Keloid Research Articles

Management of Keloid Scars with Radiotherapy

Keloid scars are a challenging dermatological condition characterized by excessive scar tissue formation beyond the boundaries of the original wound. This review explores the epidemiology and clinical significance of keloid scars, emphasizing the substantial impact they have on patients' quality of life and psychosocial well-being. The theoretical framework delves into the definition of keloid scars, identifies risk factors contributing to their development, discusses potential complications, and outlines current management strategies. The discussion section evaluates the role of radiotherapy in managing keloid scars, providing insights into its mechanisms of action, efficacy, and safety. The conclusion emphasizes the importance of a personalized approach to keloid scar management, with radiotherapy as a valuable therapeutic option.

Skin care for scars: Where we have been and what's new

AbstractBackgroundThe process of scar formation and wound healing is an important topic as different skin types can heal diversely. Scars of all ranges, from fine line scars that are barely a bother to hypertrophic and keloid scars accompanied by bothersome symptoms, have been trouble to treat with many diverse products and hypotheses historically. The diverse appearance of scars is astounding with colors, shapes, sizes, and symptoms, including pain and pruritis, affecting patients differently.MethodsThis paper will dive into the diverse treatments of scar therapy and different published studies done to prove efficacy, along with different scar subtypes.ResultsTreatments mentioned are topical and consist of silicone‐based products, as well as non‐silicone‐based products, like onion extract, green tea, Aloe vera, hydrocolloid dressings, vitamin A derivatives, vitamin E, vitamin D, moist exposed burn ointment, imiquimod, and mitomycin.ConclusionIn sum, wound healing is a difficult process and patient outcomes vary depending on skin and scar types, thus scar therapies should continue to be studied before concluding the best skin care for scars.

Modern view on the problem of keloid scars

Modern view on the problem of keloid scars

Metformin ointment may relieve hypertrophic and keloid scars.

Metformin ointment may relieve hypertrophic and keloid scars.

Ubiquitin-specific peptidase 11 promotes development of keloid derived fibroblasts by de-ubiquitinating TGF-β receptorII

BackgroundKeloid scars occur as a result of abnormal wound healing caused by trauma or inflammation of the skin. The progression of keloids is dependent on genetic and environmental influences. The incidence is more prevalent in people with darker skin tones (African, Asian and Hispanic origin). Studies have demonstrated that transforming growth factor (TGF) β/Smad signalling has an essential function in keloid as well as that USP11 could modulate the activation of TGFβ/Smad signalling and impact the progression of the fibrotic disease. Nonetheless, the potential mechanisms of USP11 in keloid were still unclear. The authors postulated that USP11 up-regulates and augments the ability of proliferation, invasion, migration and collagen deposition of keloid-derived fibroblasts (KFBs) through deubiquitinating TGF-β receptor II (TβRII). MethodsFibroblast cells were isolated from keloid scars in vitro. Lentivirus infection was utilized to knockdown and over-express the USP11 in KFBs. Influence of USP11 on proliferation, invasion and migration of KFBs, and expression level of TβRII, Smad2, Smad3, α-SMA, collagen1 and collagen3 were assayed by CCK8, scratching, transwell, Western blot and real-time quantitative polymerase chain reaction. The interactions between USP11 and TβRII were examined using ubiquitination assays and co-immunoprecipitation. To further confirm the role of USP11 in keloid growth, we performed animal experiments. ResultsResults show that down-regulated USP11 markedly suppressed the ability of proliferation, invasion and migration of keloid derived-fibroblasts in vitro and reduce the expression of TβRII, Smad2, Smad3, αSMA, collagen1 and collagen3. In addition, over-expression of USP11 demonstrated the contrary tendency. Ubiquitination experiments and co-immunoprecipitation demonstrated that USP11 was interacting with TβRII and deubiquitinated TβRII. Interferences with USP11 inhibited growth of keloid in vivo. Additionally, we have verified that knockdown of USP11 has no significant effect on normal skin fibroblasts. ConclusionUSP11 elevates the ability of proliferation, collagen deposition, invasion and migration of keloid–derived fibroblasts by deubiquitinating TβRII.

Pruritus in keloid scars: mechanisms and treatments.

Keloids occur after cutaneous injury and can cause distress due to physical appearance and associated symptoms such as pain and pruritus. Keloid-associated pruritus is a common manifestation and has negative impacts on quality of life. The mechanism underlying this type of pruritus is multifactorial and thought to involve small nerve fiber damage, neurogenic inflammation, and a Th2-predominant inflammatory response. Various agents have been shown to reduce keloid pruritus, including intralesional corticosteroids, botulinum toxin A, 5-fluorouracil, and bleomycin. Other treatment modalities such as cryotherapy and hyperbaric oxygen therapy are also effective. Future treatments targeting the mechanisms involved in keloid-associated itch could provide improvements in pruritus and quality of life in these patients, but further studies on the efficacy of these agents are needed.

