Introduction: Intralesional triamcinolone acetonide (TAC) is an accepted management option for paediatric keloid. TAC is a corticosteroid with five times the potency of hydrocortisone and acts by inhibiting fibroblast growth and thus keloid size. Dermatological adverse effects of TAC are common, but repeated high-dose intralesional TAC can cause the rare complication of Cushing syndrome and suppression of the hypothalamic–pituitary–adrenal (HPA) axis. Case: We report the case of an 11-year-old female referred for worsening lower limb striae and low serum cortisol. Prior to referral, intralesional TAC was administered by a general practitioner to a left lower limb keloid which had developed following an orthopedic intervention. A total of five injections were administered over 4 months: a cumulative dose of 150 mg (equivalent to 700 mg hydrocortisone). The last dose was administered 6 months prior to referral. The morning serum cortisol was low (<13.8 nmol/L) with a concomitantly low adrenocorticotropic hormone (ACTH 0.41 pmol/L) level, consistent with suppression of the HPA axis secondary to exogenous steroids. Renin (84.80 mU/L), aldosterone (280.40 pmol/L), testosterone (0.31 nmol/L), estradiol (85.9 pmol/L) and thyroid function were normal. Physiological oral hydrocortisone replacement was promptly commenced, with education on adrenal crisis and sick days while awaiting recovery of the HPA axis. Conclusion This case illustrates the serious complication of Cushing syndrome with secondary HPA axis suppression due to repeated intralesional TAC therapy for paediatric keloid scars. Factors such as appropriate paediatric doses, size of the keloid, site of injection (dermal, not subcutaneous), and frequency of injections should all be given due consideration before using TAC. Clinicians prescribing steroids to children should be aware that suppression of the HPA axis is a very real and life-threatening complication and that steroids should be prescribed judiciously.
Child ; Keloid ; Triamcinolone

BACKGROUND

Keloids and hypertrophic scars are overgrowth of fibrous tissue after damage to the skin. There have been various published treatment modalities for these lesions. Currently, there are still no published studies on the use of laser-assisted drug delivery for hypertrophic scars and keloids in the Philippine setting.

To determine the efficacy and safety of laser-assisted drug delivery versus intralesional steroid injection alone for the treatment of keloid and hypertrophic scar.

This was a single center, randomized single-blind controlled study. Participants were randomly assigned into a control group (intralesional steroid injection) or a treatment group (laser-assisted drug delivery). The procedure was done monthly for four sessions. Assessment of lesions using the Vancouver Scar Scale was done at baseline and monthly post-sessions.

A total of 42 participants completed the study, which was divided into two groups of 21 samples each. Results showed that the mean difference in overall skin score from baseline to fourth treatment session was significantly lower in the laser-assisted drug delivery group than the intralesional group (–0.48±0.75 vs. –0.24±0.54, t=2.31, p=0.026). No adverse events were noted throughout the study period.

It is a promising option to use non-ablative fractional CO2 laser-assisted drug delivery as the treatment outcome was comparable to using intralesional steroid injection as monotherapy for keloids and hypertrophic scars.

