Comparison of intralesional verapamil versus intralesional corticosteroids in treatment of keloids and hypertrophic scars: A randomized controlled trial

Background

Keloids and hypertrophic scars are due to overgrowth of dermal collagen following trauma to the skin that usually cause major physical, psychological and cosmetic problems.

The safety and efficacy of intralesional triamcinolone acetonide for keloids and hypertrophic scars: A systematic review and meta-analysis

BackgroundTriamcinolone acetonide (TAC) is widely used for hypertrophic scars and keloids; however, TAC has variable efficacy and safety in different individuals.PurposeTo evaluate the efficacy and safety of intralesional TAC for treatment of hypertrophic scars and keloids.Data sourcesSearches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov prior to 25 March 2020.Study selectionRandomized controlled trials in English that compared TAC with a placebo or other medications that are commonly used for intralesional injection in hypertrophic scars and keloids.Data extractionPrimary outcomes were reduction in scar height, vascularity, pliability, pigmentation, total scores on the Vancouver Scar Scale (VSS) or patient and observer scar assessment scale (POSAS), telangiectasia, and skin atrophy. Secondary outcomes included overall scar improvement.Data synthesisFifteen trials met the inclusion criteria. In the short term, TAC was associated with a significant improvement in vascularity (MD: −0.22, 95% CI: −0.42 to −0.02) and pliability (MD: −0.25, 95% CI: −0.44 to −0.06) compared to verapamil. In the medium term, compared to TAC, 5-FU showed a significant improvement in scar height (SMD: 0.95, 95% CI: 0.15–1.75), while TAC led to a significant improvement in vascularity compared to 5-FU (MD: −0.45, 95% CI: −0.76 to −0.14). Compared to TAC, TAC+5-FU showed a significant improvement in pliability (SMD: 0.98, 95% CI: 0.17–1.78) and pigmentation (MD: 0.45, 95% CI: 0.12–0.78). Botulinum toxin type A resulted in significantly better pliability (SMD: 1.99, 95% CI: 0.98–3.00) compared to TAC. In the long term, compared to TAC, 5-FU led to a significant improvement in scar height (MD: 0.55, 95% CI: 0.17–0.93), but significantly less vascularity (MD: −0.35, 95% CI: −0.65 to −0.05). Compared to TAC, TAC+5-FU produced a significant improvement in scar height (MD: 1.50, 95% CI: 1.12–1.88), pliability (MD: 0.45, 95% CI: 0.10–0.80), and pigmentation (MD: 0.55, 95% CI: 0.24–0.86).ConclusionTAC may be beneficial for the short-term treatment of hypertrophic scars and keloids; however, 5-FU, 5-FU+TAC, and verapamil may produce superior results for medium- and long-term treatments. TAC injections at concentrations of 20 mg/ml or 40 mg/ml are more likely to result in skin atrophy compared to 5-FU or verapamil, and are more likely to cause telangiectasia than 5-FU, 5-FU+TAC, or bleomycin.     

A comparison of the treatment of keloids and hypertrophic scars

Summary The article is a retrospective study of 407 patients having had hypertrophic scars and keloids. The worst 50 cases were treated by excision, kenacort injections during the operation and followed by x-ray therapy within 24 hours. In this latter group 98% of the patients obtained a good or excellent end result.     

Tenascin-C在瘢痕疙瘩和增生性瘢痕中的基因表达研究

目的 探讨Tenascin-C基因在瘢痕疙瘩和增生性瘢痕中的表达。方法 取正常成人皮肤组织RNA，构建正义、反义Tenascin-C(Tn-C)mRNA探针，运用原位杂交技术，观测10例瘢痕疙瘩、10例增生性瘢痕和5例正常成人皮肤组织中Tn-C mRNA的表达。结果 Tn-C mRNA在正常皮肤表皮中无表达，真皮中表达稀少，局限于乳头真皮层的成纤维细胞和皮肤附属器；10例瘢痕疙瘩表皮均有表达，真皮分布较广，如成纤维细胞、血管内皮和皮肤附属器；Tn-C mRNA在3例增生性瘢痕表皮表达，7例无表达，真皮中表达与瘢痕疙瘩相同但较弱，比正常皮肤增多，但差异无显著性。结论 Tenascin-C mRNA在瘢痕疙瘩表皮和真皮中有高表达。     

增生性瘢痕和瘢痕疙瘩裸鼠模型的研制

目的：复制瘢痕动物模型，旨在从形态学和组织学上验证该模型的可靠性，为瘢痕的基础研究开辟一条新途径。方法：将增生性瘢痕和瘢痕疙瘩小组织块分别植入裸鼠皮下，携带一段时间（５～１２０天），且与原瘢痕作光镜和电镜对照。结果：术后裸鼠全部成活。植入物无变性坏死，且无异性细胞浸润，并保持其原有的胶原形态，透射电镜也证实细胞特性保持不变。结论：增生性瘢痕和瘢痕疙瘩植入裸鼠体内能保持其原有的组织学结构特征，裸鼠用作瘢痕动物模型是可行的、可靠的。     

