IJavascript ivaliwe okwangoku kwibrawuza yakho.Xa i-javascript ivaliwe, eminye imisebenzi yale webhusayithi ayiyi kusebenza.
Bhalisa iinkcukacha zakho ezithile kunye neziyobisi ezithile ezinomdla, kwaye siya kuhambelana nolwazi osinika lona kunye namanqaku kwidathabheyisi yethu ebanzi kwaye sikuthumelele ikopi yePDF nge-imeyile ngexesha elifanelekileyo.
Agnieszka Owczarczyk-Saczonek, Natalia Zdanowska, Ewa Wygonowska, Waldemar Placek iSebe leDermatology, izifo eziSasalela ngeSondo kunye neClinical Immunology, iWarmia kunye neYunivesithi yaseMazury e-Olsztyn, incwadana yeendaba yasePoland: i-Agnieszka iDermatology yeSebe, i-Imczarczy yeSifo se-Agnieszka, i-Immunology yeCandelo le-Immunology ye-Owczarczy IYunivesithi yaseWarmia kunye neMazury, eOlsztyn, ePoland.Wojska Polskiego 30, Olsztyn, 10-229, PolishTel +48 89 6786670 Fax +48 89 6786641 Email [i-imeyile ekhuselweyo] Abstract: Hyaluronic acid (HA) yi-glycosaminoglycan, icandelo lendalo le-extracellular matrix.Ulwakhiwo olufanayo lwemolekyuli kuzo zonke izinto eziphilayo yeyona nto iluncedo kuba inethuba elincinci lokuguqulwa libe yi-immunogenicity.Ke ngoko, ngenxa ye-biocompatibility yayo kunye nokuzinza kwindawo yokufakelwa, yeyona ndlela isondeleyo ifanelekileyo yokusetyenziswa njengento yokuzalisa.Eli nqaku libandakanya ingxoxo yendlela esisiseko ye-HA's engalunganga yokusabela komzimba, kunye nendlela yokuphendula emva kogonyo oluchasene ne-SARS-CoV-2.Ngokutsho kweencwadi, sizame ukucwangcisa impendulo engalunganga ye-immune kunye nokubonakaliswa kwenkqubo kwi-HA.Ukwenzeka kweempendulo ezingalindelekanga kwi-asidi ye-hyaluronic kubonisa ukuba abanakuthatyathwa njengento engathathi hlangothi okanye engekho-allergenic.Utshintsho kwisakhiwo seekhemikhali ze-HA, izongezo, kunye nokuthambekela komntu ngamnye kwizigulane zinokuba yimbangela yokuphendula okungalindelekanga, okukhokelela kwimiphumo emibi yempilo.Ukulungiselela imvelaphi engaziwayo, ukuhlanjululwa kakubi, okanye i-DNA yebhaktheriya iyingozi kakhulu.Ngoko ke, ukulandelwa kwexesha elide lezigulane kunye nokukhethwa kwe-FDA okanye i-EMA amalungiselelo avunyiweyo abaluleke kakhulu.Izigulana zihlala zingazazi iziphumo zotyando oluphantsi olwenziwa ngabantu ngaphandle kolwazi olululo kusetyenziswa iimveliso ezingabhaliswanga, ngoko ke uluntu kufuneka lufundiswe kwaye kuqaliswe imithetho nemigaqo.Amagama angundoqo: i-Hyaluroniki acid, izigcwalisi, ukudumba okulibazisekayo, i-autoimmune/auto-inflammatory adjuvant-induced syndrome, i-SARS-CoV-2
