馬少吟 朱慧蘭
·綜述·
點(diǎn)陣激光的臨床應(yīng)用進(jìn)展
馬少吟 朱慧蘭
由于點(diǎn)陣激光具有療效肯定,安全性高和停工期短等優(yōu)點(diǎn),已成功用于治療痤瘡瘢痕和光老化等。與傳統(tǒng)的剝脫性和非剝脫性激光不同,點(diǎn)陣激光僅作用部分皮膚,保留周?chē)Fつw,從而有利于快速愈合和減少停工期。點(diǎn)陣激光通過(guò)微治療孔傳遞高能量到達(dá)真皮層,從而保證療效,而避免傳統(tǒng)剝脫性激光容易出現(xiàn)的風(fēng)險(xiǎn)為持續(xù)性色素減退和瘢痕。概述近幾年剝脫性和非剝脫性點(diǎn)陣激光在瘢痕、光老化、萎縮紋、色素性疾病、脫發(fā)和點(diǎn)陣激光經(jīng)皮給藥等的臨床應(yīng)用、機(jī)制和療效。
激光療法;瘢痕;細(xì)胞衰老;投藥,皮膚;點(diǎn)陣激光
1.1 痤瘡瘢痕:萎縮性痤瘡瘢痕是由于損傷修復(fù)過(guò)程中膠原的合成受抑制而形成,組織學(xué)顯示,真皮厚度變薄和毛囊皮脂腺單位數(shù)量減少。激光氣化表皮層,通過(guò)表皮的再生、修復(fù)和真皮熱損傷刺激膠原,角質(zhì)形成細(xì)胞能分泌各種細(xì)胞因子刺激膠原的合成,從而改善臨床癥狀[1]。點(diǎn)陣激光(尤剝脫性點(diǎn)陣激光)治療萎縮性痤瘡瘢痕取得良好療效。高能量密度的點(diǎn)陣激光能加熱至真皮層,較好地刺激膠原重排和合成。不同波長(zhǎng)的點(diǎn)陣激光改善痤瘡瘢痕的療效和不良反應(yīng)發(fā)生率不同,點(diǎn)陣CO2激光輸出有深和小光點(diǎn)的Deep FX模式有利于剝脫、凝固,用于治療瘢痕不平整部位和凹陷區(qū),而作用淺而大光點(diǎn)的ActiveFX模式有利于改善紋理和色素,44例中國(guó)痤瘡患者接受2個(gè)療程的點(diǎn)陣CO2激光治療,每個(gè)療程先用DeepFX治療瘢痕部位,再用ActiveFX模式對(duì)整臉治療一遍,2個(gè)療程間隔為2~6個(gè)月。64%(28/44)的患者治療后改善率為51% ~75%,3例改善率 >75%,但術(shù)后出現(xiàn)炎癥后色素沉著(PIH)的概率達(dá) 50%[2]。
點(diǎn)陣Er:YAG激光作用皮膚凝固深度僅為點(diǎn)陣CO2激光的1/3,通過(guò)自身對(duì)比兩種激光改善痤瘡瘢痕的療效,點(diǎn)陣Er:YAG激光側(cè)(55%)和點(diǎn)陣CO2激光治療側(cè)(65%)取得>50%的療效,但差異無(wú)統(tǒng)計(jì)學(xué)意義。臨床選擇治療的方案不僅考慮其療效,還應(yīng)考慮其不良反應(yīng)、停工期和治療時(shí)疼痛感。點(diǎn)陣CO2激光治療時(shí)疼痛感明顯,出現(xiàn)的炎癥后色素沉著(PIH)傾向性更高,故 Manuskiatti等[3]認(rèn)為,亞洲患者選擇點(diǎn)陣Er:YAG激光改善痤瘡瘢痕更好。
Cho等[4]比較1 550 nm非剝脫點(diǎn)陣激光和點(diǎn)陣CO2激光改善痤瘡瘢痕的療效,治療后3個(gè)月非剝脫點(diǎn)陣激光改善程度不如點(diǎn)陣CO2激光,而非剝脫點(diǎn)陣激光脫痂、術(shù)后紅斑持續(xù)時(shí)間(2.3 d和7.5 d)和疼痛指數(shù)(3.9±2.0)明顯短于點(diǎn)陣CO2激光(7.4 d和 11.5 d,7.0 ± 2.0)。Alajlan 和 Alsuwaidan[5]對(duì)比1 550 nm非剝脫點(diǎn)陣激光和剝脫點(diǎn)陣CO2激光的療效,兩種點(diǎn)陣激光均可治療痤瘡瘢痕,患者滿意度高,而1 550 nm激光術(shù)后出現(xiàn)的PIH(17%)反而高于點(diǎn)陣CO2激光(14%),呈黃褐斑樣的改變。
