Studies of transforming growth factors beta 1-3 and their receptors I and II in fibroblast of keloids and hypertrophic scars

Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterized by an abnormal deposition of extracellular matrix components, particularly collagen. There is uncertain evidence that transforming growth factor-beta (TGFss) is involved in keloid formation. Therefore we investigated the expression of TGFss1, 2 and 3 and their receptors in keloids, hypertrophic scars and normal skin. Dermal fibroblasts were obtained from punch biopsies of patients with keloids and hypertrophic scars and from normal skin of healthy individuals. Total RNA was isolated and the expression of TGFss1, 2 and 3 and of TGFss receptors I and II (TGFssRI and II) was analysed by real-time PCR using the Lightcycler technique. Our data demonstrate significantly lower TGFss2 mRNA expression in hypertrophic scar fibroblasts as compared with fibroblasts derived from keloids and normal skin (p<0.05). In contrast, TGFss3 mRNA expression was significantly lower in keloid fibroblasts in comparison with fibroblasts derived from hypertrophic scar and normal skin (p<0.01). TGFssRI mRNA expression was significantly decreased in hypertrophic scar fibroblasts (p<0.01) and TGFssRII mRNA expression was decreased in keloids compared with hypertrophic scar fibroblasts (p<0.001). The ratio of TGFssRI/TGFssRII expression was increased in keloids compared with hypertrophic scar and normal skin fibroblasts. As recently supposed, an increased TGFssRI/TGFssRII ratio could promote fibrosis. Therefore our data support a possible role of TGFssRI and TGFssRII in combination with a certain TGFss expression pattern as fibrosis-inducing factors in keloids.     

Treatment of keloids and hypertrophic scars

Clinicians always find it difficult to treat hypertrophic scars and keloids. Various treatment modalities are available. Intralesional corticosteroids, topical applications, cryotherapy, surgery, laser therapy, and silicone sheeting are the widely used options. Radiation therapy can also help in cases of recalcitrant keloids. Most recently, pulsed-dye laser has been successfully used to treat keloids and hypertrophic scars. There are no set guidelines for the treatment of keloids. Treatment has to be individualized depending upon the distribution, size, thickness, and consistency of the lesions and association of inflammation. A combination approach to therapy seems to be the best option.     

Enzyme activity in human scars, hypertrophic scars and keloids

Biopsies from non-hypertrophic and hypertrophic scars and from normal skin have been studied histochemically for activities of nicotanamide adenine dinucleotide diaphorase, lactate dehydrogenase, acid phosphatase, beta-D glucuronidase and alkaline phosphatase. The activities of all enzymes studied except alkaline phosphatase were found to be increased in hypertrophic scars as compared with non-hypertrophic scars and normal skin.     

Laser treatment of keloids and hypertrophic scars

BACKGROUND: 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. OBJECTIVES: 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. METHODS: A Medline literature search was performed for relevant publications. RESULTS: 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. CONCLUSION: 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.     

Cryosurgical treatment of hypertrophic scars and keloids

The treatment of hypertrophic scars and keloids is a problem that has not yet been satisfactorily solved. We report here the results obtained with cryosurgery by the contact freezing method in 45 patients with 56 evaluated lesions. During the period of the investigation, cryosurgical treatment was completed in 23 patients with 28 lesions: in 53.6% we recorded an excellent result (ER), in 32.1% a good result, and in 14.7% a poor result. None of the lesions was totally resistant. Lesions that had been present for under 1 year (ER = 77.8%) and hypertrophic scars (ER = 72.2%) responded better than older lesions (ER = 41.2%) and keloids (ER = 20.0%), respectively. Optimal results were obtained after 4 +/- 2 sessions. Evaluation of the cryosurgical treatment in all patients revealed that the flattening of the lesions was increased after each session. Hypertrophic scars and lesions less than 4 cm2 in area responded more quickly than keloids and larger lesions, respectively. Pretreatment had a negative influence on the results of cryosurgery. No relapses were observed. The treatment was generally well tolerated, slight pain during freezing (52.1%) and hypo-/hyperpigmentation (22.9%) being the most frequent side-effects. Cryosurgery is simple to learn, and the technique is recommended for the treatment of hypertrophic scars and keloids.     

Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions

The extracellular matrix (ECM) environment in connective tissues provides fibroblasts with a structural scaffold and modulates cell shape, but it also profoundly influences the fibroblast phenotype. Here we studied fibroblasts cultured in a three-dimensional network of native collagen, which was either mechanically stressed or relaxed. Mechanical load induces fibroblasts that synthesize abundant ECM and a characteristic array of cytokines/chemokines. This phenotype is reminiscent of late granulation tissue or scleroderma fibroblasts. By contrast, relaxed fibroblasts are characterized by induction of proteases and a subset of cytokines that does not overlap with that of mechanically stimulated cells. Thus, the biochemical composition and physical nature of the ECM exert powerful control over the phenotypes of fibroblasts, ranging from "synthetic" to "inflammatory" phenotypes. Interactions between fibroblasts and collagen fibrils are mostly mediated by a subset of beta 1 integrin receptors. Fibroblasts utilize alpha 1 beta 1, alpha 2 beta 1, and alpha 11 beta 1 integrins for establishing collagen contacts and transducing signals. In vitro assays and mouse genetics have demonstrated individual tasks served by each receptor, but also functional redundancy. Unraveling the integrated functions of fibroblasts, collagen integrin receptors, collagen fibrils, and mechanical tension will be important to understand the molecular mechanisms underlying tissue repair and fibrosis.     

Treatment of keloids and hypertrophic scars using bleom

Background Numerous treatments have been attempted with unsatisfactory results using either single or combination modalities for treatment of keloids and hypertrophic scars. The aim of our study was to determine the effectiveness and safety of bleomycin in the treatment of hypertrophic scars and keloids. Methods This study included 50 patients with keloids and hypertrophic scars. Bleomycin was administered through multiple superficial puncture technique. Three applications were given at intervals of 15 days each, followed by a fourth and final application 2 months after the last application. Final results were read 2 months after the last application.

Postoperative prevention of hypertrophic scars and keloids using radiotherapy

A group of 63 patients with keloids or hypertrophic scars were treated with excision and postoperative superficial X-ray irradiation. The cosmetic and functional results were very good in more than two-thirds of these cases. In 10% a relapse occurred, which is in keeping with the international literature. Finally, other radiotherapeutic modalities such as brachytherapy, in combination with hyperthermia are discussed.     

Topical tamoxifen therapy in hypertrophic scars or keloids in burns

As acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-β₁. The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-β₁, with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice.     

Studies on the immunologic aspects of keloids and hypertrophic scars

Summary A significant difference between keloids and hypertrophic scars could be demonstrated by means of acid elution of lymphoid blood cells and immunofluorescence studies. A total of 20 patients (13 patients with keloids and seven with hypertrophic scars) were investigated.All the 13 patients with keloids revealed in the eluates antinuclear antibodies belonging to one or more of the five main classes and directed mainly against fibroblasts. On the other hand, there were no antinuclear antibodies detectable in the eluates of the seven patients with hypertrophic scars and in over 40 healthy controls.     

Laser treatment of hypertrophic scars, keloids, and striae

The successful use of the 585-nm pulsed dye laser for the treatment of hypertrophic scars has been well established over the past decade. Although 5 years ago this treatment option might have been considered as a viable choice only after all other methods failed, it is now generally recognized as an excellent first-line treatment option. Early scar treatment with pulsed dye laser irradiation effectively prevents scar formation or worsening and yields a better and more prolonged clinical improvement. The concomitant use of corticosteroids, 5-fluorouracil, or other treatments is proving to be of particular importance in reducing scar bulk and symptoms of more proliferative scars. Although optimal management for keloids and striae has yet to be determined, pulsed dye laser irradiation will no doubt continue to play a role in their treatment.     