免疫球蛋白在增生性瘢痕及瘢痕疙瘩中的表达

对３５例增生性瘢痕、８例瘢痕疙瘩及７例正常皮肤用免疫组化（ＡＢＣ）法进行免疫球蛋白ＩｇＧ、ＩｇＡ、ＩｇＭ、ＩｇＥ及Ｃ４的分析。本文试图从免疫学方面探讨瘢痕形成有关的免疫性因素。增生性瘢痕及瘢痕疙瘩中ＩｇＧ、ＩｇＡ、ＩｇＭ免疫球蛋白及补体Ｃ４的分布均沿胶原纤维方向沉积，在真皮乳头层血管周围及真皮胶原纤维间，特别在瘢痕结节处，结节内胶原周边较多，在细胞内也有。ＩｇＥ主要沉积在肥大细胞内，染色均较深，量较多。而正常皮肤中ＩｇＡ、ＩｇＧ、ＩｇＥ及Ｃ４也有不同程度沉积，但染色浅淡，数量少。结果表明，在增生性瘢痕、瘢痕疙瘩中免疫球蛋白沉积均比正常皮肤含量多，染色深，增生性瘢痕与瘢痕疙瘩中无明显差异。这些免疫球蛋白可能是ＤＮＡ－抗ＤＮＡ抗体复合物，这些复合物可来自血循环或是损伤后真皮抗核抗体与表皮抗原结合而产生，说明瘢痕的形成和发展与免疫性有关。证实瘢痕发病机理中有局限性免疫反应存在，亦即机体免疫系统在瘢痕发生、发展中具有重要作用     

Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids

There is not much level 1 evidence based literature to guide management of hypertrophic scars and keloids despite an array of therapeutic modalities at disposal. Intralesional (i/l) triamcinolone injections have remained a gold standard in non surgical management. Sporadic reports on use of i/l verapamil suggest its efficacy. Since verapamil has not found sufficient mention as an effective alternative modality, it was decided to undertake a randomized study which could also address some additional clinical parameters.     

瘢痕疙瘩和增生性瘢痕表皮异常的实验研究

目的 探讨瘢痕疙瘩和增生性瘢痕的表皮异常。方法 采用免疫组织化学方法,检测腱糖蛋白C(Tn-C),角蛋白16(CK-16)和增殖相关核抗原Ki-67蛋白在瘢痕疙瘩、增生性瘢痕和正常成人表皮中的表达。取正常成人皮肤组织RNA,构建正义、反义Tn-C mRNA探针,运用原位杂交技术,观测瘢痕疙瘩、增生性瘢痕和正常皮肤表皮中Tn-C mRNA的表达。结果 瘢痕疙瘩、增生性瘢痕表皮角质形成细胞增生明显高于正常皮肤。Tn-C mRNA在瘢痕疙瘩表皮的表达明显高于其在增生性瘢痕及正常皮肤表皮中的表达。CK-16,Ki-67蛋白在瘢痕疙瘩和增生性瘢痕表皮中表达增加。结论 瘢痕疙瘩和增生性瘢痕的表皮存在增生分化异常,尤以瘢痕疙瘩更为明显。     

Role of verapamil in preventing and treating hypertrophic scars and keloids

Keloid and hypertrophic scars are difficult to manage and remain a therapeutic challenge. Verapamil has shown a great potential in the management of keloid and hypertrophic scars. Comparing with conventional corticosteroid injections, verapamil could improve the appearance of keloid and hypertrophic scars, and is associated with a lower incidence of adverse effects. Is verapamil an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars? The aim of this study was to assess the effectiveness of verapamil in preventing and treating keloid and hypertrophic scars. Searches were conducted in Medline, EMbase and Cochrane databases from 1974 to January 2015. The selection of articles was limited to human subjects. Five randomised controlled trials (RCTs) or cluster‐randomised trials or controlled clinical trials (CCTs) comparing the efficacy of verapamil with conventional treatments were identified. The results showed that verapamil could improve keloid and hypertrophic scars, and was not significantly different from conventional corticosteroid injections. Few adverse effects were observed. However, this result should be considered carefully, as most of the included studies have a high risk of bias because of issues with randomization, allocation concealment, blinding, incomplete outcomes and selective reporting. In conclusion, verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. More high‐quality, multiple‐centre, large‐sample (RCTs) are required to define the role of verapamil in preventing and treating keloid and hypertrophic scars.     

