Effectiveness of various methods of manual scar therapy.

BACKGROUND: The skin is a protective barrier of the body against external factors, and its damage leads to a loss of integrity. Normal wound healing results in a correct, flat, bright, and flexible scar. Initial skin damage and patient specific factors in wound healing contribute that many of these scars may progress into widespread or pathologic hypertrophic and keloid scars. The changes in cosmetic appearance, continuing pain, and loss of movement due to contracture or adhesion and persistent pruritis can significantly affect an individual's quality of life and psychological recovery post injury. Many different treatment methods can reduce the trauma and surgical scars. Manual scar treatment includes various techniques of therapy. The most effectiveness is a combined therapy, which has a multidirectional impact. Clinical observations show an effectiveness of manual scar therapy. MATERIAL AND METHODS: The aim of this work was to evaluate effectiveness of the scar manual therapy combined with complementary methods on the postoperative scars. Treatment protocol included two therapies during 30 min per week for 8 weeks. Therapy included manual scar manipulation, massage, cupping, dry needling, and taping. RESULTS: Treatment had a significant positive effect to influence pain, pigmentation, pliability, pruritus, surface area, and scar stiffness. Improvement of skin parameters (scar elasticity, thickness, regularity, color) was also noticed. CONCLUSION: To investigate the most effective manual therapy strategy, further studies are needed, evaluating comparisons of different individual and combined scar therapy modalities.

Effect of the combination of photobiomodulation therapy and the intralesional administration of corticoid in the preoperative and postoperative periods of keloid surgery: A randomized, controlled, double-blind trial protocol study.

Keloid scars are characterized by the excessive proliferation of fibroblasts and an imbalance between the production and degradation of collagen, leading to its buildup in the dermis. There is no "gold standard" treatment for this condition, and the recurrence is frequent after surgical procedures removal. In vitro studies have demonstrated that photobiomodulation (PBM) using the blue wavelength reduces the proliferation speed and the number of fibroblasts as well as the expression of TGF-ß. There are no protocols studied and established for the treatment of keloids with blue LED. Therefore, the purpose of this study is to determine the effects of the combination of PBM with blue light and the intralesional administration of the corticoid triamcinolone hexacetonide on the quality of the remaining scar by Vancouver Scar Scale in the postoperative period of keloid surgery. A randomized, controlled, double-blind, clinical trial will be conducted involving two groups: 1) Sham (n = 29): intralesional administration of corticoid (IAC) and sham PBM in the preoperative and postoperative periods of keloid removal surgery; and 2) active PBM combined with IAC (n = 29) in the preoperative and postoperative periods of keloid removal surgery. Transcutaneous PBM will be performed on the keloid region in the preoperative period and on the remaining scar in the postoperative period using blue LED (470 nm, 400 mW, 4J per point on 10 linear points). The patients will answer two questionnaires: one for the assessment of quality of life (Qualifibro-UNIFESP) and one for the assessment of satisfaction with the scar (PSAQ). The team of five plastic surgeons will answer the Vancouver Scar Scale (VSS). All questionnaires will be administered one, three, six, and twelve months postoperatively. The keloids will be molded in silicone prior to the onset of treatment and prior to excision to assess pre-treatment and post-treatment size. The same will be performed for the remaining scar at one, three, six, and twelve months postoperatively. The removed keloid will be submitted to histopathological analysis for the determination of the quantity of fibroblasts, the organization and distribution of collagen (picrosirius staining), and the genic expression of TGF-ß (qPCR). All data will be submitted to statistical analysis. Trial registration: This study is registered in ClinicalTrials.gov (ID: NCT04824612).

Evaluating outcomes of pulsed dye laser therapy combined with intralesional triamcinolone injection after surgical removal of hypertrophic cesarean section scars.