OBJECTIVES: Keloids are fibrotic skin disorders characterized by excessive collagen deposition and a high recurrence rate, closely associated with inflammatory mediators. However, existing epidemiological studies are limited by confounding factors and reverse causality, making it difficult to establish causation. This study aims to investigate the causal relationship between circulating cytokines and keloids using Mendelian randomization analysis. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with circulating cytokines (exposures) and keloids (outcomes) were extracted from genome-wide association study (GWAS) summary datasets. Eligible SNPs were selected as instrumental variables (IVs). Exposure data were derived from a cytokine GWAS including 8 293 Finnish participants, and outcome data from a keloid GWAS based on the UK Biobank. The inverse-variance weighted (IVW) method served as the primary analytical approach to estimate causal effects, supplemented by weighted median (WME), MR-Egger regression, and other sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test, while Cochran's Q test evaluated heterogeneity. Leave-one-out analysis was used to verify robustness and consistency. A reverse MR analysis was also conducted, with keloid as the exposure and cytokines as outcomes, to rule out reverse causation. RESULTS: IVW analysis identified significant positive causal associations between two cytokines and keloids-macrophage migration inhibitory factor (MIF) [odds ratio (OR)=2.081, 95% confidence interval (CI) 1.219 to 3.552, P=0.007] and monocyte chemoattractant protein-1 (MCP-1) (OR=1.673, 95% CI 1.036 to 2.701, P=0.035). Conversely, stem cell factor (SCF) showed a negative causal relationship with keloids (OR=0.518, 95% CI 0.269 to 0.998, P=0.049). Results from the MR-Egger and weighted median analyses were consistent with IVW findings. No evidence of horizontal pleiotropy was observed (P>0.05). Except for interleukin-6 (P=0.014), no heterogeneity was detected in other cytokines. Leave-one-out analysis further confirmed the robustness of the causal associations. In reverse MR analysis, keloids were causally related only to β-nerve growth factor (beta-NGF) (OR=1.048, 95% CI 1.002 to 1.095, P=0.039), with no heterogeneity or pleiotropy detected in most cytokines (P>0.05). CONCLUSIONS MIF and MCP-1 exhibit positive causal associations with keloid formation, while SCF shows a negative causal relationship. These findings provide new evidence for the causal involvement of inflammatory cytokines in keloid pathogenesis and offer potential molecular targets for developing novel keloid therapies.
Humans ; Keloid/blood* ; Mendelian Randomization Analysis ; Cytokines/genetics* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Chemokine CCL2/genetics* ; Interleukin-6/genetics* ; Macrophage Migration-Inhibitory Factors/genetics* ; Male ; Stem Cell Factor/blood* ; Female ; Intramolecular Oxidoreductases

Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.
Humans ; Keloid/genetics* ; Nomograms ; Algorithms ; Calibration ; Machine Learning

OBJECTIVE: To review the research progress of the principle and clinical application of keloid core excision technique. METHODS: The literature on keloid core excision technique at home and abroad in recent years was extensively reviewed, and the principle, development history, indications, advantages and disadvantages of this technique were summarized, and the existing controversies were analyzed. RESULTS: Keloid core excision is a technique to remove the inner fibrous core from the keloid and cover the defect with the keloidal flap. It reduces the wound tension, yields good aesthetic results in the treatment of ear keloids, and reduces the recurrence rate of keloids combining with adjuvant therapies. CONCLUSION The keloid core excision technique has specific advantages, yet its overall efficacy remains controversial. Further studies are imperative to explore the mechanisms regarding keloid recurrence and the vascular supply principles of the keloidal flap. It is also necessary to define appropriate surgical indications and safety protocols of this technique.
Humans ; Keloid/pathology* ; Recurrence ; Surgical Flaps/pathology* ; Plastic Surgery Procedures ; Treatment Outcome

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.
Female ; Humans ; Male ; Asian People ; Cicatrix, Hypertrophic/diagnostic imaging* ; Extremities ; Keloid/diagnostic imaging* ; Prospective Studies ; Adult

Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-‍β (TGF-‍β)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1‍‍-‍‍15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.
Adolescent ; Cells, Cultured ; Exosomes/metabolism* ; Fibroblasts/metabolism* ; Humans ; Keloid/pathology* ; Melanins/metabolism* ; Melanocytes/pathology* ; Pilot Projects ; Skin/metabolism* ; Transforming Growth Factor beta/metabolism*