Recommendations for the prevention and therapy of hypertrophic scars and keloids

Hypertrophic scars and keloids form due to aberrations in the physiologic wound healing cascade characterized by greater and more sustained ECM deposition. Both entities are frequently associated with pain, pruritus and contractures, and are thus significantly affecting the patient??s quality of life. Genetic susceptibility, specific anatomic locations, prolonged inflammation and delayed epithelialization significantly contribute to excessive scar formation. However, despite intensive scientific work in this field the complex mechanisms underlying the processes of scarring and wound contraction remain poorly understood and most therapeutic approaches are clinically unsatisfactory. Nevertheless, based on a rising number of clinical studies next to well-known therapeutic concepts including cryotherapy and intralesional triamcinolone, recent techniques extend the spectrum for treating excessive scars. Nonetheless, prevention of pathologic scarring is undoubtedly more effective than to later attempts to treat it.     

Treatment of keloids and hypertrophic scars using topical and intralesional mitomycin C

Background Keloids develop due to the overgrowth of fibrous tissue. Currently, there is no gold standard treatment for keloids and hypertrophic scars (HTS). Their propensity for local invasion and recurrence has prompted many investigations on antineoplastic agents. Objectives To investigate the efficacy of topical and intralesional mitomycin C for the treatment of keloids and HTS. Methods Nine patients with clinically diagnosed keloids and HTS were treated using topical mitomycin C (1 mg/mL) for 3 min after shaving excision. The Vancouver Scars Scale, patient satisfaction, and adverse effects were checked after 6 months. The keloids and HTS were photographed at each monthly visit. Intralesional mitomycin C (1 mg/mL) was administered to study the effect on the regression of keloids in 2 patients. Results Application of mitomycin C to the base of shave‐removed keloids and HTS showed good results. Six out of 9 patients were very satisfied with the outcome of treatment; none were disappointed. The results of intralesional mitomycin C treatment were disappointing. Both cases worsened, with increased ulceration after treatment. Conclusions Topical application of mitomycin C following shaving excision was safe and effective for the treatment of keloids and HTS. However, intralesional mitomycin C therapy aggravated both lesions.     

康瑞保凝胶治疗肥厚性瘢痕和瘢痕疙塔临床观察

评价康瑞保凝胶治疗肥厚性瘢痕和 瘢痕疙瘩的有效性和安全性。75例肥厚性瘢痕和瘢痕疙瘩使用 康瑞保凝胶,每日3次,连续6个月。结果 治愈率9.3％,显效率50367%,总有效率59.97%,此药无明显不良反应。     

The local treatment of hypertrophic scars and keloids with topical retinoic acid

In a clinical trial twenty-eight intractable cases with scars were treated with daily applications of a 0.05% solution of retinoic acid. The results were evaluated objectively and subjectively. Slight to marked reduction of the size of these scars and decrease of such complaints as itching were noted in the majority of the cases. A favourable result was obtained according to the patients in 79%, and according to the opinion of the medical examiner in 77% of the patients.     

32P-patch contact brachyradiotherapy in the management of recalcitrant keloids and hypertrophic scars

Keloids are the result of excessive fibroblast proliferation and then over-abundant collagen deposition. There is no method able to guarantee absolute success in the therapeutic approach to keloids. Our case report involves a female patient with six lesions treated with a 32P-patch brachyradiotherapy. Pre-treatment and adjuvant treatment of the lesions were performed with thiomucase, 5-fluoruracil, procaine and triamcinolone. Taking into account the activity contained in each of the patches and the total radiation dose to be administered according to clinical practice, dosimetric calculations were done for each lesion. Separate silicone patches with chromic [32P]phosphate were designed for each lesion based on these calculations. Total remission was achieved in three treated lesions. The other lesions did not achieve total remission yet, but their sizes are diminishing. The differences observed in treatment outcome may be related with lesion features, adjuvant treatments and/or treatment schedule.