Efficacy and safety of triamcinolone acetonide alone and in combination with 5‐fluorouracil for treating hypertrophic scars and keloids: a systematic review and meta‐analysis

Pathological scars, such as keloids and hypertrophic scars, readily cause physical and psychological problems. Combination 5‐fluorouracil (5‐FU) with triamcinolone acetonide (TAC) is presumed to enhance the treatment of pathological scars, although supportive evidence is lacking. We aimed to compare the efficacy and safety of TAC alone and in combination with 5‐FU for the treatment of hypertrophic scars and keloids. Five databases (PubMed, Medline, Cochrane databases, Embase and CNKI) were searched with the limitations of human subjects and English‐language text. Mean differences (MDs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Cochrane Collaboration''s Risk of Bias Tool was used to assess the risk of bias. The control group received intralesional TAC alone, and the experimental group received TAC combined with 5‐FU injection. A pooled analysis of the effectiveness based on patient self‐assessment after treatment showed that the experimental group achieved better results than the control group (OR = 2·92, 95% CI = 1·63–5·22, P = 0·0003). Similarly, a pooled analysis of the effectiveness based on observer assessment following treatment produced the same conclusion (OR = 4·03, 95% CI = 1·40–11·61, P = 0·010). A meta‐analysis of scar height after treatment showed that the experimental group performed better than the control group (MD = −0·14, 95% CI = −0·23–0·05, P = 0·002). The erythema score of the experimental group after treatment was superior (MD = −0·20, 95% CI = −0·34–0·06, P = 0·004). The heterogeneity test showed no heterogeneity among the studies (P > 0·1, I ² = 0%). TAC combined with 5‐FU is more suitable for the treatment and prevention of hypertrophic scars and keloids, with greater improvement in scar height and patient satisfaction as well as fewer side effects.     

The efficacy of excision followed by intralesional 5-fluorouracil and triamcinolone acetonide versus excision followed by radiotherapy in the treatment of ear keloids: A randomized control trial

Background

The ear is the common site for keloid formation especially in women after ear piercing. Surgery is the main stay of treatment in these lesions but there are large numbers of treatment failures in surgery alone.

Combination therapy using non‐ablative fractional laser and intralesional triamcinolone injection for hypertrophic scars and keloids treatment

Combinations of various treatment modalities were shown to be more effective than monotherapy when treating hypertrophic scars and keloids. This study was conducted to assess the effectiveness of combination therapy with non‐ablative fractional laser and intralesional steroid injection. From May 2015 to June 2017, a total of 38 patients with hypertrophic scars or keloids were evaluated. The control group of 21 patients received steroid injection alone, and 17 patients (the combined group) received 1550‐nm erbium‐glass fractional laser treatment and steroid injection simultaneously. The mean number of treatment sessions was statistically fewer in the combined group than in the control group (6.95 vs 5.47, P = .042). There was a significant difference in the patient's scale in the combined group (14.62 vs 22.82, P = .005); however, the observer's scale was not significantly different (17.92 vs 20.55, P = .549). The recurrence rate was 38.1% (8/21) in the control group and 35.3% (6/17) in the combined groups and showed no significant difference (P = .859). However, the mean remission period was statistically longer in the combined group (3.00 months vs 4.17 months, P = .042). Combination therapy with non‐ablative fractional laser and intralesional steroid injection showed better results for the treatment of hypertrophic scars and keloids with fewer treatment sessions, better patient satisfaction, and longer remission periods.     

病理性瘢痕中原癌基因c-myc和c-fos的表达

目的　探讨原癌基因的表达与病理性瘢痕形成的相关性。方法　应用免疫组化SP法 ,检测c -myc和c -fos蛋白在增生性瘢痕、瘢痕疙瘩和正常皮肤组织中的表达和分布 ,并用图像定量分析比较其差异。结果　在增生性瘢痕和瘢痕疙瘩的成纤维细胞中c-myc、c -fos呈强阳性表达 ,两组间无明显差异 ,而与正常皮肤对照组均有显著性差异。结论　增生性瘢痕与瘢痕疙瘩中c -myc、c -fos蛋白表达升高 ,存在c -myc和c -fos原癌基因的激活 ,可能参与了成纤维细胞的分化增殖或表型转化、胶原合成与降解以及对细胞因子的调控 ,并导致瘢痕增生。     

