Keloid Patients Research Articles

BackgroundIn addition to producing pain and itching, keloids can cause psychological symptoms, including anxiety and depression. We aimed to investigate the prevalence and underlying factors of anxiety/depression in Chinese keloid patients and to explore the mediating role between social support and anxiety/depression.MethodsA total of 202 self-reported questionnaires were collected from keloid patients, including the General Information Questionnaire, Vancouver Scar Assessment Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), Dermatological Problems Quality of Life Inventory (DLQI), Social Support Rating Scale (SSRS), Simple Coping Styles Scale (SCSQ), Self-Efficacy Scale (GSES) and the Hospital Anxiety and Depression Scale (HADS).ResultsThe mean scores for anxiety and depression were 9.82 ± 2.20 and 7.96 ± 2.70, respectively. Annual income (OR = 0.258), GSES score (OR = 0.2955), pain symptoms (OR = 1.281) and coping styles (OR:3.321) were significantly associated with HADS anxiety in keloid patients (P<0.05), whereas use of support (OR = 0.607) was significantly associated with HADS depression in keloid patients (p<0.05). The area under the curve (AUC) for the combined anxiety ROC for annual income, coping styles, pain symptoms and GSES scores was 0.835. PROCESS analysis concluded that coping tendencies partially mediated the relationship between social support and depression, with the mediating effect accounting for 38.58% of the total effect.ConclusionCoping tendency in keloid patients played a partial mediating role between social support and depression. Future studies should further explore how training in coping tendencies can enhance the effectiveness of social support to more effectively prevent and reduce depressive symptoms.

Abstract Background Keloids are a common skin fibroproliferative disease that can result in severe aesthetic and functional concerns. Pruritus and pain are the most prevalent clinical manifestations of keloids. Schwann cells (SCs) variation and neuropathy within keloids contribute to these uncomfortable sensations; however the underlying mechanisms remain unclear. Objectives To explore the potential role of fibroblasts (FBs) and SCs in pruritic and pain keloids. Methods The activity of FBs and SCs was investigated using single-cell RNA sequencing (scRNA-seq) data of keloids. These bioinformatics analysis results were validated through in vitro cell culture, clinical samples, and in vivo experiments. The selected molecule was confirmed to be correlated with pain and itch and was subsequently used to treat cells in order to investigate its role in keloids. The in vivo inhibition assay was performed to evaluate its therapeutic potential. Results Our scRNA-seq analysis identified specific types of FBs and SCs were present in higher proportions in keloids and exhibited neurogenesis-related functions. Upon conducting an interaction analysis of these two cell types, we identified a critical molecule, Midkine (MDK), which is positively correlated with the patients’ pain and itching levels. Besides, MDK treatment facilitated the proliferation of SCs and their transition to a repairing phenotype, resulting in neuronal axonogenesis. This activation of repairing SCs promoted the release of substance P from nerve fibers, leading to clinical symptoms of pain and pruritus in keloid patients. Targeting MDK effectively reduces abnormal Schwann cell proliferation and subsequently inhibits the secretion of neuropeptides that trigger pain and pruritus. Conclusion Our study uncovered the interaction between FBs and SCs in the development of keloidal pain and pruritus, offering a novel therapeutic strategy to alleviate the distressing symptoms of keloids.

Keloid is a benign form of dermis tumor formed due to imbalance of collagen deposition and degradation during wound healing. Preclinical studies showed Tithonia diversifolia (Hemsley) A. Gray (T. diversifolia) potency as keloid treatment by inhibiting keloid fibroblast proliferation, collagen deposition, TGFβ1 and VEGF expression. This study aims to examine the safety and efficacy of T. diversifolia extract gel for keloid treatment in keloid patient. Fourteen keloid patients were included in the study with ratio 1:1. The participants received either T. diversifolia extract gel 2% or triamcinolone acetate cream 0.025% for 12 weeks. Evaluation of efficacy was done every 4 weeks until week 12 using Vancouver Scar Score, the patient and observer Scar assessment. Vancouver scar total score was improved in week 12 from baseline in both groups. Improvement from baseline after 12 weeks of treatment also found in patient and observer scar assessment total scale. Those scores on week 12 were similar between those on T. diversifolia extract gel 2% and triamcinolone acetate cream 0.025% treatment. Conclusions: T. diversifolia extract gel 2% is efficacious and safe for keloid treatment.

