Evidence of invasive and noninvasive treatment modalities for hypertrophic scars: A systematic review

Abstract

Currently, there are various therapeutic approaches to reduce hypertrophic scarring; however, there is no standard evidence-based treatment protocol. Hence, a systematic review was performed to obtain a summary of the latest clinical trials to evaluate evidence for the treatment of hypertrophic scars. The review protocol was registered and approved by PROSPERO (CRD42015027040). PubMed and Web of Science were searched using predefined MeSH-Terms to identify studies published within the last 10 years regarding treatment for hypertrophic scars. Exclusion criteria included a level of evidence (LoE) lower than I, nonhuman in vivo studies, in vitro studies, studies on keloids, literature reviews, and non-English articles. The literature search identified 1,029 unique articles, whereas 6 articles were prospective, randomized, blinded, controlled clinical trials with a LoE I, and were thus included in the systematic analysis. Three clinical trials evaluated silicone products and pressure garments, and the other three studies investigated the efficacy of intralesional injections of triamcinolone (TAC), 5-Fluorouracil (5-FU) combined with TAC as well as the additional irradiation with a 585 nm pulsed-dye laser (PDL). Intralesional injections revealed significant improvements of the scar quality in terms of height, thickness, erythema, and pigmentation. Pressure garments showed favorable results but there was no evidence that silicone products were able to improve the scar quality. The systematic review demonstrated that there are just a few clinical trials with a LoE of I. Consequently, evidence is still lacking especially for noninvasive treatment regimens for hypertrophic scars. Intralesional injections of 5-FU mixed with a low dose of TAC can be seen as most appropriate treatment modality. Prospective clinical trials to determine the efficiency of silicone products are warranted.

Evidence‐based therapy in hypertrophic scars: An update of a systematic review

“…A systematic review of the literature has been conducted. The methods resembled those used in this previous study, 36 which have been approved and registered on the International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42015027040 38…”

“…Second, titles, abstracts and if not unambiguous, full‐text articles have been analyzed concerning the exact study purpose. Again, the same exclusion criteria have been applied as in Reference 36, with the following exclusion reasons: 0 = non‐English, 1 = wrong topic, 2 = in vitro/ex vivo study, 3 = animal study, 4 = keloid study, 5 = review article, 6 = prevention of hypertrophic scars.…”

“…Mustoe et al suggest “ a move to a more evidence‐based approach in scar management ”, already in 2002 34 . Ogawa in 2010 35 and Kafka et al in 2017 36 conclude similarly that there is an urgent need for high‐quality trials to properly evaluate the effectiveness of the treatment modalities available. Additionally, the nonstandardized evaluation methods and study protocols in between different trials, have, to the authors' knowledge, so far prevented researchers from meta‐analyzing the available studies.…”

Use of 5-Fluorouracil for Management of the Thick-Skinned Nose

“…9 Numerous case series and randomized controlled trials have demonstrated excellent safety and efficacy of 5-FU alone and in combination with steroids for the treatment of keloids and hypertrophic scars. [10][11][12][13][14][15][16][17][18][19][20][21][22] The drug's inhibition of TGF-beta is believed to be responsible for its activity on keloid and hypertrophic scars, both of which are characterized by the abnormal organization of collagen fibers. 23 5-FU is effective for both treatment and prevention of exuberant scarring and treatment response is improved when scars are newer.…”

Single cell sequencing identifies serine proteases as regulators of myofibroblast differentiation

“…Topical silicone application, compression or massage therapy, laser ablation, surgery, and intralesional injection of triamcinolone (TAC), corticosteroids, or 5-Fluorouracil are the most commonly used options for prevention or treatment of hypertrophic scars 6,9,10,11 . However, many of these therapies lack evidence of efficacy and safety, and mechanisms of actions are still unclear 10,12 .…”