病理性瘢痕中c-fos原癌基因的表达

目的　病理性瘢痕是创伤过度愈合的结果,以成纤维细胞的异常增殖、合成及分泌大量胶原和细胞外基质为特征,其形成机理仍不清楚。探讨原癌基因c-fos的表达与病理性瘢痕形成的相关性。方法　应用免疫组化SP法,检测c-fos蛋白在增生性瘢痕、瘢痕疙瘩及正常皮肤组织中的表达和分布,并用图像定量分析比较其差异。结果　在增生性瘢痕和瘢痕疙瘩的成纤维细胞中c-fos呈强阳性表达,两组间无明显差异,而与正常皮肤对照组均有显著性差异。结论　增生性瘢痕与瘢痕疙瘩中c-fos蛋白表达升高,存在c-fos癌基因的激活,可能参与了成纤维细胞的分化增殖、胶原合成与降解以及对细胞因子的调控,并导致瘢痕增生。     

病理性瘢痕中c-fos原癌基因的表达

目的　病理性瘢痕是创伤过度愈合的结果 ,以成纤维细胞的异常增殖、合成及分泌大量胶原和细胞外基质为特征 ,其形成机理仍不清楚。探讨原癌基因c -fos的表达与病理性瘢痕形成的相关性。方法　应用免疫组化SP法 ,检测c -fos蛋白在增生性瘢痕、瘢痕疙瘩及正常皮肤组织中的表达和分布 ,并用图像定量分析比较其差异。结果　在增生性瘢痕和瘢痕疙瘩的成纤维细胞中c-fos呈强阳性表达 ,两组间无明显差异 ,而与正常皮肤对照组均有显著性差异。结论　增生性瘢痕与瘢痕疙瘩中c -fos蛋白表达升高 ,存在c -fos癌基因的激活 ,可能参与了成纤维细胞的分化增殖、胶原合成与降解以及对细胞因子的调控 ,并导致瘢痕增生     

低浓度5-氟尿嘧啶抑制血管增生在瘢痕疙瘩综合治疗中的作用初探

目的 探讨低浓度5-氟尿嘧啶（5-FU）抑制血管增生在瘢痕疙瘩临床综合治疗中的作用。方法 35名瘢痕疙瘩患者，共51个瘢痕疙瘩。平均病史9．7年。以5-Fu2～5mg／ml瘢痕内注射，1次／2周。3～6次后辅以糖皮质激素注射。平均治疗时间为10．29个月。结果 低浓度5-FU抑制瘢痕疙瘩血管增生有效率为96．77％；在治疗6个月以上的患者中，5-FU结合糖皮质激素治疗瘢痕疙瘩的总有效率为97．14％，其中完全缓解者占45．71％，极大缓解者占48．57％，部分缓解者占2．86％．未缓解者占2．86％。结论 利用低浓度5-FU抑制血管增生的作用结合糖皮质激素治疗瘢痕疙瘩具有良好的疗效。     

A protocol for the treatment of hypertrophic scars and keloids

Hypertrophic scars and keloids still present problems in both white and pigmented skin. A treatment protocol is proposed: Hypertrophic scars are primarily treated with intralesional injections of corticosteroids or with compression therapy. Surgical scar revision is only secondarily indicated. Recurrent and resistant hypertrophic scars are surgically excised and postoperatively irradiated (twice with 400-cGy 7-MeV electron irradiation).Presented at the VIII Congress of the International Society of Aesthetic Plastic Surgery, Madrid, Spain, 16 September 1985     

去炎松-A和5-氟脲嘧啶混合液对增生性瘢痕胶原代谢影响的实验研究

目的　探讨TAC和 5 -FU混合液对增生性瘢痕胶原代谢的影响。方法　用兔耳建立增生性瘢痕动物模型 ,随机分成四组 ,在瘢痕局部注射TAC和 5 -FU混合液为A组、注射TAC为B组、注射 5 -FU为C组、对照为D组 ,每周注射 1次 ,第 4次注射后 1周观察组织学改变 ,测定瘢痕内HPr、PCⅢ的含量 ,Ⅰ、Ⅲ型胶原面积及比例。结果　①组织学 :D组呈现出增生性瘢痕的病理特征 ,A、B、C三组呈现胶原纤维溶解 ,成纤维细胞的超微结构受到明显影响。②HPr和PCⅢ含量测定 :A、B、C、D四组之间比较差异有显著意义 (P <0 .0 5 ) ,A组含量最低 ,D组含量最高。③Ⅰ、Ⅲ型胶原面积及比例测定 :A、B、C、D四组Ⅰ、Ⅲ型胶原面积差异有显著意义 (P <0 .0 5 ) ,A组Ⅰ型胶原比例最低。结论　TAC和 5 -FU混合液能有效抑制增生性瘢痕内胶原的合成 ,降解胶原纤维 ,对Ⅰ型胶原的抑制比Ⅲ型胶原强 ,改善Ⅰ、Ⅲ型胶原的构成比 ,作用强于单纯的应用TAC或 5 -FU。