Secreted clusterin inhibits keloid formation by promoting fibroblast apoptosis.

Retrospective cohort study on the association of ATF3 gene expression with clinical prognosis in keloid patients

BackgroundThe causal relationship between keloid and mental disorders remains unclear. The aim of this study was to investigate whether keloid was causally associated with the risk of bipolar disorder (BD), anxiety, schizophrenia (SCZ), major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) using a bidirectional Mendelian randomization (MR) analysis.MethodsThe large available genome-wide association study (GWAS) dataset of keloid, BD, anxiety, SCZ, MDD and PTSD was used for summary statistics. The bidirectional MR analyses were performed using a variety of methods of analysis including inverse variance weighting, MR-Egger regression, weighted median, simple modal and weighted modal methods. Sensitivity analyses were conducted using Cochran’s Q to estimate heterogeneity, and the MR-Egger method was used to estimate horizontal pleiotropy.ResultsMR analysis showed that keloid susceptibility was associated with an increased risk of BD (OR = 1.027, 95% CI: 1.005–1.049, p = 0.015) and SCZ (OR = 1.023 (95% CI: 1.006–1.040, p = 0.006). We also observed a negative association between keloid and PTSD (OR = 0.903, 95% CI: [0.835–0.977], p = 0.011). There was no evidence for a causal relationship between keloid and anxiety (OR = 0.982, 95% CI: 0.961–1.004, p = 0.110) and MDD (OR = 0.997, 95% CI: 0.987–1.006, p = 0.476). Reverse MR analysis revealed that there was no causal relationship between keloid and the mental disorders.ConclusionThis study provides evidence that there is a link between BD, SCZ, PTSD and keloid. However, there was no causal relationship between anxiety, MDD and keloid. This study may provide important clues and references for the study of keloid and mental disorders. We urge that the mental conditions of keloid patients should be taken into account in clinical practice and that necessary psychological support should be provided.

Promoting ferroptosis of keloid fibroblasts: a key mechanism underlying the efficacy of 5-aminolevulinic acid photodynamic therapy for keloids.

Keloids are pathologic scars that result from abnormal wound healing processes following skin trauma, with a higher prevalence in the Black population. The pathogenesis of keloids is not fully understood, hindering effective treatment options for this highly disfiguring and distressing condition. Biopsies from lesional and non-lesional skin from keloid patients and healthy skin from age/gender/race-matched controls were collected and analyzed using RNA-sequencing, RT-qPCR, and immunohistochemistry. Spearman analysis was used to evaluate the correlations between biomarker expressions and clinical severity measurements. Both keloidal lesions and non-lesional skin showed a distinct transcriptomic profile compared to healthy skin. Keloids demonstrated significant upregulation of fibrosis-related markers (e.g., COL10A1, COL11A1, and BMP1). Lesional and/or non-lesional samples showed significant upregulation of key immune biomarkers belonging to T-cells (e.g., CD2, CD3D, and CD3E), T-cell/NK-cell activation/migration (e.g., CCL19, CCR7, GZMA, GZMB, and GZMK), Th1 (e.g., OASL, MX1, CCL4), Th2 (e.g., IL4R, OX40/TNFRSF4, and OX40L/TNFSF4), and Th17/22 (e.g., S100A7, S100A8, S100A9, and CCL20). Multiple immune biomarkers expression (e.g., CCL2, CXCL1, and S100A7) in lesional and/or non-lesional skin significantly and positively correlated with keloid severity parameters (e.g., keloid size, distensibility, and number). Both lesional and non-lesional keloid skin show distinct upregulation of immune axes, underscoring the role of inflammation in keloid pathogenesis and pointing to potential novel therapeutic targets.