不同類(lèi)型痤瘡瘢痕點(diǎn)陣激光治療后療效不同,冰錐型痤瘡瘢痕療效較差,而碾壓型或淺貨車(chē)型療效較前者好,采用點(diǎn)陣CO2激光DeepFX聯(lián)合ActiveFX 模式療效更佳[2]。
1.2 外傷性瘢痕和燒傷性瘢痕:點(diǎn)陣CO2激光能改善燒傷性瘢痕,尤其是成熟穩(wěn)定的瘢痕,其作用機(jī)制可能與治療后Ⅰ/Ⅲ型原膠原mRNA下調(diào),Ⅰ/Ⅲ型原膠原mRNA的比例發(fā)生改變,治療后基質(zhì)金屬蛋白酶1的表達(dá)增加,轉(zhuǎn)化生長(zhǎng)因子β2、β3和 堿性成纖維細(xì)胞生長(zhǎng)因子水平明顯下調(diào)有關(guān)[6]。Kim等[7]比較點(diǎn)陣CO2激光與585 nm脈沖染料激光改善手術(shù)瘢痕的療效,結(jié)果顯示,點(diǎn)陣CO2激光對(duì)于改善外傷瘢痕的柔韌性和厚度具有優(yōu)勢(shì),而脈沖染料激光則在改善瘢痕的血管形成和色素方面更勝一籌。
非剝脫性點(diǎn)陣激光亦可介導(dǎo)瘢痕的損傷修復(fù),促進(jìn)燒傷瘢痕紋理的改善。Haedersdal等[8]用1 540 nm點(diǎn)陣激光改善燒傷瘢痕,治療后外觀更光滑,但色素改善不明顯。除出現(xiàn)一過(guò)性紅斑、水腫和結(jié)痂、中度疼痛感外,不影響患者的日常活動(dòng),安全性較高。而Waibel等[9]證實(shí)1 550 nm非剝脫點(diǎn)陣鉺激光不僅能改善燒傷瘢痕的皮膚紋理,還可改善瘢痕異常色素外觀。
1.3 增生性瘢痕:增生性瘢痕的治療包括局封、干擾素、5氟尿嘧啶、冷凍、手術(shù)切除和放療等。氬激光、CO2激光和Nd:YAG激光曾用于治療增生性瘢痕,但療效多不穩(wěn)定,其復(fù)發(fā)率很高,故使用受限制;585 nm脈沖染料激光能改善增生性瘢痕的紅斑、紋理和柔韌度。
目前點(diǎn)陣激光治療增生性瘢痕尚有爭(zhēng)議,Niwa等[10]評(píng)估8例增生性瘢痕患者接受1 550 nm非剝脫點(diǎn)陣鉺激光治療,能量為35~50 mJ,8~10個(gè)療程,間隔1個(gè)月,結(jié)果平均改善級(jí)別為2.4,所有患者瘢痕的色素外觀均得到改善,但由于例數(shù)少,且無(wú)對(duì)照組,故尚未能肯定點(diǎn)陣鉺激光治療增生性瘢痕的療效。Verhaeghe等[11]通過(guò)隨機(jī)雙盲的方式評(píng)估1 540 nm非剝脫點(diǎn)陣激光治療增生性瘢痕,專(zhuān)業(yè)醫(yī)師對(duì)其療效不肯定,而患者認(rèn)為治療后局部外觀改善,其治療安全性高。
點(diǎn)陣激光治療光老化或嫩膚的機(jī)制考慮為熱刺激膠原再生有關(guān)[12]。Berlin 等[13]觀察點(diǎn)陣 CO2激光治療10例皮膚類(lèi)型為Ⅰ~Ⅲ型的光老化面部患者,療效肯定,組織學(xué)顯示,治療前光老化皮膚真皮乳頭層彈性組織變性,治療后真皮乳頭層大量成纖維細(xì)胞沉積,電鏡下見(jiàn)膠原纖維的平均直徑下降,主要由于Ⅲ型膠原較Ⅰ型膠原纖細(xì),提示有Ⅲ型膠原新生,從而在重塑過(guò)程中被Ⅰ型膠原替代。
點(diǎn)陣激光治療光老化的療效判定:色素斑、皺紋和皮膚紋理的改善程度。其中治療后色素斑的改善率明顯高于皺紋和皮膚紋理[14]。Tretti等[15]報(bào)道,點(diǎn)陣CO2激光治療光老化療效,治療后3個(gè)月療效最明顯,2年后隨訪其改善程度和半年后相似。
