Review on various combination therapies for the treatment of Hypertrophic scars and keloids

Laser-assisted drug delivery in the treatment of keloids: A case of extensive refractory keloids successfully treated with fractional carbon dioxide laser followed by topical application and intralesional injection of steroid suspension

Treatment of hypertrophic scars and keloids: a review

Both keloid and hypertrophic scars are common benign skin lesions manifested by hyperplasia of fibroblasts. Clinically, this will not only have physiological effects on patients, but also cause psychological damage. However, there is no unified standard treatment method at present. Intralesional corticosteroid injection alone and corticosteroid combined with botulinum toxin type A has been gradually found to be useful for the treatment of keloid and hypertrophic scars, but the difference in efficacy between the two is controversial. A systematic search was made of the relevant experiments from Web of Science, PubMed, Scopus, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The scores of Visual Analog Scale (VAS), Vancouver Scar Score sheet (VSS), scar thickness, itching degree and patient satisfaction after the combination of corticosteroid and botulinum toxin type A were superior than those after corticosteroid (P<0.05). Compared with corticosteroid alone, corticosteroid combined with botulinum toxin type A is more effective in the treatment of keloid and hypertrophic scar. Although clinical case studies for the treatment of keloid or hypertrophic scars are limited, it is necessary and helpful to understand the effectiveness of corticosteroid combined with botulinum toxin type A in the treatment of keloid or hypertrophic scars. 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 .

Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatments for hypertrophic scars and keloids. MEDLINE, Embase, Scopus, and the Cochrane Collaboration database were searched from inception to March 2019 for randomized control trials of treatments for hypertrophic and keloid scars that included 20 or more patients. Outcomes evaluated included the standardized mean reduction in scarring and adverse events. The type of scar and the demographic features were analyzed for their effect on clinical outcome. Based on 25 included clinical trials, intralesional injection (64.1% [95% CI 60.8-67.5%]) may be more effective than physical (29.9% [95% CI 28.9-30.9%]) or topical treatments (34% [95% CI 31.8-36.8%]). Combination of 5-fluorouracil and triamcinolone (9:1 dilution) appeared superior among intralesional treatments for keloids. Ablative laser and pulsed-dye laser were the most useful laser treatments. Regression modeling showed laser treatment response was linked to Fitzpatrick skin type (p = 0.002). Adverse events were uncommon for all treatments and mostly transient. Intralesional treatments for keloid and hypertrophic scars may be the most reliable treatment option to improve pathologic scars, while laser treatment may have specific benefits for Fitzpatrick skin types I-III over types IV-VI. Management of pathological scars is an area of critical need, where appropriate treatment can have a significant impact on quality of life.

Hypertrophic scar has always been the top priority of post-burn intervention. Specialists from multiple disciplines have dedicated enormous efforts expanding the knowledge in understanding the etiology of hypertrophic scar formation and establishing the scientific evidence of effective management of hypertrophic scar. The devotion and pursuit of these scientists and clinicians has been especially meaningful for the population in Asia since it has been well proven that hypertrophic scar was endemic to the Asian population comparing to the Caucasians. Besides early intervention, functional outcomes and long-term quality of life for people with extensive burn injuries have been investigated by different researchers and further substantiate the importance of long-term continuum of rehabilitation programs [1, 2].

The treatment of keloid and hypertrophic scars remains a challenging clinical problem despite numerous proposed therapies reported in the literature. This is due to the fact that the mechanisms that bring about keloid/hypertrophic scars are not completely understood. This article reviews the pertinent literature regarding the pathophysiology and management of keloid and hypertrophic scars. A computerized literature search using MEDLINE was conducted for published articles on keloid and hypertrophic scars. The medical subject headings "keloid" or "hypertrophic scar" were combined with "treatment" or "management" or "mechanisms" or "pathophysiology" using the Boolean operator "AND" to narrow the searches. A review of selected relevant literature was undertaken. Numerous advances have been made in understanding the process of formation of wound healing and scar formation. This increased knowledge has led to the introduction of new treatments as well as to a better understanding of how older treatments work. These include surgical excision, intralesional steroid injection, cryotherapy, laser therapy, irradiation, mechanical compression dressing, silicone sheet applications, intralesional interferon injection, or combination of techniques. Many of the treatment modalities have a defined biologic basis while others are based on anecdotal reports. Presently there is still no single, reliable and effective treatment protocol for keloid and hypertrophic scars. However, surgical excision followed by postoperative intralesional steroid injection seems to provide a reasonable treatment outcome with low recurrence rate.