Comparison of the efficacy and safety of intralesional triamcinolone injection with the combination of triamcinolone, five fluorouracil, and hyluronidase enzyme in the treatment of keloids and hypertrophic scars

Hypertrophic and keloids scars are frequent benign disorders. These disorders occur due to the deposition of aberrant collagen in the scar tissue and can cause significant clinical presentations such as itching, discomfort, and disfigurement. Many therapeutic approaches have been proposed for their treatment without any acceptable outcomes. Methods After receiving ethical committee approval, a randomized prospective control trial was done in the clinic of plastic surgery at Suez Canal University Hospital for 3 months, from June 2023 to September 2023. 30 patients of both sexes and above the age of 14 were enrolled in the study and classified into two equal groups of 15 each: group (A) patients injected with triamcinolone alone, and group (B) patients injected with the combined therapy. All lesions were evaluated at 4, 8, and 12 weeks of injection. Scars were evaluated by the patient and observer scar assessment scale (POSAS) score. Complications such as atrophy of the skin, superficial ulcers, and telangiectasia have also been reported during or after injection. Results At 12 weeks of injection, both doctors and patients gave remarkably lower patient and observer scar assessment scale scores compared with those before injection, and there was a statistically significant difference between both groups. Group (B) scars improved more than group (A) scars in terms of itching, discomfort, pain, movement limitation, and aesthetic concern. Recurrence occurred only in group (A) patients. Conclusion The injection of the combined solution is effective more than triamcinolone alone. It results in a faster response, and an acceptable aesthetic outcome with few adverse effects.

Deep Deltoid Ligament Reconstruction Utilizing Suture Augmentation via an Arthroscopically- Assisted Approach: A Novel Technique and Case Series

Category: Trauma; Arthroscopy Introduction/Purpose: Deltoid ligament rupture is a common occurrence in the setting of acute ankle fractures. The indications for surgical restoration of the deltoid ligament complex vary considerably throughout the literature. If medial ankle instability exists after ankle fracture fixation, repair or reconstruction of the deltoid ligament complex may be performed, which is traditionally done via an open approach. While the superficial deltoid is easily accessed with an open approach, the deep deltoid ligament is extremely difficult to visualize. We present a novel technique for reconstruction of the deep deltoid ligament complex utilizing suture augmentation via an arthroscopically-assisted approach and present our outcomes. With this method, the deep deltoid ligament disruption is easily visualized and reconstructed in a minimally invasive manner through an accessory anteromedial arthroscopy portal. Methods: This is a technique guide and retrospective case series. Data was obtained via chart review including pre-operative, intraoperative, and post-operative follow ups. Variables such as age, weight, body mass index (BMI), sex, side, history of previous ankle surgery, preoperative ambulatory status, length of hospital stay, as well as disposition were documented. Radiographs were reviewed for evidence of restoration of the medial clear space as well as hardware position and bony union. In addition, a technique guide was developed using expert surgeon experience and opinion while using this novel technique. Results: 7 patients who underwent this novel technique were reviewed with an average follow up time of six months (3-8 months). All patients suffered bimalleolar or trimalleolar equivalent fractures. Patients were indicated for deep deltoid ligament reconstruction if medial ankle instability existed intraoperatively with valgus stress testing under fluoroscopy. Medial clear space decreased from a mean 11mm preoperatively to 3.3mm postoperatively. 6 patients returned to ambulation without brace by three months postoperatively. One patient demonstrated increased medial clear space measured at 6.6mm postoperatively and residual pain on follow up, but was treated conservatively and able to progress to weight bearing as tolerated by 6 months. One patient developed a keloid scar that required a steroid injection. No postoperative infections occurred. Conclusion: Deep deltoid ligament reconstruction utilizing suture augmentation via an arthroscopically-assisted approach should be considered in patients who have residual medial ankle instability after ankle fracture fixation. This novel technique allows visualization of the deep deltoid ligament complex and reconstruction in a minimally invasive manner via an accessory anteromedial arthroscopy portal. Our short term outcomes demonstrate success in restoring ankle function and radiographic parameters of the medial clear space. Further studies are needed to evaluate long term postoperative functional outcomes, stability, and development of post-traumatic arthritis.

Therapeutic management of a keloid scar after cortisone dermatitis

Therapeutic management of a keloid scar after cortisone dermatitis

Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.