膨脹紋多由于體重快速增加、使用糖皮質(zhì)激素、妊娠、Cushing綜合征引起真皮快速膨脹牽拉引起,其治療較為棘手,1 540 nm非剝脫點(diǎn)陣鉺激光和點(diǎn)陣CO2激光可用于改善膨脹紋,改善率為51%~75%,無(wú)復(fù)發(fā),其作用機(jī)制可能為點(diǎn)陣激光照射后刺激真皮厚度增厚,促進(jìn)新生膠原、彈性纖維沉積有關(guān),不良反應(yīng)為一過(guò)性水腫、紅斑和少見(jiàn)PIH[16]。點(diǎn)陣CO2聯(lián)合脈沖染料激光治療膨脹紋比單一點(diǎn)陣CO2激光療效更佳,主要由于脈沖染料激光能改善膨脹紋的紅斑,且刺激增加更多膠原纖維。作者推薦先用點(diǎn)陣CO2激光治療膨脹紋,1~3周后再用脈沖染料激光改善其治療后出現(xiàn)紅斑,更有利于改善患者皮膚外觀,提高患者的滿意程度[17]。
黃褐斑是常見(jiàn)的色素異常性疾病,其特征是顏面蝶形淡褐色斑疹,明顯影響皮膚外觀,好發(fā)于亞洲人。點(diǎn)陣激光改善黃褐斑的機(jī)制是降低其色素形成和促進(jìn)膠原再生,對(duì)皮膚的彈性纖維無(wú)影響[18]。Goldberg等[19]觀察點(diǎn)陣激光治療黃褐斑后黑素細(xì)胞較前減少。電鏡顯示,治療后角質(zhì)形成細(xì)胞周?chē)纳丶?xì)胞和黑素分泌減少。Lee等[20]評(píng)估24例黃褐斑患者接受4個(gè)療程1 550 nm非剝脫點(diǎn)陣鉺激光治療后改善率為60%,4周后改善率降低到44%,患者黃褐斑的面積和嚴(yán)重指數(shù)(MASI)平均值由7.6降低到6.2,治療后黑素指標(biāo)明顯下降,但在隨訪中部分患者病情復(fù)發(fā),其中3例出現(xiàn)PIH。
不同波長(zhǎng)的點(diǎn)陣激光治療黃褐斑的療效不同。25例加拿大籍的黃褐斑患者接受平均為1.4個(gè)療程的Q開(kāi)關(guān)紅寶石點(diǎn)陣激光治療,結(jié)果顯示,MASI分?jǐn)?shù)由6.54降低到1.98(72.3%),治療3個(gè)月隨訪,7例患者(28%)出現(xiàn)PIH或病情反彈,明顯降低患者的滿意程度[21]。
Becker痣是較少見(jiàn)色素異常性疾病,可伴有多毛。到目前為止,尚未有一種有效的治療方法。Meesters等[22]嘗試用 CO2點(diǎn)陣激光治療 Becker痣,結(jié)果部分患者較滿意,醫(yī)師評(píng)估治療后外觀改善,但治療后通過(guò)共聚焦顯微鏡觀察黑素指數(shù)、黑素細(xì)胞的個(gè)數(shù)和真皮黑素并未減少。不良反應(yīng)表現(xiàn)為PIH、水腫、燒灼感、結(jié)痂、水皰,其中PIH明顯降低患者的滿意度。
治療文身的金標(biāo)準(zhǔn)[23]為Q開(kāi)關(guān)翠綠寶石、紅寶石和Nd:YAG激光,波長(zhǎng)分別為694、755、1 064 nm,多次治療能有效去除藍(lán)色、黑素和綠色的文身。Q開(kāi)關(guān)治療文身后,文身的墨水經(jīng)以下3個(gè)途徑排出:①經(jīng)表皮排出;②經(jīng)淋巴管排出;③經(jīng)真皮細(xì)胞吞噬再排出。Q開(kāi)關(guān)激光治療文身的缺點(diǎn)為遺留輕微瘢痕和對(duì)某些染料色素不敏感或?qū)€(gè)別色素可能導(dǎo)致顏色加深。Ibrahimi等[24]用2 940 nm點(diǎn)陣Er:YAG激光治療文身,經(jīng)過(guò)多次治療,文身的顏色大部分消退,但研究例數(shù)少,無(wú)對(duì)照。推薦采用點(diǎn)陣激光聯(lián)合Q開(kāi)關(guān)紅寶石激光治療文身療效更佳,考慮點(diǎn)陣激光能改善Q開(kāi)關(guān)紅寶石激光治療文身后遺留的色素減退[25]。
脂溢性角化病是皮膚常見(jiàn)的良性腫瘤,532 nm鉀鈦磷晶體激光、Er:YAG激光和Q開(kāi)關(guān)翠綠寶石/紅寶石激光等能有效治療脂溢性角化病。點(diǎn)陣激光改善色素考慮與微表皮壞死碎片將色素排出移出表皮有關(guān)。Polder等[26]證實(shí),1 927 nm 銩點(diǎn)陣激光能有效治療斑疹型脂溢性角化病,能量為10~20 mJ,30%~55%的治療覆蓋率,每個(gè)皮損重疊脈沖4~8次,結(jié)果脂溢性角化病的厚度變薄和數(shù)量減少。
