曹麗媛,蔣鵬飛,顏春薇,劉培,彭俊,彭清華
〔摘要〕 蠕形螨是人類常見的體表寄生蟲之一,常因過度密集寄生體表而導致多種疾病產(chǎn)生。眼部蠕形螨感染癥狀多為瞼板腺功能障礙、瞼緣炎以及干眼等。干眼是一種常見的眼表炎癥性疾病,影響全球數(shù)億人。干眼病因較為復雜,近年研究報道表明其與蠕形螨感染關(guān)系密切。本文就蠕形螨與干眼的相關(guān)性研究進行理論探討,旨在推動蠕形螨相關(guān)性干眼防控向縱深發(fā)展,減少蠕形螨對人體眼部的傷害,為干眼的臨床診治提供新的參考依據(jù)和新思路。
〔關(guān)鍵詞〕 蠕形螨;干眼;理論探討;中醫(yī)藥;眼表炎癥;瞼板腺功能障礙;機制分析
〔中圖分類號〕R276.7? ? ? ?〔文獻標志碼〕A? ? ? ? 〔文章編號〕doi:10.3969/j.issn.1674-070X.2023.07.028
Correlation between Demodex and dry eye disease
CAO Liyuan1, JIANG Pengfei1, YAN Chunwei1, LIU Pei1, PENG Jun2, PENG Qinghua1*
1. Hunan University of Chinese Medicine, Changsha, Hunan 410208, China; 2. The First Hospital of Hunan
University of Chinese Medicine, Changsha, Hunan 410007, China
〔Abstract〕 Demodex is a common ectoparasite of human beings, and often causes a variety of diseases due to its high densities on the body surface. The symptoms of ocular Demodex infestation are mostly meibomian gland dysfunction, blepharitis, and dry eyes. Dry eye disease is a common ocular surface inflammatory disease that affects hundreds of millions of people worldwide. The causes of dry eye disease are complicated, and recent studies have shown that this disease is closely related to Demodex infestation. Through a theoretical discussion, this paper focuses on the correlation between Demodex and dry eye disease, aiming to promote the in-depth development of the prevention and control of Demodex-related dry eye disease, and reduce the damage of Demodex to human eyes, in the hope of providing a new reference and idea for clinical diagnosis and treatment of dry eye disease.