I-asidi ye-Hyaluronic (HA) yi-glycosaminoglycan, inxalenye yendalo ye-matrix engaphandle.Iveliswa yidermal fibroblasts, iiseli ze-synovial, iiseli ze-endothelial, iiseli ze-muscle ezigudileyo, iiseli ze-adventitia kunye nee-oocytes kwaye zikhutshwe kwindawo ejikelezileyo ye-extracellular.I-1,2 Isakhiwo esifanayo seemolekyuli kuzo zonke izinto eziphilayo iyona nzuzo enkulu, ehambelana nomngcipheko omncinci we-immunogenicity.I-biocompatibility kunye nozinzo lwesiza sofakelo lwenza ukuba lube lolona khetho lufanelekileyo kulo lonke uthotho lokugcwalisa.Ngenxa yokwandiswa komatshini kwezicubu emva kokutofa kunye nokusebenza okulandelayo kwe-fibroblasts yesikhumba, kunenzuzo enkulu yokukwazi ukuvuselela ukuveliswa kwe-collagen entsha.I-2-4 i-Hyaluronic acid i-hydrophilic ephezulu, ineempawu ezikhethekileyo zokubopha iimolekyuli zamanzi (ngaphezu kwamaxesha angama-1000 ubunzima bayo), kwaye yenza i-conformation eyandisiweyo kunye nomthamo omkhulu xa kuthelekiswa nobunzima.Isenokwenza i-condensation nakwiqondo eliphantsi kakhulu.iglu.Ibangela ukuba izicubu zikhuphe ngokukhawuleza kwaye zinyuse umthamo wesikhumba.I-3,5,6 Ukongezelela, ukunyuswa kwesikhumba kunye ne-antioxidant ye-hyaluronic acid inokukhuthaza ukuvuselelwa kweeseli zesikhumba kunye nokukhuthaza ukuveliswa kwe-collagen.5
Ukutyhubela iminyaka, kuye kwaphawulwa ukuba ukuthandwa kweenkqubo zokuthambisa usebenzisa izinto ezifana ne-HA ziye zaqhubeka nokukhula.Ngokutsho kwedatha evela kwi-International Society of Aesthetic Plastic Surgery (ISAPS), ngaphezu kwe-4.3 yezigidi zeenkqubo zokuthambisa zenziwe ngokusebenzisa i-HA ngo-2019, ukwanda kwe-15.7% xa kuthelekiswa no-2018. I-American Society of Dermatology (ASDS) ibika ukuba i-dermatologists yenza i-2.7 million dermal filler injections ngo-2019. 8 Ukuphunyezwa kweenkqubo ezinjalo kuba yindlela enenzuzo kakhulu yomsebenzi ohlawulelwayo.Ngoko ke, ngenxa yokungabikho kwemithetho kunye nemimiselo kumazwe / imimandla emininzi, abantu abaninzi ngakumbi banikezela ngeenkonzo ezinjalo, ngokuqhelekileyo ngaphandle koqeqesho olufanelekileyo okanye iziqinisekiso.Ukongeza, kukho iifomyula ezikhuphisanayo kwimarike.Zisenokuba zixabiso eliphantsi, zomgangatho ophantsi, kwaye azivunywanga yi-FDA okanye i-EMA, nto leyo engumngcipheko wophuhliso lweentlobo ezintsha zokusabela okubi.Ngokophononongo olwenziwe eBelgium, uninzi lweesampulu ezili-14 ekurhaneleka ukuba ziye zavavanywa ziqulethe iimveliso ezingaphantsi kakhulu kunezichazwe kwipakethe.9 Amazwe amaninzi aneenkqubo zokuthambisa ezingekho mthethweni.Ukongeza, ezi nkqubo azibhaliswanga kwaye akukho rhafu ihlawulwayo.
Ngoko ke, kukho iingxelo ezininzi zeziganeko ezimbi kwiincwadi.Ezi ziganeko zingalunganga zihlala zikhokelela kuxilongo olumandla kunye neengxaki zonyango kunye neziphumo ezingalindelekanga kwizigulana.I-7,8 Hypersensitivity kwi-hyaluronic acid ibaluleke kakhulu.I-pathogenesis yezinye iimpendulo azikacaciswanga ngokupheleleyo, ngoko ke isigama kuncwadi asifani, kwaye iimvumelwano ezininzi malunga nokulawulwa kweengxaki azikafaki ukusabela okunjalo.10,11
Eli nqaku libandakanya idatha evela kuphononongo loncwadi.Chonga amanqaku ovavanyo ngokukhangela kwi-PubMed usebenzisa la mabinzana alandelayo: i-hyaluronic acid, iifayili, kunye nemiphumo emibi.Ukhangelo luyaqhubeka de kube ngoMatshi 30, 2021. Kufunyenwe amanqaku ayi-105 kwaye kuhlalutywe angama-42 kuwo.