雄激素性禿發(fā)的治療包括口服非那雄胺,局部使用米諾地爾和植發(fā)手術(shù)等。用于治療雄激素性禿發(fā)激光或光源有氦-氖激光、準(zhǔn)分子激光和UVA聯(lián)合補(bǔ)骨脂,其治療機(jī)制目前尚未清楚。有學(xué)者報(bào)道,20例雄激素性禿發(fā)患者接受1 550 nm非剝脫點(diǎn)陣鉺激光治療5個(gè)療程,治療間隔2周,自身對(duì)照,結(jié)果治療側(cè)明顯改善。通過(guò)動(dòng)物實(shí)驗(yàn)證實(shí),毛發(fā)刺激生長(zhǎng)的作用與激光的能量水平、密度和照射的間隔有關(guān),其作用機(jī)制考慮與點(diǎn)陣激光治療后毛囊生長(zhǎng)周期的分子信號(hào)、細(xì)胞因子和毛發(fā)生長(zhǎng)基因發(fā)生改變有關(guān),例如Wnt5a,β連環(huán)蛋白信號(hào)表達(dá)水平增加,從而刺激毛囊生長(zhǎng)[27]。
斑禿是由于毛囊周?chē)馨图?xì)胞浸潤(rùn)導(dǎo)致的毛囊凋亡。1例35歲的多發(fā)斑禿患者,既往2年采用5%米諾地爾、局部外用和皮損內(nèi)注射糖皮質(zhì)激素均無(wú)效,用點(diǎn)陣激光治療,每周1次,共24周,結(jié)果治療后第1周毛發(fā)開(kāi)始生長(zhǎng),6個(gè)月已完全長(zhǎng)好。其作用機(jī)制可能為介導(dǎo)T細(xì)胞凋亡和增強(qiáng)毛囊生長(zhǎng),另一可能機(jī)制是點(diǎn)陣激光照射頭皮后啟動(dòng)損傷修復(fù)過(guò)程,趨化淋巴細(xì)胞到達(dá)激光治療區(qū)域,故將毛囊周?chē)馨图?xì)胞浸潤(rùn)驅(qū)散[28]。
點(diǎn)陣激光能增加垂直通道,采用點(diǎn)陣激光照射皮膚后再外涂藥物,可增強(qiáng)局部藥物的吸收。其藥物導(dǎo)入通道與點(diǎn)陣激光的光斑密度和傳遞藥物的相對(duì)分子質(zhì)量有關(guān),一般認(rèn)為,點(diǎn)陣激光的光斑密度越大,經(jīng)皮滲透會(huì)越大,但光斑密度 >1%,則經(jīng)皮滲透反而下降。相對(duì)分子質(zhì)量大,則經(jīng)皮吸收遠(yuǎn)大于經(jīng)皮滲透,故藥物更容易保留在皮內(nèi)[29-30]。目前國(guó)內(nèi)有學(xué)者采用點(diǎn)陣CO2激光經(jīng)皮局部外用噻嗎洛爾溶液治療深部血管瘤取得良好療效[31]。
綜上所述,隨著人們對(duì)點(diǎn)陣激光的認(rèn)識(shí)增多,點(diǎn)陣激光適應(yīng)證較廣泛,但缺少大樣本、隨機(jī)雙盲的臨床研究,故仍待進(jìn)一步探討、拓展臨床適應(yīng)證。
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第五屆國(guó)際大皰病學(xué)術(shù)研討會(huì)通知
2015年10月24-25日在上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院召開(kāi)“第五屆國(guó)際大皰病學(xué)術(shù)研討會(huì)”。屆時(shí),美國(guó)賓夕法尼亞大學(xué)John Stanley、愛(ài)荷華大學(xué)Janet Fairley、北卡羅來(lái)納大學(xué)Zhi Liu、日本慶音大學(xué)Masayuki Amagai、德國(guó)呂貝克大學(xué)Detlef Zillinkens和法國(guó)魯昂大學(xué)醫(yī)院Pascal Joly等著名教授和國(guó)內(nèi)專(zhuān)家將做專(zhuān)題報(bào)道。