Abstract
Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) > TAC+5-FU (69.8%) > BTA (67.3%) > 5-FU+silicone (59.4%) > TAC+silicone (58.3%) > 5-FU (49.8%) > BLM (42.0%) > TAC (26.7%) > VER (26.2%) > silicone (18.3%). There was no publication bias revealed based on the funnel diagram.Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.
Highlights
Pathological scars, including hypertrophic scars and keloids, are mostly caused by the formation of a large extracellular matrix and proliferation of fibroblasts
The former comprised A, triamcinolone acetonide (TAC); B, 5-FU; C, BLM; D, silicone gels; E, botulinum toxin A (BTA); and F, VER. The latter comprised A+B, TAC combined with 5-FU; D+A, silicone gels combined with TAC; D+B, silicone gels combined with 5-FU; and A+E, TAC combined with BTA
Results of Network Meta-Analysis and Publication Bias Results of network meta-analysis (NMA) showed that compared with TAC, only TAC combined with BTA and TAC combined with 5-FU could improve efficacy rate
Summary
Pathological scars, including hypertrophic scars and keloids, are mostly caused by the formation of a large extracellular matrix and proliferation of fibroblasts. Some studies have suggested that the formation of scar may involve a variety of cells like fibroblast, myofibroblast, and mastocyte [5, 6], cytokines like transforming growth factor-β (TGF-β2), and tumor necrosis factor-α [7,8,9], extracellular matrix (deposition of collagen and glycolaminoglycan) [10], and spatial structure of tissue (excessive angiogenesis and repair of the spatial network between cells) [11] Demographic characteristics, such as race, sex, and age, as well as external factors like type of injury, may play a significant role in scar formation [12, 13]. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid
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