I-asidi ye-Hyaluroniki ayilona ilungu okanye iintlobo ezithile, ngoko kunokucingelwa ukuba ayibangeli ukusabela komzimba.12 Nangona kunjalo, kubalulekile ukukhumbula ukuba imveliso ejojowe ibandakanya izongezo, kwaye i-asidi ye-hyaluronic ifumaneka nge-bacterial biosynthesis.
Kwakhona kuye kwaboniswa ukuba ukuthambekela komntu ngamnye kunokukhokelela kumngcipheko wokulibaziseka, ukusabela okungalunganga kwe-immune-mediated okuhambelana nokuzaliswa kwedermal kwizigulane ezithwele i-HLA-B * 08 kunye ne-DR1 * 03 haplotypes.Oku kudityaniswa kwe-HLA subtypes kudibaniswa nokunyuka okuphindwe kane kumathuba okuphendula okungalunganga (OR 3.79).13
I-asidi ye-Hyaluroniki ikhona ngendlela yee-multiparticulates, ukuyila kwayo kulula, kodwa i-biomolecule esebenzayo.Ubungakanani be-HA buchaphazela umphumo ochaseneyo: unokuba neepropathi ze-pro-inflammatory okanye ezichasayo, ukukhuthaza okanye ukuvimbela ukufuduka kweeseli, kwaye kusebenze okanye ukuyeka ukuhlukana kweeseli kunye nokwahlula.14-16 Ngokudabukisayo, akukho mvumelwano malunga nokwahlulwa kwe-HA.Igama lobungakanani bemolekyuli.14,16,17
Xa usebenzisa iimveliso ze-HMW-HA, kuyafaneleka ukukhumbula ukuba i-hyaluronidase yendalo ibangela ukuthotywa kwayo kwaye ikhuthaza ukubunjwa kwe-LMW-HA.I-HYAL2 (i-anchored on the cell membrane) iqhekeza ubunzima obuphezulu be-molecular HA (> 1 MDa) kwiinqununu ze-20 kDa.Ukongezelela, ukuba i-HA hypersensitivity iqala, ukuvuvukala kuya kukhuthaza ukuthotywa kwayo ngakumbi (Umfanekiso 1).
Kwimeko yeemveliso ze-HA, kunokubakho ukungafani kwinkcazo yobungakanani bemolekyuli.Ngokomzekelo, kwiqela leemveliso zeJuvederm (Allergan), iimolekyuli> 500 kDa zibhekwa njenge-LMW-HA, kunye> 5000 kDa - HMW-HA.Kuya kuchaphazela ukuphuculwa kokhuseleko lwemveliso.18
Kwezinye iimeko, ubunzima obuphantsi be-molecular (LMW) HA bunokubangela i-hypersensitivity 14 (Umfanekiso 2).Ithathwa njengemolekyuli ye-pro-inflammatory.Ifumaneka kakhulu kwiindawo ezisebenzayo ze-tissue catabolism, umzekelo, emva kokulimala, kubangela ukuvuvukala ngokuchaphazela i-Toll-like receptors (TLR2, TLR4).I-14-16,19 Ngale ndlela, i-LMW-HA ikhuthaza ukusebenza kunye nokuvuthwa kweeseli ze-dendritic (DC), kwaye ivuselela iintlobo ezahlukeneyo zeeseli ukuvelisa i-cytokines e-pro-inflammatory, njenge-IL-1β, IL-6, IL-12 , TNF-α kunye ne-TGF-β, ilawula ukubonakaliswa kwee-chemokines kunye nokufuduka kweeseli.I-14,17,20 i-LMW-HA inokusebenza njengemodeli yemolekyuli enxulumene nobungozi (i-DAMP) ukuqalisa iindlela zokuzivikela ezizalwa, ezifana neeprotheni zebhaktheriya okanye iiprotheni zokutshatyalaliswa kobushushu.I-14,21 CD44 isebenza njengendlela yokuqaphela ipateni ye-receptor ye-LMW-HA.Ikhona kumphezulu wazo zonke iiseli zomntu kwaye inokunxibelelana nezinye iiligand ezifana ne-osteopontin, collagen, kunye ne-matrix metalloproteinases (MMP).14,16,17.