此次會(huì)議還安排1天中國(guó)學(xué)者的發(fā)言,應(yīng)國(guó)外同行請(qǐng)求,PPT以雙語(yǔ)展示,用中文發(fā)言。這是一次純學(xué)術(shù)、顯示國(guó)際大皰病最高研究水平的會(huì)議,歡迎參加。會(huì)議不收注冊(cè)費(fèi),交通住宿費(fèi)自理。擬發(fā)言交流者請(qǐng)于2015年6月30日前將姓名、單位、聯(lián)系方式、發(fā)言題目和摘要發(fā)給聯(lián)系人;參加者請(qǐng)于2015年8月31日前將姓名、單位、聯(lián)系方式發(fā)給聯(lián)系人。聯(lián)系人:袁勇勇,Email:yyyluofan@163.com。
Clinical application of fractional lasers
Ma Shaoyin,Zhu Huilan.Guangzhou Institute of Dermatology,Guangzhou 510095,China
Because of definite efficacy,high safety and short downtime,fractional lasers have been successfully used for the treatment of acne scars and photoaging.Unlike traditional ablative and nonablative lasers,fractional lasers only act on some regions of the skin without involvement of surrounding nomal skin,allowing a rapid healing with short downtime.Fractional lasers deliver high energy to the dermis through micropores,which ensures efficacy and avoids common adverse reactions induced by traditional ablative lasers,such as permanent depigmentation and scarring.In this review,the authors summarize clinical application,action mechanism and efficacy of ablative and non-ablative fractional lasers in the treatment of scars,photoaging,striae atrophicae,pigmentary disorders,baldness,as well as in transdermal drug delivery.
Laser therapy;Cicatrix;Cell aging;Administration,cutaneous;Fractional lasers點(diǎn)陣激光是近10年的新技術(shù)之一,隨著人們對(duì)這門(mén)激光技術(shù)的掌握,點(diǎn)陣激光在臨床的應(yīng)用也越廣泛。
Zhu Huilan,Email:zhlhuilan@126.com
10.3760/cma.j.issn.1673-4173.2015.03.004
廣東省醫(yī)學(xué)科研基金(B2014347);廣州市衛(wèi)生科技項(xiàng)目(20141A011073)
510095廣州市皮膚病防治所
朱慧蘭,Email:zhlhuilan@126.com
2014-10-21)