Alterations in fibroblast alpha1beta1 integrin collagen receptor expression in keloids and hypertrophic scars

Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by excess collagen. Although extensive research has focused on fibroblasts and collagen turnover in these aberrant scars, little work has been done on the expression of integrins (cell membrane structures that link cells to extracellular matrix) within these lesions. Integrin-mediated regulation of collagen synthesis has previously been observed in explanted fibroblasts from normal and fibrotic dermis, and integrin alpha1 knockout mice maintain increased collagen synthesis consistent with a role for alpha1beta1 in providing negative feedback on collagen synthesis. These findings suggested the need to evaluate integrin roles in keloids and hypertrophic scars. In this study we examined integrin expression in keloids (n = 11), hypertrophic scars (n = 5), radiation ulcers (n = 2), and normal skin specimens (n = 8). We used a novel approach to analysis by isolating dermal fibroblasts directly from tissue (without explant culture) and determining surface integrin expression by flow cytometry. We found that keloids and hypertrophic scars have marked alterations in fibroblast integrin expression and contain several distinct populations of fibroblasts. One of these populations expresses high levels of alpha1 integrin, and the proportion of these cells is higher in keloids (63% +/- 3.6% SEM) and hypertrophic scars (45% +/- 2.7% SEM) than in normal skin tissues (28% +/- 4.7% SEM). The different populations of fibroblasts defined by integrin expression merge, however, when the cells are serially cultured, suggesting that there may be aspects of the dermal microenvironment that maintain the integrin phenotypic heterogeneity in dermal fibroblasts.     

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.     

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.     

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.     

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.     

Expression of mast cell growth modulating and chemotactic factors and their receptors in human cutaneous scars

In order to explore possible mechanisms involved in the previously documented turnover of mast cell subpopulations in human cutaneous scars, we have examined selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF, NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were significantly increased in the epidermis and throughout the dermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF-p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF expression was in contrast scarce and weak, with no differences between normal skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II, and both NGF-receptors, but not GM-CSFR, were significantly increased as well. TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were identified on 70% and 73%, respectively, of avidin-positive normal mast cells on double immunofluorescence microscopy. As described before for the SCF receptor KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin-positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orchestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of their receptors.