BACKGROUND: Recently, pulsed dye laser (PDL) combined with triamcinolone intralesional injection (TAILI) has been introduced for surgical scar prevention. However, little is known about this procedure's effectiveness in preventing hypertrophic scar following surgical scar removal. OBJECTIVES: This study aimed to evaluate the outcome of early intervention using PDL combined with TAILI after surgical removal of hypertrophic cesarean section (CS) scars. METHODS: The medical records of 35 patients who underwent early intervention using PDL and TAILI after removal of hypertrophic CS scars were retrospectively reviewed. The scars' average Vancouver Scar Scale (VSS) scores before scar removal and 3 months after the final treatment were compared. RESULTS: The patients received 4.23 treatments on average and were followed up for a mean period of 7.74 months. The mean final VSS was 3.11 ± 1.52 and was significantly lower than that of the previous VSS (9.29 ± 1.74, p = 0.000). VSS of the previous CS scar, and the presence or absence of keloid formation in other areas, was associated with treatment outcome (p = 0.003 and 0.008, respectively). CONCLUSIONS: Early intervention using PDL combined with TAILI could prevent the recurrence or progression of hypertrophic CS scarring after surgical scar removal.

The Most Current Algorithms for the Treatment and Prevention of Hypertrophic Scars and Keloids: A 2020 Update of the Algorithms Published 10 Years Ago.

BACKGROUND: In 2010, this Journal published my comprehensive review of the literature on hypertrophic scars and keloids. In that article, I presented evidence-based algorithms for the prevention and treatment of these refractory pathologic scars. In the ensuing decade, substantial progress has been made in the field, including many new randomized controlled trials. To reflect this, I have updated my review. METHODS: All studies were evaluated for methodologic quality. Baseline characteristics of patients were extracted along with the interventions and their outcomes. Systematic reviews, meta-analyses, and comprehensive reviews were included if available. RESULTS: Risk factors that promote hypertrophic scar and keloid growth include local factors (tension on the wound/scar), systemic factors (e.g., hypertension), genetic factors (e.g., single-nucleotide polymorphisms), and lifestyle factors. Treatment of hypertrophic scars depends on scar contracture severity: if severe, surgery is the first choice. If not, conservative therapies are indicated. Keloid treatment depends on whether they are small and single or large and multiple. Small and single keloids can be treated radically by surgery with adjuvant therapy (e.g., radiotherapy) or multimodal conservative therapy. For large and multiple keloids, volume- and number-reducing surgery is a choice. Regardless of the treatment(s), patients should be followed up over the long term. Conservative therapies, including gel sheets, tape fixation, topical and injected external agents, oral agents, and makeup therapy, should be administered on a case-by-case basis. CONCLUSIONS: Randomized controlled trials on pathologic scar management have increased markedly over the past decade. Although these studies suffer from various limitations, they have greatly improved hypertrophic scar and keloid management. Future high-quality trials are likely to improve the current hypertrophic scar and keloid treatment algorithms further.

The effectiveness of long Pulsed Nd:YAG Laser alone for treatment of keloids and hypertrophic scars versus its combination with bleomycin.

BACKGROUND AND OBJECTIVES: Pathological scars are benign hyper-proliferative growths of dermal collagen that causes severe psychological and physical problems. This study was performed to assess and compare safety and clinical efficiency of combined pulsed Nd-YAG laser and intralesional bleomycin versus pulsed Nd-YAG laser alone to treat the hypertrophic scars and keloids. PATIENTS AND METHODS: Randomly, 40 patients with hypertrophic scars or keloids were divided into two groups A and B. Group A were handled by pulsed Nd:YAG laser and intralesional bleomycin while group B were handled by pulsed Nd:YAG laser only. Response was assessed subjectively by clinical imaging and modified Vancouver Scar Scale (mVSS). While for objective evaluation, skin biopsies were taken from volunteer patients before and after treatment, and were examined by Hematoxylin and eosin staining (H&E) and Masson trichrome staining. RESULTS: Our study demonstrated almost complete improvement in 4 (20%) patients, partial improvement in 16 (80%) patients and 0 patient with no improvement in group A. Furthermore, in group B, we demonstrated almost complete improvement in 2 (10%) patients, partial in 14 (70%) patients and no improvement in 4 (20%) patients. Modified Vancouver Scar Scale reduced from 10.15 to 3.5 in group A and from 11.05 to 4.95 in group B. Elastica Masson-Goldner staining and Hematoxylin and eosin staining showed that treatment in both groups structurally changed tissue collagen. CONCLUSION: Long-pulsed Nd-YAG laser combined with intralesional bleomycin could be a promising way for treatment of keloids or hypertrophic scars.

