Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis

Jiang, Zhengying; Liao, Xincheng; Liu, Mingzhuo; Fu, Zhonghua; Min, Dinghong; Yu, Xuan; Guo, Guang-hua

doi:10.1007/s00266-020-01721-2

Cited by 23 publications

(11 citation statements)

References 30 publications

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“…In the healthy fibroblast line, folic acid recapitulated many of the abnormalities in keloid fibroblasts while demonstrating opposing effects on metabolism and EMT in the cell line that was keloid derived. These findings are consistent with recent reports demonstrating efficacy for the folate targeting drug 5-FU against keloid scars [41].…”

Section: Discussionsupporting

confidence: 93%

Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3

et al. 2021

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Keloids are a type of disordered scar formation which not only show heterogeneity between individuals and within the scar itself, but also share common features of hyperproliferation, abnormal extra-cellular matrix deposition and degradation, as well as altered expression of the molecular markers of wound healing. Numerous reports have established that cells from keloid scars display Warburg metabolism—a form of JAK2/STAT3-induced metabolic adaptation typical of rapidly dividing cells in which glycolysis becomes the predominant source of ATP over oxidative phosphorylation (OxPhos). Using the JAK1/2 inhibitor ruxolitinib, along with cells from patients with STAT3 loss of function (STA3 LOF; autosomal dominant hyper IgE syndrome) we examined the role of JAK/STAT signaling in the hyperproliferation and metabolic dysregulation seen in keloid fibroblasts. Although ruxolitinib inhibited hyperactivity in the scratch assay in keloid fibroblasts, it paradoxically exacerbated the hyper-glycolytic state, possibly by further limiting OxPhos via alterations in mitochondrial phosphorylated STAT3 (pSTAT3Ser727). In healthy volunteer fibroblasts, folic acid exposure recapitulated the exaggerated closure and hyper-glycolytic state of keloid fibroblasts through JAK1/2- and STAT3-dependent pathways. Although additional studies are needed before extrapolating from a representative cell line to keloids writ large, our results provide novel insights into the metabolic consequences of STAT3 dysfunction, suggest a possible role for folate metabolism in the pathogenesis of keloid scars, and offer in vitro pre-clinical data supporting considerations of clinical trials for ruxolitinib in keloid disorder.

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Section: Discussionsupporting

confidence: 93%

Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3

et al. 2021

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“…For the treatment of keloid scars, it is suggested that 5-FU (maximum 90 mg each injection) + TA treatment resulted in a lower incidence of skin atrophy and telangiectasia than treatment with TA alone (10-40 mg TA single injection)[ 22 , 23 ]. The common dosage range of 5-FU is 45-50 mg/mL, and each injection volume is less than 2 mL, with more than 3 sessions[ 24 ]. In this study, 25 mg 5-FU and 10 mg TA were used intralesionally once for the treatment.…”

Section: Discussionmentioning

confidence: 99%

Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema

Wang¹,

Wang²,

He³

et al. 2022

WJCC

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BACKGROUND Tissue resident memory T (T RM ) cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema. AIM To compare the efficacy and safety of the intralesional injection of 5-fluorouracil (5-FU) and triamcinolone (TA) with those associated with TA alone for the treatment of chronic eczema. METHODS A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only. Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes. All patients were followed up monthly for up to 1 year. RESULTS No serious adverse event was observed in either group. Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment, the relapse rate was significantly lower in the 5-FU+TA group than in the TA group. Histological examination showed significantly fewer CD8 + and CD103 + T cells but not CD4 + T cells in the 5-FU+TA group. CONCLUSION One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of T RM cells in the lesional skin and the relapse rate of chronic eczema.

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“…Also, the effect of combined medication was significantly better than that of 5-FU ( 77 ). In recent years, a meta-analysis also found that TAC combined with 5-FU in the treatment of keloid and hypertrophic scars was more effective and safer than the monotherapy of TAC and 5-FU ( 78 ). The authors further reported that TAC combined with 5-FU was more effective in the treatment of keloid and hypertrophic scars than was intralesional injection TAC.…”

Section: Discussionmentioning

confidence: 99%

Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid

Yang

Luo

2021

Front. Med.

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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.

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Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis

Cited by 23 publications

References 30 publications

Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3

Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3

Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema

Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid

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