Hypertrophic and keloid scars result from abnormal wound healing and can have a variable response to a number of available treatment modalities. The evolution of laser treatments in recent years has shown a wide range of clinical applications including their use in the treatment of scars. We investigated the effectiveness of a 1470 nm diode laser using an intralesional optical fibre delivery device in the treatment of hypertrophic and keloid scars. We evaluated its safety and efficacy as a novel and minimally invasive treatment alternative for scar modulation and volume reduction. A prospective cohort study was performed involving 21 patients with hypertrophic scars (HS) (n = 9) and keloids (n = 12) resulting from various aetiology. Patients were treated with one to three treatment sessions. Comprehensive evaluations were performed using the Vancouver Scar Scale, Doppler ultrasound, Cutometer, Mexameter and PeriCam PSI. Scar thickness was reduced by an average of 0.308 ± 0.138 cm (p < 0.001). In particular the two subgroups showed a significant 27.7% and 28.2% reduction in scar thickness of HS and Keloids, respectively. Scar firmness showed a significant improvement of 1.2% (p < 0.05) for HS, though for keloids this was 0.4% (p = 0.26). Keloids had a significant reduction in pigmentation at 21.3%. Blood perfusion had a significant reduction of 29.6% in HS and 22.7% in Keloids. Overall VSS total score improvement of 42% in the HS and at 37.9% in the Keloid subgroup. No adverse events such as hypo/hyperpigmentation, skin infection, or recurrence were reported. This study shows that the intralesional 1470 nm bare-fibre diode laser significantly improved hypertrophic and keloid scars based on both subjective and objective analyses and supports this type of laser therapy as a safe and effective minimally-invasive treatment option.

Hypertrophic and keloid scarring is a known complication of dermabrasion facial resurfacing, although only a very small fraction of patients experience it. Treatment with intralesional corticosteroid injections and flashed pumped vascular dye laser is recommended in the literature. The treatment of keloid and hypertrophic scars using intralesional 5-fluorouracil (5-FU) injections has been well described, but there is no literature regarding use of the same treatment for postdermabrasion hypertrophic and keloid scars. In this case report, we describe a 67-year-old woman with persistent postdermabrasion facial hypertrophic and keloid scars that were treated at our scar clinic using intralesional 5-FU injections.

Bleomycin is a known chemotherapeutic agent whose beneficial effects have been recently shown in the treatment of keloids and hypertrophic scars, however, it is unclear how effective it is in comparison with corticosteroids. We aimed to compare the safety and efficacy of intralesional bleomycin versus intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Sixty patients were divided into two groups and treated by intralesional injection of triamcinolone (20 mg/ml) or bleomycin (1.5mg/ml). The treatments were repeated every 3 weeks until the lesions flattened or for a maximum of six sessions. The clinical improvement was evaluated using the Japan scar workshop (JSW) scar scale (JSS) and the physician global assessment of flattening of the lesions. Side effects were also noted and recorded. 55 patients completed the study, 4 patients from the bleomycin group and 1 patient from the triamcinolone group dropped out of the study. In both groups, the total JSS scores decreased significantly after treatment compared to baseline (p< 0.001); however, the difference between groups was not statistically significant after treatment (p= 0.052). Moreover, the degree of flattening of the lesions was comparable between groups (p= 0.933). Side effects in the triamcinolone group were Hypopigmentation(55.2%), atrophy(51.7%), and telangiectasia(41.4%) and in bleomycin group included persistent pain after injection (61.5%), ulceration (69.2%), hyperpigmentation(76.9%), and secondary infection (34.6%). Intralesional bleomycin (1.5mg/ml) is effective as triamcinolone(20 mg/ml) in the treatment of keloids and hypertrophic scars, however, bleomycin should be used carefully, due to adverse events such as pain, ulceration, and hyperpigmentation.