〔Keywords〕 Demodex; dry eye disease; theoretical discussion; Chinese medicine; ocular surface inflammation; meibomian gland dysfunction; mechanism analysis
蠕形螨(Demodex)是一類永久性體外寄生螨,主要寄生于人與哺乳動物的毛囊和皮脂腺內(nèi),目前已知種類有百余種,僅發(fā)現(xiàn)兩種能寄生于人體體表,即毛囊蠕形螨(Demodex folliculorum)和皮脂蠕形螨(Demodex brevis)[1]。蠕形螨屬于條件致病性寄生蟲,少量蠕形螨蟲體寄生體表通常不會導致疾病的發(fā)生,當蠕形螨種群數(shù)量增多或人體免疫力下降時,則可能會出現(xiàn)患病狀態(tài),如酒糟鼻、瞼緣炎、干眼以及普通皮炎等[2]。眼部蠕形螨病是由蠕形螨感染導致的一系列螨源性眼表疾病[3],眼部蠕形螨感染較普通面部蠕形螨感染造成的危害更為嚴重。近年來,蠕形螨感染引起的干眼的發(fā)病率日益升高,在此背景下,國內(nèi)外諸多學者投入眼部蠕形螨病的研究行列,展開了許多相關(guān)機制的研究[4-8]。本文主要對蠕形螨與干眼的相關(guān)性研究進行理論探討,以期為今后干眼的臨床診療提供更廣闊的思路。
1 蠕形螨與干眼的生理病理關(guān)系
蠕形螨是生活在哺乳動物皮膚上的小型外寄生蟲,具有高度復雜的生物學特性,其中毛囊蠕形螨蟲體較大,一般以群居方式寄居于人體眼部睫毛毛囊,易引發(fā)干眼癥狀;而皮脂腺蠕形螨蟲體較短,喜獨居,多寄居于人體眼睫毛根部皮脂腺和瞼板腺深處,主要引起眼后部瞼緣炎,因離體存活率極低,二者至今均未實現(xiàn)體外培養(yǎng)[9-10]。作用于人類眼部的蠕形螨主要是毛囊蠕形螨,毛囊蠕形螨主要在夜間活動,以體表皮膚異常分泌的油脂為食,雌性蠕形螨受精后便進入毛囊中發(fā)育,經(jīng)7~8 d成年后再至毛囊表層繼續(xù)活動,其在體表的生命活動周期為14~16 d[11-14]。2018年,亞洲干眼協(xié)會中國分會達成專家共識,一致認為眼部蠕形螨感染會導致干眼,其臨床癥狀表現(xiàn)為瞼緣發(fā)紅、眼癢、眼干、眼燒灼感、異物感、畏光及分泌物增多,嚴重者可伴有反復睫毛脫落、視物模糊或視力下降等[15-17]。
2 蠕形螨引起干眼的機制
干眼病變機制復雜,目前體內(nèi)和體外研究皆表明炎癥是干眼病變的核心[18]。多個臨床研究結(jié)果顯示,蠕形螨感染導致瞼板腺功能障礙可以影響淚膜的穩(wěn)定性和淚液的質(zhì)量,引發(fā)干眼[19]。臨床研究認為,每根睫毛毛囊檢測出5只蠕形螨即為被蠕形螨嚴重侵襲,但還未有研究表明引發(fā)干眼的蠕形螨感染的最小數(shù)目,蠕形螨相關(guān)性干眼的發(fā)病機制尚未十分明確[19]?,F(xiàn)階段認為蠕形螨引起干眼的機制可能主要有以下幾點。
2.1? 蠕形螨的機械性損害
蠕形螨體內(nèi)無排泄器官,卵過度繁殖堆積于睫毛根部引起卵泡擴張,而蟲體分泌物堆積于眼部皮膚,其中上皮細胞和角蛋白會沉積形成圓柱形鱗屑。研究發(fā)現(xiàn),圓柱形鱗屑中的螨脂肪酶和蛋白酶的酶促反應會導致眼表炎癥,引發(fā)眼部干澀、瘙癢、異物感、視物模糊等癥狀[20-21]。Cheng等[22]對119名具有干眼癥狀的患者進行了一項橫斷面研究,根據(jù)蠕形螨與干眼眼部表面參數(shù)間的關(guān)聯(lián),發(fā)現(xiàn)感染蠕形螨的個體伴有更嚴重的眼瞼異常和干眼癥狀。
2.2? 蠕形螨的載體作用
蠕形螨可直接作為病原微生物的載體,其蟲體出入毛囊和皮脂腺時會攜帶某些致病微生物進入瞼板腺導致繼發(fā)性感染,常見包括葡萄球菌和鏈球菌。這些病原微生物進入眼部會使脂質(zhì)淚膜發(fā)生改變,引起淚液過度蒸發(fā)和淚膜穩(wěn)定性降低,最終導致干眼[23]。PONDELIS教授將57名干眼患者與非干眼患者進行對比研究,研究結(jié)果顯示干眼患者眼表寄生的蠕形螨密度遠遠高出非干眼患者眼表寄生的蠕形螨密度[24]。