Highlights: Previous keloid surgery mostly caused keloid recurrence. The most common symptom that accompanies keloids in surgical wounds was itching. Surgery and combination therapy were the most used therapy. Abstract: Introduction: Keloid is an abnormal scar resulting from disruptions in the wound healing process. Clinically, keloids extend beyond the original wound margins and progressively enlarge into dense, firm nodules. They can develop following various forms of trauma, including surgical procedures. Several factors contribute to keloid formation in surgical wounds, such as age, gender, genetics, skin color, hormones, incision location, wound tension, and delayed healing. Methods: This retrospective descriptive study analyzes medical records of patients diagnosed with keloids due to surgical wounds at the Department of Plastic and Reconstructive Surgery, Dr. Soetomo General Academic Hospital, Surabaya, between 2019 and 2022. Results: Among 58 keloid patients, 23 developed keloids following surgery. The most common risk factor was a history of previous keloid surgery. The majority of patients were female, aged 17–25 years, students, and had no family history of keloids. The most frequent keloid location was the chest, with an onset of ≥1 year, a size of &lt;20 cm², and associated itching. Surgical excision and combination therapy were the most commonly used treatment approaches. Conclusion: Previous keloid surgery is the primary risk factor for developing keloids in surgical wounds. Surgery and combination therapy remain the most frequently employed treatment strategies.

Management of keloid is still a challenge. Many treatment modalities are available, yet no definitive treatment protocol exists. Vitamin D3 (Vit. D3) has an anti-inflammatory role in preventing tissue fibrosis. Platelet-rich plasma (PRP) contains plentiful various peptides that have anti-inflammatory and tissue repair activities. The study aimed to assess the safety and efficacy of injecting either Vit. D3 or PRP versus their combination in keloid treatment. There were sixty keloid patients in all, randomly split into three matchedgroups for this research. Group I received an intralesional vitamin D3 injection; Group II got an intralesional PRP. While group III received both alternatively. All patients received treatment session biweekly until clinical cure or for a maximum of 4 successive sessions. Therapeutic efficacy was assessed by Verbal rating scale (VRS), Vancouver scar scale (VSS), dermoscopic, and ultrasonic examinations. Additionally, H&E and immunohistochemical expression of Caveolin-1 (Cav-1) were studied. Significant improvements in both VSS and VRS of keloid scars were detected in the three groups studied. These findings were significantly higher among patients treated by combined Vit. D3 and PRP followed by Vit. D3 monotherapy, and lastly PRP monotherapy. Parallel dermoscopic and radiological findings were detected confirming the clinical results. In the three groups studied, histopathological examination reported significant reduction in collagen with more compact orientation, and significant increase of Cav-1 immunohistochemical expression in keloid scars after treatment. Intralesional injection of either Vit. D3, PRP or their combination are safe and effective in keloid treatment.

Keloid treatment remains challenging due to high recurrence rates, particularly in patients with higher phototypes. This study aimed to assess the resolution, patient satisfaction, and recurrence rates in 79 keloids treated with a sequential non-surgical protocol combining long-term occlusion with hydrocolloid dressings, monthly injections of triamcinolone and 5-fluorouracil (5-FU), and intense pulsed light therapy. This approach is expected to lower recurrence, improve resolution, and increase patient satisfaction compared to traditional treatments. This longitudinal observational study included 79 keloids in 55 patients with Fitzpatrick phototypes III or higher. Data were collected retrospectively from medical records and clinical appointments. Patients were followed for 19-123 months after completing treatment. Outcomes evaluated included keloid resolution, patient satisfaction, and recurrence rates. The patients had a mean age of 39 years and underwent treatment for a median of 10 months. Pain was reported in 8.9% of cases, and only one recurrence (1.3%) occurred five years post-treatment. Complete resolution was achieved in 82.3% of keloids, and 94.9% of patients reported maximum satisfaction. The sequential non-surgical approach evaluated in this study demonstrated low recurrence and high satisfaction rates. Thus, it may represent a promising treatment option for keloid patients with higher phototypes.

Multi-omics analysis to explore the molecular mechanisms related to keloid.