Hyperbaric oxygen treatment on keloid tumor immune gene expression.

BACKGROUND: Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work. METHODS: From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC). RESULTS: Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification. CONCLUSION: HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.

Effects of in vivo application of an overnight patch containing Allium cepa, allantoin, and pentaglycan on hypertrophic scars and keloids: Clinical, videocapillaroscopic, and ultrasonographic study.

Several therapeutic approaches have been described for their treatment of hypertrophic scars and keloids, but to date, the optimal treatment has not been established yet. Our in vivo study was conducted to evaluate the effect of a medical device consisting in an adhesive patch containing onion extract (Allium cepa) 10%, allantoin 1%, and pentaglycan 4% (Kaloidon patch) on hypertrophic scars and keloids. Thirty-nine patients with hypertrophic scars and seven patients with keloids were asked to apply an adhesive patch containing Allium cepa, allantoin, and pentaglycan once/day for at least 8 h consecutively, for 24 weeks. Patients were reevaluated 6 weeks (T6), 12 weeks (T12), and 24 weeks (T24) after starting the treatment through POSAS scale v 2.0, ultrasonographic, and videocapillaroscopic assessment. The investigated medical device was able to induce a significant improvement of POSAS starting from T12, with a positive amelioration trend until T24. However the patient-assessed POSAS sub-items showed improvement already after 6 weeks, whereas a significant improvement of the observer-assessed POSAS sub-items was observed only after 12 weeks (P < .001). Ultrasonography and intravital videocapillaroscopy confirmed a significant improvement of skin scars thickness (P < .001) and vascularization (P < .001) after 12 weeks of medical device application at least, with increasing improvement until T24. Applying an adhesive patch containing Allium cepa, allantoin, and pentaglycan once a day for at least 8 consecutive hours seems to be able to improve the clinical and morphological characteristics of the scars of the skin in 24 weeks.

Hyperbaric oxygen treatment on keloid tumor immune gene expression / 中华医学杂志(英文版)

BACKGROUND@#Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work.@*METHODS@#From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC).@*RESULTS@#Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification.@*CONCLUSION@#HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.

[Examining the pathogenesis and therapeutic strategy of keloids from the perspective of systemic inflammation].

Keloid is a disease that is difficult to cure and has a high recurrence rate. In the past, research on keloid focused on keloid cells themselves and the therapeutic strategy limited to local treatment, whereas the role of systemic factors in the process of occurrence and development of disease was usually neglected. Based on the literature reports and clinical evidence, we propose that the pro-inflammatory constitution of keloid patients can serve as a systemic factor to interact with local factors such as skin lesion, and thus leads to the initiation and development of keloid. The classical theory about close relationship between visceral malfunctions and skin diseases described in traditional Chinese medicine has provided supporting evidence. Therefore, we suggest that systemic anti-inflammatory therapy should be included in the design of future keloid therapeutic strategies and be verified by the clinical trials. Additionally, the therapeutic strategies of traditional Chinese medicine including anti-dampness, detoxing and heating removing can also be employed as a part of systemic treatment of keloids.

Effects of hyperbaric oxygen therapy on the expression levels of the inflammatory factors interleukin-12p40, macrophage inflammatory protein-1ß, platelet-derived growth factor-BB, and interleukin-1 receptor antagonist in keloids.

BACKGROUND: Our study aimed to screen and explore the expression of inflammatory factors in keloid patients and to investigate how hyperbaric oxygen (HBO) therapy affects the expression levels of interleukin-12p40 (IL-12p40), macrophage inflammatory protein-1ß (MIP-1ß), platelet-derived growth factor-BB (PDGF-BB), and interleukin-1 receptor antagonist (IL-1Ra). OBJECTIVE: 30 patients were randomly selected and divided into the following 3 groups: keloid samples from keloid patients treated with HBO therapy (A), keloid samples from keloid patients treated without HBO therapy (B), and normal control skin samples derived from individuals who had no clear scarring (C). Each group included 10 samples. METHODS: Inflammatory factors in the keloid tissues were measured with the MILLIPLEX multiplexed Luminex system. Hematoxylin and eosin staining, immunohistochemical staining, and Western blotting were used to observe the morphological differences in different tissues and the expression levels. RESULTS: The expression levels of inflammatory mediators, including IL-12p40, MIP-1ß, PDGF-BB, and IL-1Ra, in keloid tissues were significantly different from those in samples of normal skin. Hematoxylin and eosin staining showed significantly greater inflammatory infiltration in keloid tissue. Significantly different expression levels were observed in group A, B, and C. CONCLUSION: Significantly altered levels of inflammatory factors in the samples from keloid patients were observed, suggesting that formation of a keloid is potentially related to inflammatory responses. HBO therapy could significantly affect the expression levels of IL-12p40, MIP-1ß, PDGF-BB, and IL-1Ra, indicating that the effects of HBO therapy are associated with the attenuation of inflammatory responses.