2.3? 宿主免疫力下降
正常人體體表皆可檢測出微量蠕形螨寄生,蠕形螨寄居宿主體表而生存,宿主免疫力下降時,蠕形螨會乘機大量繁殖,當蟲體數(shù)量達到臨界點,寄居在睫毛毛囊內(nèi)的蠕形螨會導致血管擴張、睫毛脆弱和周圍毛囊過度擴張,引發(fā)宿主的免疫反應及炎癥。目前,已有研究表明感冒、糖尿病、癌癥放化療、免疫缺陷患者中蠕形螨侵襲更嚴重[25]。JACOBI等[26]對73例輕度至重度干眼患者的睫毛蠕形螨情況進行研究,發(fā)現(xiàn)43.8%的患者眼瞼邊緣睫毛根部含有蠕形螨,且蠕形螨數(shù)量與年齡呈正相關(guān)性,隨著年齡增長,蠕形螨數(shù)量不斷增加,干眼癥狀也不斷加重。
總之,蠕形螨蟲體攝食及交配等活動產(chǎn)生機械性刺激和分泌物、代謝產(chǎn)物的化學刺激,以及蟲體出入毛囊、皮脂腺時攜帶某些致病微生物進入人體會引起淚液過度蒸發(fā)、淚膜穩(wěn)定性降低,最終導致周圍眼組織的炎癥,這是引起蠕形螨性干眼的主要原因[27]。越來越多的研究發(fā)現(xiàn),遷延不愈的干眼患者眼瞼中存在著大量蠕形螨寄居,在除螨治療后,干眼癥狀得到明顯改善,這從側(cè)面驗證了眼部蠕形螨具有干眼致病性的可能,眼部感染蠕形螨會直接導致或加重干眼的發(fā)生[28-32]。
3 蠕形螨相關(guān)性干眼的治療
目前,蠕形螨相關(guān)性干眼治療缺乏特效藥,治療措施主要有化學藥物、植物提取物及物理療法等。蠕形螨相關(guān)性干眼病程較長,停藥后易復發(fā),要注意早發(fā)現(xiàn)、早診斷、早治療,同步治療,避免相互擴散,以減少復發(fā)[33]。
3.1? 化學藥物
氯菊酯(permethrin)是一類廣譜殺蟲劑,對多種寄生蟲具有滅活作用。多項實驗研究發(fā)現(xiàn)氯菊酯在治療蠕形螨感染性眼病上具有良好的體外除螨效果[34-35]。HECHT等[36]用5%氯菊酯乳霜治療眼部蠕形螨患者6個月后發(fā)現(xiàn)患者眼部螨蟲數(shù)量明顯減少,眼干、眼癢及眼燒灼感等伴隨癥狀好轉(zhuǎn),且無不良反應。臨床上常協(xié)同使用玻璃酸鈉滴眼液以緩解眼睛干澀癥狀,效果良好[37]。
3.2? 植物提取物
蠕形螨相關(guān)性干眼的治療多以局部藥物殺螨為主,植物中提取的精油及其成分毒性低、易降解且不易產(chǎn)生耐藥,被認為是新型殺螨劑。茶樹油(tea tree
oil, TTO)已經(jīng)被證實可以有效殺除螨蟲,是具有殺螨作用的眼部局部藥物[38]。TTO在臨床上常被制成便攜的茶樹油眼貼及眼瞼清潔濕巾使用。JACOBI等團隊使用TTO提取物治療蠕形螨眼病4周后,發(fā)現(xiàn)蠕形螨蟲體數(shù)量減少將近一半,同時眼表疾病指數(shù)(ocular surface disease index, OSDI)降低至12~22分[39]。艾麗珍等研究了不同濃度茶樹精油對蠕形螨眼病的治療效果,結(jié)果表明15%的茶樹精油為治療蠕形螨眼病的最佳濃度,肯定了茶樹精油治療蠕形螨眼病的潛力[40]。蓖麻油是公認的抗炎劑,同時還具有抗氧化、促進傷口愈合和血管收縮的特性。研究表明,蓖麻油局部應用于眼表可以增加淚膜層厚度,改善蠕形螨引起的眼部炎癥和干眼癥狀[41-42]。
3.3? 物理療法