BackgroundKeloid is a typical skin fibrotic disease with unclear mechanisms and limited therapeutic options. Fibroblast-induced fibrogenesis is a crucial cause of KD. However, the types of cells involved in fibroblast fibrogenesis in KD and the specific mechanisms are unclear. This study aimed to investigate the role of melanocyte-secreted melanin in promoting fibroblast fibrogenesis and its mechanism and to evaluate the potential therapeutic effect of intervening melanin in treating keloid.MethodsThe activity of pigmentation-related pathways in KD melanocytes was examined using single-cell RNA-sequence (scRNA-seq) analysis. Masson-Fontana staining or isolated melanin quantification detected the melanin levels and distribution in the skin and cells. Collagen deposition, wounding healing, and proliferation analysis were employed to integratively assess fibroblast fibrogenesis. After melanin treatment, bulk-seq identified fibroblasts’ differentially expressed genes (DEGs). The iron levels were detected by Perl’s staining or isolated iron quantification. Cell viability, LipidROS, and malondialdehyde assay accessed the ferroptosis levels. The therapeutic potential of ML329 was evaluated in keloid-bearing mice.ResultsWe found the enriched skin pigmentation-related pathways in the melanocytes of keloid by single-cell RNA-sequence (scRNA-seq) analysis. We further validated increased melanin levels in keloid patients. Additionally, melanin positively correlated with the Keloid Area and Severity Index in keloid. Furthermore, melanocyte-secreted melanin significantly promoted fibroblast proliferation, migration, and collagen synthesis. Mechanically, melanin increased basal cell permeability and inflammation to facilitate its transfer to the dermis, where it further activated fibroblasts by evoking iron overload and ferroptosis resistance. Consistently, iron overload and ferroptosis resistance were validated in primary fibroblasts and skin tissues of keloid patients. Inhibition of iron overload and ferroptosis resistance effectively diminish melanin-induced fibrogenesis. Interestingly, melanin induced iron overload and ferroptosis resistance in melanocytes in an autocrine manner and further stimulated keratinocytes to take up melanin to deepen skin color by upregulating the F2R-like trypsin receptor 1 (F2RL1). In vivo, the delivery of ML329, a microphthalmia-associated transcription factor (MITF) inhibitor, could suppress melanogenesis and alleviate keloid in human keloid-bearing nude mice. Meanwhile, ML329 decreased the iron content and restored the sensitivities of ferroptosis.ConclusionCollectively, melanin-lowing strategies may appear as a potential new therapeutic target for keloid.Graphical abstract

Keloids, characterized by excessive collagen deposition resulting in raised and often painful scars, profoundly affect the psychosocial well-being of adolescents, leading to anxiety, depression, and social withdrawal during a critical period of identity formation. Current literature highlights these challenges but lacks comprehensive management strategies within dermatological practice. This review identifies the need for integrated care models that combine clinical treatment with mental health support, including routine psychosocial screening, immediate counseling referrals, and adolescent-specific education programs on keloid management and emotional coping. Training dermatologists to recognize psychological distress and adopt compassionate communication is essential. Collaborative research should focus on evaluating these integrative care models and developing evidence-based guidelines. By pioneering these comprehensive strategies, dermatology practices can improve physical outcomes and significantly enhance the quality of life for adolescents with keloids, addressing both the physical and psychological scars. Future research should prioritize the longitudinal impact of these interventions on mental health and treatment adherence, establishing a new standard of care that fully supports adolescent keloid patients. By implementing these comprehensive strategies, dermatology practices can enhance physical outcomes and significantly improve the quality of life for adolescents with keloids, addressing both the physical and psychological impacts in the management of keloids in this vulnerable population.

