Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation

IF 2.2 3区医学 Q2 DERMATOLOGY

Lasers in Surgery and Medicine Pub Date : 2024-01-15 DOI:10.1002/lsm.23754

Esteban A. Molina MS, Taryn E. Travis MD, Lou'ay Hussein BS, Mary A. Oliver BS, John W. Keyloun MD, Lauren T. Moffatt PhD, Jeffrey W. Shupp MD, Bonnie C. Carney PhD

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引用次数: 0

Abstract

Objectives

Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls.

Methodology

Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO₂ laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Šídák's multiple comparisons test was used to compare groups.

Results

Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the −Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (−Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (−Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment.

Conclusion

Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

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用短期外用他克莫司治疗色素沉着的烧伤增生性疤痕不会导致色素再沉着。

目的：色素沉着症是增生性瘢痕（HTS）中未被充分研究的一个方面。通过促进黑色素生成和黑色素细胞增殖，外用他克莫司已成功地使白癜风患者的皮肤恢复色素。我们假设，与对照组相比，使用局部他克莫司治疗的 HTS 会增加再色素沉着：方法：对红色杜洛克猪的全厚烧伤进行切除和网状分层植皮或切除和不植皮处理，这些伤口形成了色素沉着的HTS（n = 8）。其中一半的疤痕涂上 0.1% 他克莫司软膏，每天两次，持续 21 天，而对照组则不做任何处理。此外，在局部使用他克莫司诱导激光辅助给药（LADD）之前，将每个疤痕一分为二，一半疤痕接受二氧化碳激光点阵消融治疗。在第 0 天（治疗前）、第 7 天、第 14 天和第 21 天，使用无创探针测量黑色素指数（MI），评估色素沉着情况。在每个时间点，取冲孔活检组织，用福尔马林固定或用分散酶培养。福尔马林固定的活检组织用于通过 H&E 染色评估黑色素水平。在分散酶中培养的活组织用于获取表皮片。然后闪速冷冻 ES，从中分离出 RNA，用于黑色素生成相关基因的定量反转录聚合酶链反应：酪氨酸酶（TYR）、TYR 相关蛋白-1（TYRP1）和多巴醌合成酶（DCT）。结果表明，随着时间的推移，嫁接的 H 细胞内的酪氨酸酶和多巴醌同工酶的数量都在增加，而酪氨酸酶和多巴醌同工酶的数量则在减少：结果：随着时间的推移，在移植的 HTS 和 NS 组中，除 -Tacro 组第 3 周外，MI 没有显著变化。(+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5)。随着时间的推移，未移植 HTS 组和 NS 组的 MI 没有显著变化。(+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3)。与非 LADD 组相比，LADD 并未导致色素沉着的任何不同变化。在任何时间点，组织打孔活检中都没有黑色素生成增加的证据。治疗后，TYR、TYRP1或DCT基因表达没有变化：结论：使用 0.1% 他克莫司软膏或不使用 LADD 治疗色素减退的 HTS，其再色素沉着并没有明显增加。这项研究的局限性在于，治疗间隔时间比已知的白癜风患者色素恢复所需的时间短。使用非侵入性的局部治疗方法来促进色素恢复，是缓解烧伤疤痕色素沉着症相关发病率的一种有吸引力的策略，需要进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lasers in Surgery and Medicine 医学-外科

CiteScore

5.40

自引率

12.50%

发文量

119

审稿时长

1 months

期刊介绍： Lasers in Surgery and Medicine publishes the highest quality research and clinical manuscripts in areas relating to the use of lasers in medicine and biology. The journal publishes basic and clinical studies on the therapeutic and diagnostic use of lasers in all the surgical and medical specialties. Contributions regarding clinical trials, new therapeutic techniques or instrumentation, laser biophysics and bioengineering, photobiology and photochemistry, outcomes research, cost-effectiveness, and other aspects of biomedicine are welcome. Using a process of rigorous yet rapid review of submitted manuscripts, findings of high scientific and medical interest are published with a minimum delay.