BackgroundTreatments including intralesional corticosteroid injection, pressure therapy, cryotherapy, and various laser therapies have had limited success for keloids and hypertrophic scars.ObjectiveThis trial evaluated the efficacy of a combination of 578 nm copper bromide laser and the more traditional intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to scar color.MethodsKeloids or hypertrophic scars of 12 Korean patients were treated five times by the combined treatment at 4-week intervals. Clinical improvement was assessed by the physicians' global assessment (PGA) comparing pre- and post-treatment photographs, as well as 4 weeks after the last treatment. Erythema intensity was quantified using a mexameter.ResultsMost scars showed significant clinical improvement in PGA and decreased erythema intensity after 5 treatments. All patients showed improvements in symptoms like pruritus.ConclusionThe combined treatment is effective for keloids and hypertrophic scars, especially when the telangiectatic portion of the scars is prominent. The adjunctive use of 578 nm copper bromide laser decreased the telangiectatic side effects of an intralesional corticosteroid injection by reducing the vascular components of scars.

Background: The hypertrophic and keloid scars are thick , raised, disfiguring areas of skin with abnormal prolonged inflammatory response of wound healing process and overproduction of collagen. Carbon dioxide (CO2) laser has been used in the treatment of hypertrophic scar and keloids for more than 20 years. Aim of Study: To evaluate the effect of (CO2) laser in treatment of keloid and hypertrophic scar with use of intralesional triamcinolone acetonide (kenacort) 40 mg/ml as adjuvant therapy. Methodology: The study was done on 22 patients in Imam al-Sadiq teaching hospital in Hilla city with dividing the patients randomly in to two groups ,one group treated with four sessions of intralesional corticosteroids and the second group treated with four sessions of intralesional corticosteroids with carbon dioxide laser.

BackgroundKeloids and hypertrophic scars are pathological wound healing responses characterized by excessive scar tissue formation, presenting significant challenges to both patients and healthcare systems globally. Existing evidence demonstrates that mesenchymal stem cell–derived extracellular vesicles (MSC-EVs) can attenuate collagen deposition and contraction in scar tissue; however, their application in the treatment of hypertrophic scars and keloids remains largely at the preclinical stage. This systematic review aims to critically assess preclinical studies on the therapeutic efficacy of MSC-EVs in the management of keloids and hypertrophic scars. The review synthesizes findings from controlled and interventional studies, focusing on the use of MSC-EVs in animal models of these scars and their application in human subjects with raised scars following skin injury.MethodsA total of 15 studies involving 253 animals were identified through a comprehensive search of the PubMed, Cochrane, Embase, MEDLINE Complete, Web of Science, CNKI, and Wanfang databases, covering the period from their inception to August 29, 2025. The aim was to evaluate the effects of MSC-EV therapy on keloids and hypertrophic scars through a meta-analysis of the standardized mean difference (SMD) in preclinical animal models. Meta-analyses were conducted using Stata 18 software.ResultsMeta-analysis indicated that compared with the control group, MSC-Exos treatment group can significantly reduce. The dimensions of hypertrophic scars and keloids [(SMD) −2.78, 95% confidence interval (CI) −3.88–1.69)]. Also attenuate other outcomes, such as Collagen Type I [SMD = −4.39, 95%CI: −5.96–2.81], Collagen Type III [SMD = −5.19, 95%CI: −6.93–3.44], migration and proliferation of skin fibroblasts, and the expression of Transforming Growth Factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in scar tissue.ConclusionThe meta-analysis supports the therapeutic potential of MSC-EVs in the treatment of keloids and hypertrophic scars, as demonstrated in preclinical animal models. MSC-EV therapy has been shown to downregulate the dimensions of hypertrophic scars and keloids, inhibit collagen deposition, and reduce migration and proliferation of skin fibroblasts. Additionally, MSC-EVs suppress the expression of TGF-β1 and α-SMA in scar tissue. These findings highlight MSC-EVs as a promising therapeutic approach for managing keloids and hypertrophic scars.