The exact pathogenesis of keloid (KD) associated pruritus is still unknown and responds poorly to current antipruritic therapies. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in a variety of pruritus associated diseases, while its role in KD is still rather vague. The aim of this study is to explore the pathophysiological mechanism of KD-associated pruritus by detecting the correlation between the severity of pruritus and the expression of pruritogenic cytokines IL -31 and its receptor complex components, IL-31 receptor α (IL-31RA) and Onstostatin M receptor β (OSMRβ), and the number of their source cells. A total of 46 keloid tissue samples were included in this study and clinical data were recorded, of which 24 were available with both lesional and clinically adjacent uninvolved perilesional skin ( AUPS, taken at least 0.5 cm away from the keloid edge ), and 22 were available with lesional skin only. In this study, immunofluorescence detection was used to detect and compare the expression differences of IL-31 and its receptors (IL-31RA and OSMRβ) in different layers (epidermis, superficial dermis, and deep dermis) between keloid lesions and AUPS and the correlation between the IL-31 expression level and the severity of KD-associated pruritus was explored. In addition, immunofluorescence co-localization was used to explore the cell source of IL-31, and the correlation between the number of source cells and the severity of KD-associated pruritus was explored. The fluorescence intensity in epidermis and number of infiltrating cells in the dermis was quantified and normalized by ImageJ software. In this study, the KD and AUPS groups were matched for age and gender, which were not statistically different and, there was no significant difference in the sample causes and distribution between two groups. Compared with the AUPS, the number of IL-31(+) cells in the superficial and deep dermal and the total fluorescence intensity of IL-31 in the epidermis were significantly increased in the KD and they were positively correlated with the severity of pruritus. IL-31-derived cells are M2 macrophages and mast cells, but mainly from M2 macrophages. M2 macrophages in the superficial dermis of keloid are related to the severity of KD-associated pruritus. Although mast cells play an important role in the induction of pruritus, the number of infiltrated mast cells in the skin of KD patients was not correlate with the severity of KD-associated pruritus. IL-31RA was strongly expressed in the epidermis and superficial dermis of both groups, and was positively correlated with the severity of pruritus. The number of OSMRβ (+) cells in the superficial dermis of the KD was significantly higher than that of the AUPS, but has no correlation with the severity of pruritus. Our data indicate this complex dermal milieu of M2 macrophages/IL-31/IL-31RA network could be useful a therapeutic target for KD-associated pruritus. The superficial dermis may be an important injection layer for the pharmaceuticals and other treatment of KD-associated pruritus. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

To establish, evaluate and compare three recurrence prediction models for keloid patients using machine learning methods. We enrolled 301 keloid patients who underwent surgery and postoperative radiotherapy, dividing them into a training set (70%) and a validation set (30%). Three recurrence prediction models were established in the training set: the logistic regression model, the decision tree model, and the random forest model. We then evaluated and compared the performance of these models in the validation set, using metrics such as accuracy, sensitivity, specificity, recall, precision, kappa coefficient, and the area under the ROC curve (AUC). We developed three machine learning-based prediction models for keloid recurrence. KAAS, mean arterial pressure levels, postoperative complications, and the proportion of inflammatory cells played crucial roles in these models. The decision tree model outperformed both the random forest and logistic regression models in terms of accuracy, and it also exhibited the highest overall precision. Regarding AUC, logistic regression performed the best, followed by random forest and decision trees. This study established three prediction models for keloid recurrence using machine learning techniques, highlighting the significance of KAAS, blood pressure levels, postoperative complications, and inflammatory cell proportions. When compared from various dimensions, the logistic regression model demonstrated the most favorable prognostic performance in terms of AUC.

Introduction: Keloid is an abnormal wound healing condition influenced by various factors, including adiponectin levels and genetic predisposition. The role of adiponectin in keloid formation, particularly concerning familial and non-familial history, remains unclear. This study aims to compare adiponectin levels in keloid patients with and without a familial history of keloid formation. To compare adiponectin levels in patients with familial and non-familial keloid history. Methods: This observational analytic study utilized a cross-sectional design involving 40 keloid patients. Participants underwent anamnesis, dermatological examination, and blood sampling to measure serum adiponectin levels using enzyme-linked immunosorbent assay (ELISA). Data were analyzed descriptively using IBM SPSS Statistics version 21. Results: Keloid was more frequently observed in female patients, particularly in the 18–25-year age group. The mean serum adiponectin level among all participants was 11.01±8.34 μg/ml. In patients with a familial history of keloid, 40.0% had low adiponectin levels, while 42.5% of those without a familial history also exhibited low levels. Statistical analysis revealed no significant difference in adiponectin levels between the two groups, suggesting that low adiponectin levels are a common feature in keloid patients regardless of genetic predisposition. Conclusion: Low adiponectin levels are prevalent among keloid patients, but they are not significantly associated with a familial history of keloid formation. Further research is needed to explore the mechanisms linking adiponectin to keloid development.