Extensive keloid scarring in a dark‐skinned woman

Extensive keloid scarring in a dark‐skinned woman

Börjeson–Forssman–Lehmann syndrome: delineating the clinical and allelic spectrum in 14 new families

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS.

Therapeutic role of exosomes and conditioned medium in keloid and hypertrophic scar and possible mechanisms.

Exosomes, ranging from 40 to 160nm in diameter, are extracellular lipid bilayer microvesicles that regulate the body's physiological and pathological processes and are secreted by cells that contain proteins, nucleic acids, amino acids and other metabolites. Previous studies suggested that mesenchymal stem cell (MSC)-derived exosomes could either suppress or support keloid and hypertrophic scar progression. Although previous research has identified the potential value of MSC-exosomes in keloid and hypertrophic scar, a comprehensive analysis of different sources of MSC-exosome in keloid and hypertrophic scar is still lacking. This review mainly discusses different insights regarding the roles of MSC-exosomes in keloid and hypertrophic scar treatment and summarizes possible underlying mechanisms.

Outcomes of omega variant keystone flap in conjunction with single fraction radiotherapy for helical keloids: A comprehensive one-year follow-up study

Achieving esthetically pleasing results for helical keloids can be challenging. This study aims to share the results of a treatment approach for helical keloids, which involves complete excision and reconstruction using an omega variant keystone flap, followed by a single fractional radiotherapy. The current study is a retrospective review of 25 helical keloids in 21 patients from May 2021 to March 2023. All keloid cases were excised entirely. We covered the defect with an omega variant keystone flap followed by a single fraction of 9.5 or 10Gy radiotherapy within 24h after surgery. The mean follow-up period was 12 months. The primary outcome was recorded as recurrence versus non-recurrence. The secondary outcome was scores assessed by the Patient and Observer Scar Assessment Scale. All 25 keloids in 21 patients completed the treatment protocol, with a follow-up interval of 12 months. Of these patients, 100% had successful treatment of their keloids without any keloid recurrence. The postoperative course was uneventful except for one case of early postoperative flap congestion, which was spontaneously healed without any interventions. Scores obtained from the Patient and Observer Scar Assessment Scale showed that pain, itchiness, color, stiffness, thickness, irregularity, vascularity, pigmentation, thickness, relief, and pliability significantly improved. (p<0.001). We successfully reconstructed helical keloids using an omega variant keystone flap after keloid removal followed by 9.5 or 10Gy single fractional radiotherapy without any keloid recurrence in one-year follow-ups.

Autocrine IL-6 drives cell and extracellular matrix anisotropy in scar fibroblasts

Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular actin network, suggesting that cell alignment initiates ECM patterning. Keloid fibroblasts produce elevated levels of IL-6, and autocrine IL-6 production is both necessary and sufficient to induce cell and ECM alignment, as evidenced by ligand stimulation of normal dermal fibroblasts and treatment of keloid fibroblasts with the function blocking IL-6 receptor monoclonal antibody, tocilizumab. Downstream of IL-6, supracellular organization of keloid fibroblasts is controlled by activation of cell-cell adhesion. Adhesion formation inhibits contact-induced cellular overlap leading to nematic organization of cells and an alignment of focal adhesions. Keloid fibroblasts placed on isotropic ECM align the pre-existing matrix, suggesting that focal adhesion alignment leads to active anisotropic remodeling. These results show that IL-6-induced fibroblast cooperativity can control the development of a nematic ECM, highlighting both IL-6 signaling and cell-cell adhesions as potential therapeutic targets to inhibit this common feature of fibrosis.

Cryotherapy versus corticosteroid phonophoresis in the treatment of keloid scars: A randomized clinical trial

Background. Keloid scars negatively impact patients' physical and mental well-being, causing pain and itching. Several methods exist for treating keloids by modulating and improving scar characteristics. Purpose. To investigate and compare the effects of cryotherapy and corticosteroid phonophoresis on patients with keloid scars. Methods. This was a randomized clinical trial. Sixty patients, both male (28) and female (32), with keloid scars were divided into two equal groups. Group A received cryotherapy for 12 weeks (n=30), while Group B underwent corticosteroid phonophoresis for the same duration (n=30). Assessments were made pre-treatment, after 6 weeks, and after 12 weeks of treatment. Results. Post-treatment comparisons between the two groups revealed statistically significant reductions in VSS at both 6 weeks and 12 weeks in favor of Group A (p &lt; 0.05). Conclusion. Cryotherapy demonstrated a significantly greater positive impact on scar measurements in patients with keloid scars than corticosteroid phonophoresis.