Emva kokuba ukuvuvukala kuphelile kwaye iintsalela zezicubu ezonakalisiweyo zipheliswe yi-macrophages, i-molecule ye-LMW-HA isuswe yi-CD44 exhomekeke kwi-endocytosis.Ngokwahlukileyo, ukuvuvukala okungapheliyo kuhambelana nokunyuka kwexabiso le-LMW-HA, ngoko ke banokuthathwa njengezinto eziphilayo zendalo zesimo sokunyaniseka kwezicubu.I-14,20,22,23 Indima ye-CD44 receptor ye-HA ibonakaliswe kwizifundo malunga nokulawulwa kokuvuvukala phantsi kweemeko ze-vivo.Kwiimodeli zemouse ye-atopic dermatitis, unyango lwe-anti-CD44 luvimbela ukuphuhliswa kweemeko ezifana ne-collagen-induced arthritis okanye umonakalo wesikhumba.amashumi amabini anesine
Ubunzima obuphezulu be-molecular (HMW) HA buxhaphake kwizicubu eziqinileyo.Ivimbela ukuveliswa kwe-pro-inflammatory mediators (IL-1β, IL-8, IL-17, TNF-α, metalloproteinases), iyanciphisa ukubonakaliswa kwe-TLR kwaye ilawula i-angiogenesis.I-14,19 HMW-HA iphinda ichaphazele umsebenzi we-macrophages ojongene nokulawula ngokuvuselela umsebenzi wabo wokuchasana nokuvuvukala ukuphucula ukuvuvukala kwendawo.15,24,25
Isixa esipheleleyo se-hyaluronic acid kumntu olinganisa i-70 kg malunga ne-15 grams, kwaye izinga layo lokubuyisela liyi-5 grams ngosuku.Ngokumalunga ne-50% ye-hyaluronic acid emzimbeni womntu igxininiswe esikhumbeni.Isiqingatha-ubomi bayo ziiyure ezingama-24-48.I-22,26 Ngoko ke, i-half-life ye-HA engaguqukiyo yendalo ngaphambi kokuba ihlanjululwe ngokukhawuleza nge-hyaluronidase, i-enzyme ye-tissue yendalo kunye neentlobo ze-oksijini ezisebenzayo kuphela malunga neeyure ze-12.I-27,28 I-chain ye-HA yaphuhliswa ukwandisa ukuzinza kwayo kwaye ivelise iamolekyu ezinkulu kunye nezinzile, kunye nexesha elide lokuhlala kwi-tissue (malunga neenyanga eziliqela), kunye ne-biocompatibility efanayo kunye neempawu zokuzaliswa kwe-viscoelastic.I-28 i-Crosslinking ibandakanya umlinganiselo ophezulu we-HA edibeneyo kunye ne-molecule ephantsi ye-molecular weight weight and the low ratio of high molecular weight HA.Olu hlengahlengiso lutshintsha ukuhambelana kwendalo kwe-molecule ye-HA kwaye inokuchaphazela ukungazinzi kwayo.18
I-Cross-linking ikakhulu ibandakanya ukudibanisa i-polymers ukwenza i-covalent bonds, ngokukodwa kubandakanywa (-COOH) kunye / okanye i-hydroxyl (-OH) yamathambo.Iikhompawundi ezithile zinokukhuthaza ukunqumla, njenge-1,4-butanediol diglycidyl ether (BDDE) (Juvederm, Restylane, Princess), i-divinyl sulfone (Captique, Hylaform, Prevelle) okanye i-diepoxy octane (Puragen).29 Nangona kunjalo, amaqela e-epoxy e-BDDE angathathi hlangothi emva kokuphendula nge-HA, ngoko ke kuphela ukulandelela amanani e-BDDE engaphendulwanga (<2 iinxalenye ngesigidi) inokufumaneka kwimveliso.I-26 i-Cross-linked ha hydrogel yinto eguquguqukayo kakhulu engakhokelela ekubunjweni kwezakhiwo ze-3D ezineempawu ezizodwa (rheology, degradation, applicability).Ezi mpawu zikhuthaza ukuhanjiswa lula kwemveliso kwaye ngexesha elifanayo likhuthaza ukuveliswa kwamacandelo eemolekyuli ze-matrix engaphandle.30,31<>
Ukuze kwandiswe i-hydrophilicity yemveliso, abanye abavelisi bongeza ezinye iikhompawundi, ezifana ne-dextran okanye i-mannitol.Nganye kwezi zongezo zinokuba yi-antigen evuselela impendulo yomzimba.