To investigate effectiveness of a novel suture method-stepwise progressive ultra-tension-reducing suture method in closing high-tension wounds on the chest, back, and limbs. A retrospective analysis was conducted on 25 patients with high-tension wounds on the chest, back, and limbs who were treated with stepwise progressive ultra-tension-reducing suture method between January 2022 and December 2022. Among the patients, there were 8 males and 17 females, with an average age of 30.5 years (range, 18-56 years). All wounds after scar or tumor resection were located on the chest, back, upper limbs, and lower limbs in 8, 6, 9, and 2 cases, respectively. The size of wounds ranged from 3.5 cm×2.8 cm to 40.0 cm×15.0 cm. All patients were advised to use topical silicone-based treatments postoperatively. The protrusion of the incision, the height of the protrusion, and the duration of the tension reduction effect were observed. The scar formation at the incision site at 6 months after operation was observed, the scar appearance was evaluated by Vancouver Scar Scale (VSS) score, and the scar width was measured. The patient's satisfaction and adverse reactions to incisions were also evaluated. The incisions significantly elevated, with a height of 0.3-2.5 cm, and the tension reducing effect lasted for 8.5-18.0 weeks after operation, with an average of 13.6 weeks. All incisons healed by first intention. One patient experienced transient hyperpigmentation, which resolved spontaneously. Three keloid patients showed localized redness postoperatively, and 2 experienced local recurrence, which improved significantly after treatment with triamcinolone, 5-fluorouracil injections, and laser therapy. All patients were followed up 6.0-13.5 months, with an average of 10.1 months. At 6 months after operation, all patients had linear scars, with VSS scores ranging from 1.0 to 3.5 (mean, 2.0). The width of the scars ranged from 0.5 to 3.0 mm (mean, 1.4 mm). The patients expressed satisfaction with the effectiveness. The stepwise progressive ultra-tension-reducing suture method for high-tension wounds can effectively reduce the tension at the wound edges, providing a prolonged tension-reducing effect and satisfactory effectiveness.

Purpose: To determine the efficacy and clinical outcomes of compound betamethasone and triamcinolone acetonide on interleukin-6 (IL-6) and interleukin-17 (IL-17) in keloid management. Methods: This study was a retrospective analysis of 118 keloid patients treated at The First Affiliated Hospital of Hebei North University, Zhangjiakou, China from January 2020 to December 2022. Patients were randomly divided into Group A (comprising 62 patients who received compound betamethasone) and Group B (comprising 56 patients who received triamcinolone acetonide). Treatment efficacy after 6 months using the Vancouver Scar Scale (VSS), changes in IL-6 and IL-17 levels, and incidence of treatment-related adverse reactions were compared in both groups. Results: Group A demonstrated significantly higher overall response rate compared to Group B (p &lt; 0.05). Both groups showed significant reductions in IL-6 and IL-17 levels after treatment (p &lt; 0.05). However, Group A showed significantly lower IL-6 and IL-17 (p &lt; 0.05) and significantly higher VSS scores t Group B (p &lt; 0.05). Incidence of adverse reactions was comparable between the groups (p &gt; 0.05). Conclusion: Compound betamethasone shows superior efficacy in reducing IL-6 and IL-17 levels and improves scar appearance in keloid patients comparable to triamcinolone acetonide. Prospective studies with larger sample sizes to evaluate the efficacy of various treatments or combination therapies should be conducted.

Research on keloid is limited by the lack of proper in vitro and animal model reflecting in vivo status. Based on heterogeneity of keloid and important role of endothelial cells in its pathogenesis, a novel 3D in vitro keloid spheroid prepared with keloid fibroblasts and endothelial cells was evaluated in this study. Commercial cell lines of keloid fibroblasts and endothelial cells were used at various cellular ratios to generate keloid spheroids to determine the optimal condition. Keloid spheroids from three keloid patients were also made and their usefulness as in vitro models, including their responses to drugs, were assessed. Spheroids with higher endothelial cell proportions exhibited increased viability and propagation ability. Patient-derived keloid spheroids showed heterogeneity which might reflect individual clinical conditions. The optimal ratio of fibroblasts to endothelial cells was determined to be 4:1 for keloid spheroids based on gene expression and viability analyses. Patient-derived keloid spheroid showed better keloidal changes in genetic expressions than 2D monolayer culture. Spheroids exhibited varied responses and resistance to each drug used for keloids, depending on the cell type used. 3D keloid spheroids might provide an effective in vitro model for investigating disease pathogenesis and appropriate treatment modalities for future precision medicine.