Scarring and wound healing.

Following injury, the skin undergoes a wound healing process culminating in the formation of a mature scar. Millions of patients worldwide are left with scars every year as a result of trauma or surgery. Scars can be painful, disfiguring and disabling, yet patients report that clinicians are often dismissive of their concerns, unable to identify pathological scars and unaware of treatment options. The normal wound healing process comprises three overlapping stages: inflammation, proliferation and remodelling. In some patients this process is deranged, resulting in the formation of hypertrophic or keloid scars. Clinicians can minimize the risk of these pathological scars developing with good surgical technique and wound aftercare. If pathological scars do form, they should be identified early and patients referred for treatment, most often topical or intralesional corticosteroids. In resistant cases, pathological scars may be treated with phototherapy, radiotherapy or surgical resection.

Combined Therapeutic Strategies for Keloid Treatment.

BACKGROUND: Recent advances in keloid management favor the administration of combination therapy over monotherapy. OBJECTIVE: The authors evaluated the safety and efficacy of combination therapy to treat keloids using fractional lasers, cryotherapy, and intralesional corticosteroids. MATERIALS AND METHODS: The authors performed a retrospective study involving 35 Korean patients. Each patient underwent treatment using the 1,550 nm nonablative fractional erbium-glass laser, followed by the 10,600 nm ablative fractional carbon dioxide laser. Laser treatment was immediately followed by the administration of superficial cryotherapy and intralesional triamcinolone injection. Therapeutic efficacy was assessed using the Vancouver Scar Scale (VSS) score and the 7-point patient self-assessment score. RESULTS: The mean total and subcategory VSS scores showed statistically significant improvements. The height and pliability scores showed the most significant and quickest responses to the combination therapy. The patients reported remarkable improvement in itching, pain, and limitations of motion after a single combination therapy session. Twenty patients were followed up for 1 year after the discontinuation of the combination treatment, and the recurrence was observed only in one patient. No significant adverse effects were observed throughout the follow-up period. CONCLUSION: Combination keloid therapy using fractional lasers, superficial cryotherapy, and intralesional triamcinolone injection is safe and more effective than individual monotherapies.

Hyperbaric oxygen therapy can ameliorate the EMT phenomenon in keloid tissue.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been widely used in the clinical setting. In this study, HBOT therapy was evaluated for its ability to ameliorate the epithelial-to-mesenchymal transition (EMT) phenomenon in keloid tissue. METHODS: Keloid patients were randomly divided into two groups: keloid patients (K group, 9 patients) and keloid patients receiving HBOT (O group, 9 patients). A third group with normal skin (S group, 9 patients) was established for control. Before HBOT and surgery, a laser Doppler flowmeter was used to measure the keloid blood supply of patients in the O group. Hematoxylin and eosin (H&E) staining was used to observe morphology. E-cadherin, ZO-1, vimentin, fibronectin, vascular endothelial growth factor (VEGF), and hypoxia inducible factor (HIF)-1α were measured by immunofluorescence staining and Western blot analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the mRNA expression level of these factors as well. RESULTS: In the O group, keloid blood perfusion was significantly reduced after patients received HBOT. Compared with the K group, lower expression levels of vimentin, vibronectin, VEGF, and HIF-1α were observed in the O group, whereas the expression of E-cadherin and ZO-1 was significantly higher. The mRNA expression of E-cadherin and ZO-1 was also increased after HBOT. CONCLUSIONS: The expression levels of factors related to the EMT phenomenon were significantly reversed in keloid patients after they received HBOT, indicating that HBOT may be an effective therapy against the EMT phenomenon in keloid patients.

