene mutations, suggesting clonal origin of multifocal EMPD. Our results reveal similar genomic landscapes between mammary PD and EMPD, including early aberrations in chromatin remodeling genes. In addition, mammary PD and underlying breast ductal carcinomas represent independent oncogenic events. These findings provide approaches for developing diagnostic tools and therapeutic interventions for PD.

IL-10 is overexpressed in human cutaneous T-cell lymphoma and is required for maximal tumor growth in a mouse model.

A crucial question pertains to a role of IL-10 as a tumorigenic factor, or just a marker of advanced disease in cutaneous T-cell lymphoma (CTCL). Herein, we measured significantly elevated IL-10 mRNA in a cohort of skin samples of patients with CTCL. Increased IL-10 was also detected in the tumor microenvironment of an established inflammation-dependent murine model of using MBL2 T lymphoma cells. Conditioned media from MBL2 cells was able to stimulate IL-10 production in bone marrow-derived macrophages in an IL-4-dependent manner. Implanted MBL2 T-cell lymphomas in IL-10KO mice were 50% smaller, accompanied by decreased numbers of infiltrating macrophages and reduced efficiency of M2-polarization compared with wild-type mice. With anti-IL-10R mAb treatment, both wild-type tumor-bearing mice and IL-10KO mice exhibited a further growth inhibition. Our data indicate that targeting IL-10 signaling with neutralizing antibodies to IL-10 or its receptor may have a great potential for advanced CTCL therapy.

Cytoplasmic Pin1 expression is increased in human cutaneous melanoma and predicts poor prognosis.

The prolyl isomerase Pin1 is widely over-expressed or over-activated in cancers and promotes tumorigenesis. The authors investigated the expression level of Pin1 and analyzed the prognostic value of Pin1 expression using a large-scale melanoma tissue microarray study. Two independent sets of tissue microarrays were employed, including 114 melanoma cases in the discovery set and 424 in the validation set (538 cases in total), 32 normal nevi and 86 dysplastic nevi 118 cases of nevi. The subcellular Pin1 expression in different stages of melanocytic lesions and its prognostic significance were studied. High expression (IRS 0-8) of cytoplasmic Pin1 was observed in 3.13%, 8.33%, 16.49% and 22.76% of the biopsies in normal nevi, dysplastic nevi, primary melanoma and metastatic melanoma, respectively. Significant differences for cytoplasmic Pin1 staining were observed between normal nevi and metastatic melanoma (P = 0.011, χ2 test), between dysplastic nevi and primary melanoma (P = 0.046, χ2 test) and between dysplastic nevi and metastatic melanoma (P = 0.016, χ2 test). Kaplan-Meier survival analysis showed that increased cytoplasmic Pin1 expression was associated with a worse 5-year melanoma-specific survival of melanoma (P < 0.001) and metastatic melanoma patients (P = 0.004). Multivariate Cox regression analysis showed that cytoplasmic Pin1 expression is an independent prognostic factor in melanoma. Our data indicate that cytoplasmic Pin1 plays an important role in melanoma pathogenesis and progression, and serve as a potential prognostic marker for melanoma.

Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-ß/Smad Signal Pathway and Modulating YAP Subcellular Location.

Keloid may induce severe impairment of life quality for the patients, although keloid is a cutaneous benign tumor. Collagen triple helix repeat containing protein 1 (Cthrc1) was identified as a novel gene that was originally found in adventitial fibroblasts after arterial injury. To address the role of Cthrc1 in keloid, the expression level of Cthrc1 was assessed in normal skin and keloid tissue, as well as in normal fibroblasts (NFs) and keloid fibroblasts (KFs) by using quantitative PCR, Western blotting and immunohistochemical analysis. The results showed that Cthrc1 was increased in keloid tissue and KFs as compared with normal skin and NFs. Meanwhile, CCK8 and Transwell assays found the cellular proliferation and migration of KFs were increased as compared with NFs. Further, to verify the function of Cthrc1 in NFs and KFs, we increased Cthrc1 expression by transfecting lentivirus (LV) vectors LV-Cthrc1. The cellular proliferation and migration, collagen synthesis and the influence on TGF-ß and YAP signaling were tested. The cellular proliferation and migration were increased in NFs-Cthrc1 as compared with NFs-control. Meanwhile, YAP expression and nuclear-location was increased in NFs-Cthrc1. On the contrary, when Cthrc1 was overexpressed in KFs, the cellular migration was suppressed and YAP expression was reduced and transferred to cytoplasm in KFs-Cthrc1 as compared with KFs-control. But the expression level of collagen I was decreased and pSmad2/3 nucleus transfer was suppressed in both NFs-Cthrc1 and KFs-Cthrc1 by using Western blotting and immunofluorescence. Increased Cthrc1 activated NFs by promoting YAP nucleus translocation, whereas suppressed KFs by inhibiting YAP nucleus translocation. Enhanced Cthrc1 decreased collagen I in both NFs and KFs by inhibiting TGF-ß/Smad pathway. In conclusion, Cthrc1 may play a role in the pathogenesis of keloid by inhibiting collagen synthesis and fibroblasts migration via suppressing TGF-ß/Smad pathway and YAP nucleus translocation.