The treatment of keloids and hypertrophic scars has been difficult and a recent French study showed that bleomycin has been useful in the treatment of these lesions. To determine the effectiveness and safety of bleomycin in the treatment of hypertrophic scars and keloids when this drug is administered through multiple superficial punctures. We applied bleomycin to keloids and hypertrophic scars in 13 patients using a multiple-puncture method on the surface of the skin. All patients were given bleomycin at a concentration of 1.5 IU/ml. Clinical response after treatment was classified according to the following scale: complete flattening (100%), highly significant flattening (>90%), or significant flattening (75-90%). The clinical response was very positive in all cases: complete flattening in six cases, highly significant flattening in six cases, and significant flattening in one case. Two patients presented a recurrence as a small nodule 10 and 12 months after the last infiltration. These clinical findings show that administration of bleomycin in keloids and hypertrophic scars shows promise and needs further investigation.

Lasers have been used in the treatment of hypertrophic scars and keloids for more than 20 years. Different laser systems have been examined; among them pulsed dye lasers are currently considered the laser of choice in these settings. The purpose of this study is to review the pertinent literature and provide updated information on different laser therapies available for treatment of keloids and hypertrophic scars. A Medline literature search was performed for relevant publications. In this review the results of published studies in the treatment and prevention of hypertrophic scars and keloids are presented. Suggested mechanisms of action are reviewed. A review of the optimal laser parameters to modulate treatment outcome will be discussed. Different lasers are effective in not only the treatment but also the prevention of hypertrophic scars and keloids, among them PDL is more promising. Most of the suggested theories are based on the selective photothermolysis in which the light energy emitted from a vascular laser is absorbed by hemoglobin, generating heat and leading to coagulation necrosis, neocollagenesis, collagen fiber heating with dissociation of disulfide bonds and subsequent collagen fiber realignment. The optimal laser is currently 585 nm PDL, although the recent results of Q-switched 532 nm frequency-doubled Nd:YAG are promising. Early use of lasers are beneficial, especially in those who are prone to develop these lesions.

Intralesional injection with corticosteroid remains the mainstay of therapy for hypertrophic scars and keloids, however some lesions are unresponsive or may result in skin atrophy. Intralesional bleomycin injection is an alternative therapy that has been widely reported. In order to compare the effectiveness and safety of bleomycin for the treatment of keloids and hypertrophic scars in skin of color population, Fitzpatrick skin type III to V patients with keloids or hypertrophic scars were randomized into two groups. Group A was treated monthly with intralesional triamcinolone acetonide (10mg/mL), while group B with intralesional bleomycin (1mg/mL) for three consecutive months. Evaluation of the treatment was performed using "Patient and Observer Scar Assessment Scale" (POSAS), self-rated patient satisfaction score, photography, and ultrasonography. Two patients had their bleomycin blood levels monitored. Twenty-six patients with keloids or hypertrophic scars were recruited. The clinical improvement as assessed by the POSAS was not statistically significant. In terms of patients satisfaction score, one half of both groups reported a very good improvement. Photographic as well as ultrasonographic evaluation showed no difference between the two groups. Bleomycin was found to enter the blood circulation in a very small amount. The major side effect was hyperpigmentation. There was no skin atrophy detected in this study. Intralesional bleomycin is a safe and effective treatment for keloids and hypertrophic scars. The treatment is comparable to intralesional triamcinolone. Unfortunately, hyperpigmentation was the major side effect in darker skin type.