Efficacy of Autologous Platelet Concentrates as Adjuvant Therapy to Surgical Excision in the Treatment of Keloid Scars Refractory to Conventional Treatments: A Pilot Prospective Study.

BACKGROUND: After conventional treatments, keloid scars show varying degrees of recurrence. The aim of this study was to assess the efficacy and safety of platelet-rich plasma in the treatment of postoperative keloid scars refractory to conventional treatments. METHODS: This pilot prospective study was conducted in 17 patients with keloid scars who did not respond to 4 injections of cortisone or radiotherapy after extralesional resection of keloid. Platelet-rich plasma was injected intraoperatively and then 3 times with a 1-month interval. The primary end point was the complete remission of keloid scars 2 years posttreatment. Scar pruritus severity was scored before and after treatment. The study protocol was approved by the ethics committee and authorized by the French National Agency. This trial was registered at ClinicalTrials.gov, identifier NCT02922972. RESULTS: Nine keloid scars (53%) were completely resolved at 2 years, and 5 (29%) completely relapsed after treatment. Pruritus severity score was significantly lower at 2 years compared with baseline (1.33 ± 0.97 before treatment and 0.40 ± 0.63 at 2 years, P < 0.003). The mean Vancouver Scar Scale score significantly improved (8.18 ± 2.38 before treatment and 3.82 ± 1.98 at 2 years, P < 0.001). CONCLUSIONS: Injecting platelet-rich plasma is an effective and safe method as adjunctive therapy to resection for treating keloid scars refractory to conventional therapy.

Techniques for Optimizing Surgical Scars, Part 2: Hypertrophic Scars and Keloids.

Surgical management of benign or malignant cutaneous tumors may result in noticeable scars that are of great concern to patients, regardless of sex, age, or ethnicity. Techniques to optimize surgical scars are discussed in this three-part review. Part 2 focuses on scar revision for hypertrophic and keloids scars. Scar revision options for hypertrophic and keloid scars include corticosteroids, bleomycin, fluorouracil, verapamil, avotermin, hydrogel scaffold, nonablative fractional lasers, ablative and fractional ablative lasers, pulsed dye laser (PDL), flurandrenolide tape, imiquimod, onion extract, silicone, and scar massage.

Advances in fractional technology for skin rejuvenation, skin tightening, drug delivery, and treating scars and skin defects.

The development of fractional photothermolysis has revolutionized the treatment of skin scarring, rejuvenation, and tightening. By creating targeted microthermal zones and leaving surrounding tissue intact, this concept has provided the field with efficacious results, with less downtime and a better safety profile. This has started to change the paradigm of what is considered first-line treatment for scarring and rejuvenation. While originally applied to nonablative lasers, fractionation has now been employed in ablative, quality-switched, picosecond, and novel hybrid fractional lasers. Furthermore, other energy-based technologies, such as radiofrequency, have adopted the concept of fractionation in an attempt to optimize the balance of efficacy, downtime, and side effects. Herein, we describe how the ever-expanding repertoire of fractional devices is applied to the treatment of scarring, skin rejuvenation, and tightening. In addition, newer applications, such as transdermal drug delivery, are being developed by using fractional devices. Growing experience with these devices has broadened their relevance to more skin types and body sites than ever. Ultimately, the knowledge of appropriate treatment parameters is paramount and allows for the safe and effective treatment of a variety of patients with numerous devices.

Advanced Management of Severe Keloids.

Keloids negatively impact the health and quality of life of many affected dermatologic patients. Treating keloids is often difficult, and suboptimal responses are frequent. Fortunately, there are many treatment options available to the clinician that may lead to improved clinical outcomes. We present a review of currently available therapeutic options. Intralesional steroid injection remains the first-line treatment for keloids. Imiquimod, direct interferon therapy, or intralesional 5-flurouracil may alleviate the need for excessive corticosteroid therapy. Radiation and laser therapy are emerging therapeutic options that have demonstrated efficacy in reviewed studies. Given the unsatisfactory outcomes associated with pressure dressings, vitamin E, ablative laser, and surgical excision, these options should be avoided in keloid management. Further research is needed to evaluate the efficacy and recurrence associated with the reviewed therapeutics.