3.3.1? 瞼板腺按摩? 瞼板腺是位于眼皮瞼板內(nèi)的大皮脂腺,位置與瞼緣垂直,開口與瞼緣同向。每個腺體含10~15個分泌性腺泡,腺體通過腺泡分泌脂質(zhì)潤滑瞼緣、防止淚液外溢。蠕形螨與瞼板腺聯(lián)系密切,皮脂蠕形螨多寄居于瞼板腺導管,蟲體過度繁殖寄居及其代謝產(chǎn)物導致瞼板腺導管阻塞及瞼板腺分泌異常,引發(fā)瞼板腺功能障礙(meibomian gland dysfunction, MGD)。瞼板腺按摩是熱敷后借助外力按摩瞼板腺,排出瞼板腺導管內(nèi)溶解的脂質(zhì)和螨蟲代謝物,達到疏通瞼板腺導管的作用。LIN等對38例蠕形螨導致的MGD患者展開研究,發(fā)現(xiàn)瞼板腺按摩聯(lián)合治療比單純藥物治療更能改善患者干眼情況[43]。
3.3.2? 強脈沖光(intense pulsed light, IPL)療法? LPL是現(xiàn)代一種抑制炎癥介質(zhì)的光治療技術(shù),因?qū)∧w淺表損傷疾病有較好作用,被廣泛應用于臨床。CHENG等[44]對25例蠕形螨眼病患者進行了回顧性研究,發(fā)現(xiàn)經(jīng)過IPL治療后,患者睫毛根部螨蟲數(shù)量逐漸減少,其伴隨的MGD癥狀和干眼癥狀得到明顯改善。有研究對47例門診干眼患者使用IPL進行治療后癥狀改善,睫毛處的鱗屑與分泌物有所減少,且無明顯不良反應,證明了IPL對于蠕形螨相關(guān)性干眼具有安全有效的治療作用[45]。
3.3.3? 中醫(yī)治療? 蠕形螨相關(guān)性干眼在中醫(yī)古籍中無明確記載,后世醫(yī)家常將蠕形螨相關(guān)性干眼歸屬于“白澀癥”“風沿爛眼”等范疇。胞瞼屬于中醫(yī)五輪學說的肉輪,在臟屬脾,蠕形螨相關(guān)性干眼當先從脾胃論治。現(xiàn)代中醫(yī)各家對于該病的中醫(yī)辨證分型不盡相同,目前尚無統(tǒng)一的蠕形螨相關(guān)性干眼的辨證標準。中醫(yī)作為傳統(tǒng)醫(yī)藥,除了傳統(tǒng)的湯劑內(nèi)服治療外,還有獨具特色的中醫(yī)外治法。外治法在治療眼部蠕形螨感染方面也有其獨特優(yōu)勢。許多中藥既具有殺螨作用又兼有抗菌作用,且除螨效果良好[46]。艾葉是典型的天然抗炎殺菌中藥,艾灸是傳統(tǒng)中醫(yī)外治技術(shù),艾葉點燃后的揮發(fā)性氣味可以引起蠕形螨劇烈翻滾扭動,加劇蟲體死亡,達到驅(qū)螨效果[47-48]。隨著中醫(yī)藥學的不斷發(fā)展,現(xiàn)代技術(shù)與中藥聯(lián)系日益緊密,中藥超聲霧化治療技術(shù)應運而生。現(xiàn)代研究表明中藥超聲霧化治療不僅用藥量小、不良反應少,還可以有效促進局部炎癥的消退、加速組織修復。臨床上使用超聲波將相應中藥湯液霧化成極細霧狀顆粒,使藥物在瞼緣均勻敷布,疏通瞼板腺口以達到緩解眼部干澀等不適癥狀的效果。中藥超聲霧化治療蠕形螨相關(guān)性干眼方便簡練,安全且無毒副作用[49-50]。
3.4? 日常預防
未病先防,蠕形螨主要通過直接或間接接觸傳播,預防應當置于首位[51]。避免直接接觸蠕形螨感染者,注意個人衛(wèi)生及日常生活清潔,定期換洗毛巾,晾曬被褥等貼身物品;注意居住環(huán)境衛(wèi)生,保持室內(nèi)適宜的溫度、濕度;清淡飲食,少食肥甘厚膩;保持顏面部潔凈,勿用手揉搓眼部;日常可局部熱敷眼瞼以免眼疲勞、干澀。
4 結(jié)語
人體蠕形螨是一類永久性寄生蟲,其在眼部造成的感染情況日益受到眼科領域重視。目前,蠕形螨感染造成的MGD的研究報道較多,干眼與瞼板腺功能障礙密切相關(guān),但在國內(nèi)外研究報道中蠕形螨感染與干眼的相關(guān)性仍涉及較少。本文僅對蠕形螨與干眼相關(guān)性研究作出綜述,蠕形螨相關(guān)性干眼的致病條件及致病機制尚未十分明確,需進一步研究以提高對蠕形螨相關(guān)性干眼的臨床認識,以期為今后蠕形螨相關(guān)性干眼的預防和治療提供可靠依據(jù)。
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