Objective: To explore the clinical effects of pulsed dye laser (PDL) dynamically combined with triamcinolone acetonide (TAC) in the treatment of keloids. Methods: A retrospectively observational study was conducted. From April 2015 to October 2020, 34 keloid patients (46 keloids) who met the inclusion criteria were admitted to Huaihe Hospital of Henan University. The patients were divided into TAC group and dynamic treatment group according to their treatment methods. There were 18 patients (26 keloids) in TAC group, including 8 males and 10 females, aged (30±12) years, who were treated with TAC injection alone. There were 16 patients (20 keloids) in dynamic treatment group, including 6 males and 10 females, aged (26±11) years, who were treated with TAC injection, PDL, or PDL combined with TAC injection according to the Vancouver scar scale (VSS) score before each treatment. Before the first treatment (hereinafter referred to as before treatment) and 12 months after the first treatment (hereinafter referred to as after treatment), the keloids were assessed by VSS, patient and observer scar assessment scale (POSAS), and the effect of keloids on the quality of life of patients was evaluated with dermatology life quality index (DLQI) scale. Twelve months after treatment, the curative effect of keloid was evaluated according to the VSS score and the effective rate was calculated. The first effective time and the cumulative times of TAC injection at the first effective time, the number of follow-up and the occurrence of adverse reactions of keloids within 12 months after treatment were recorded, and the incidence of adverse reactions was calculated. Data were statistically analyzed with paired sample t test, independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: The total VSS scores of patients' keloids in TAC group and dynamic treatment group 12 months after treatment were significantly lower than those before treatment (with t values of 7.53 and 8.09, respectively, P<0.01), and the total scores of pigmentation and vascularity in VSS and POSAS, the total POSAS score, and the DLQI scale score were significantly lower than those before treatment (with Z values of -3.71, -4.04, -4.21, -4.11, -3.76, -3.73, -3.92, and -3.93, respectively, P<0.01). The total scores of pigmentation and vascularity in VSS and POSAS of patients' keloids in dynamic treatment group 12 months after treatment were significantly lower than those in TAC group (with Z values of -2.03 and -2.12, respectively, P<0.05). Twelve months after treatment, the effective rate of patients' keloids in dynamic treatment group was significantly higher than that in TAC group (χ²=3.88, P<0.05). The first effective time of patients' keloids in dynamic treatment group was 5.5 (2.0, 6.0) months, which was significantly shorter than 6.0 (2.3, 10.3) months in TAC group (χ²=4.02, P<0.05). The cumulative times of TAC injection at the first effective time of patients' keloids in dynamic treatment group was 3.2±1.7, which was significantly less than 4.2±1.8 in TAC group (t=2.09, P<0.05). The number of follow-up of patients' keloids within 12 months after treatment in dynamic treatment group was significantly more than that in TAC group (t=-2.94, P<0.01), and the total incidence of adverse reactions was lower than that in TAC group but without statistically significant difference (P>0.05). Conclusions: Compared with TAC injection alone, PDL dynamically combined with TAC in the treatment of keloid can shorten the effective time, reduce the number of TAC injection, and improve the patient's compliance and clinical efficacy.
Female ; Humans ; Keloid/pathology* ; Lasers, Dye/therapeutic use* ; Male ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Triamcinolone Acetonide/therapeutic use*

In re-cent 20 years, the development of cell biology technology has promoted the research of keloid. Keloid fibroblasts (KFbs) are the main effector cells in keloid, which are closely related to the occurrence and development of keloid. It is significantly different in terms of biological characteristics and gene expression between KFbs and normal fibroblasts. This articles reviews the characteristics of KFbs from multiple perspectives, describing its biological character- istics in details including microstructures, metabolic character- istics, and proliferation properties, and introducing the main characteristics of heterogeneity and genomics of KFbs. The further research on KFbs will help to elucidate the pathogenesis of keloids and provide valuable strategies for the prevention and treatment of keloids.
Fibroblasts/metabolism* ; Humans ; Keloid/pathology*

BACKGROUND: Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients' quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids. METHODS: In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients' interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids. RESULTS: Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration > 15 years (OR, 2.98; P = 0.046). CONCLUSION Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration > 15 years.
Case-Control Studies ; Humans ; Keloid/epidemiology* ; Quality of Life ; Retrospective Studies ; Rheumatic Diseases ; Risk Factors