Symptomatic Diastasis Rectus Abdominis in Children: Review of Current Management Options and Presentation of a Novel Minimally Invasive Epifascial Repair Technique

Several surgical techniques are available for an adult patient collective with diastasis recti. Only few research papers addresses the treatment options of diastasis of the rectus abdominis in children. In this case series, we present a new technique of epifascial repair as a novel possibility in successfully repairing defects of the anterior abdominal wall using minimally invasive surgery. In this case series, we present an epifascial repair technique for patients with a diastasis recti with a dehiscence cranial of the umbilicus. Four pediatric patients with symptomatic rectus diastasis were treated with this new surgical technique. All procedures were conducted successfully, and no recurrence was observed in the follow up. All patients showed clinical regression of the rectus diastasis without any postoperative abdominal wall protrusion and good improvement of the symptoms. Intraoperative intraperitoneal air loss, postoperative scar keloid, thermal lesions due to Ultracision and one seroma/hematoma after the removal of the drain were minor complications observed during the follow-up.

549 Foot Syndactyly: Operative Management, Postoperative Webspace Splinting, and a Retrospective Review of Cases Across 15 Years at a Tertiary Plastics Centre

Abstract Aim Syndactyly of the foot is a common congenital abnormality, with an estimated prevalence of 1 in 2,000. While thought to be more common than hand syndactyly, there is considerably less discussion of foot syndactyly in the literature. We describe our operative approach to foot syndactyly and a postoperative technique for splinting with silicone moulds to reduce webcreep complication. We sought to further characterise the nature of, and postoperative outcomes for, foot syndactyly cases managed at our centre. Method We performed a retrospective analysis of cases of paediatric foot syndactyly managed at our centre over the last 15 years. Results 47 patients (52 primary foot syndactyly repair operations), involving 75 webspaces were identified (80.0% simple syndactyly, 1.3% complex, 18.7% not specified). 54.7% webspaces were incomplete syndactyly (21.3% complete, 24.0% not specified). The second webspace was the most commonly involved (57.3%). Median age of first operation was 47.5 months. Of patients with documented follow-up, 24.1% of webspaces developed a complication. Complications included webcreep (13.8%), keloid (5.2%) and hypertrophic (5.2%) scarring, graft loss (3.4%), infection (3.4%), overgranulation (1.7%), clinodactyly (1.7%), and suture granuloma (1.7%). The most common documented repair technique involved ‘V-shaped’/’triangular’ interdigitating local flaps. There was no difference in webcreep rates between FTSG and STSG repairs. Conclusions Webcreep remains the most common complication of foot syndactyly, and one parents must be suitably informed about. This work adds to a relatively small body of work internationally and describes a simple method to help reduce post-operative contracture.

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid

Background: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. Objectives: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. Methods: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. Results: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. Conclusion: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

P29 The use of adjunct oral methotrexate as primary prevention for keloid scarring following syndactyly release surgery

Abstract A 12-month-old Asian female underwent syndactyly release surgery with advancement flap closure of the first web space of the right hand. The procedure was complicated by enlarging keloids over the surgical site and dactylitis, a rare complication with only a few previously reported cases [Muzaffar AR, Rafols F, Masson J et al. Keloid formation after syndactyly reconstruction: associated conditions, prevalence, and preliminary report of a treatment method. J Hand Surg Am 2004; 29: 201–8. https://doi.org/10.1016/j.jhsa.2003.10.017]. Initial treatment of the keloid scarring with intralesional triamcinolone under general anaesthetic was unsuccessful. Subsequently, we elected to surgically excise the keloids closing with a full-thickness skin graft from the groin, with adjunct oral methotrexate (0.4 mg kg–1 weekly) for 9 months post-surgery. The use of oral methotrexate for this indication is rarely reported: one series included two cases of successful keloid suppression with 4 years of follow-up [Muzaffar et al.] and another series of four patients with successful keloid suppression after surgery for syndactyly with dactylitis [Tolerton SK, Tonkin MA. Keloid formation after syndactyly release in patients with associated macrodactyly: management with methotrexate therapy. J Hand Surg Eur 2011; 36: 490–7]. Low-dose methotrexate exerts anti-inflammatory effects by stimulating adenosine A2 receptors and increasing adenosine release at sites of inflammation, such as surgical sites [Muzaffar et al.]. In our patient, methotrexate was well-tolerated, keloid recurrence and dactylitis were avoided, and range of movement and functioning of the digits was maintained. Keloid formation after syndactyly release poses a complex management challenge and we propose methotrexate should be considered as an adjunct to reduce recurrence risk.