Okwangoku, amalungiselelo e-HA aveliswa kwiintlobo ezithile zeStreptococcus ngokusebenzisa ukuvutshelwa kwebhaktheriya.(Streptococcus equi okanye Streptococcus zooepidemicus).Xa kuthelekiswa namalungiselelo asele esetyenziswe kwizilwanyana, kunciphisa umngcipheko we-immunogenicity, kodwa ayikwazi ukuphelisa ukungcoliswa kweemolekyuli zeprotheni, i-nucleic acids ye-bacterial kunye ne-stabilizers.Zinokuba zii-antigens kwaye zivuselele impendulo yokhuselo lomkhosi, njenge-hypersensitivity kwiimveliso ze-HA.Ke ngoko, itekhnoloji yokuvelisa i-filler (efana ne-Restylane) igxile ekunciphiseni ukungcoliseka kwemveliso.32
Ngokutsho kwenye i-hypothesis, impendulo ye-immune kwi-HA ibangelwa ukuvuvukala okubangelwa ngamacandelo ebhaktheriya e-biofilm, ezithunyelwa kwiiscuphe xa imveliso ijojowe.I-33,34 i-Biofilm yenziwe ngebhaktheriya, izondlo zabo kunye ne-metabolites.Ikakhulu ibandakanya iibhaktheriya eziphambili ezingezizo ze-pathogenic ezithatha ulusu olusempilweni okanye iinwebu (umzekelo, i-Dermatobacterium acnes, i-Streptococcus oralis, i-Staphylococcus epidermidis).Olu xinzelelo luye lwaqinisekiswa luvavanyo lwe-polymerase chain reaction.33-35
Ngenxa yeempawu zabo ezizodwa ezikhula ngokucothayo kunye nokwahluka kwazo okubizwa ngokuba ziikholoni ezincinci, kuhlala kunzima ukuchonga iintsholongwane kwinkcubeko.Ukongezelela, i-metabolism yabo kwi-biofilm inokunciphisa, enceda ukuphepha imiphumo ye-antibiotics.I-35,36 Ukongezelela, ukukwazi ukwenza i-matrix ye-extracellular ye-polysaccharides ye-extracellular (kubandakanywa ne-HA) yinto yokukhusela i-phagocytosis.Ezi bhaktheriya zinokuhlala zilele iminyaka emininzi, emva koko zenziwe zisebenze zizinto zangaphandle kwaye zibangele ukusabela.I-35-37 i-Macrophages kunye neeseli ezinkulu zihlala zifumaneka kwindawo ekufutshane nezi microorganisms.Zinokuthi zisebenze ngokukhawuleza kwaye zenze impendulo yokuvuvukala.38 Izinto ezithile, ezifana nosulelo lwebhaktiriya oluneentlobo zebhaktiriya ezifanayo ekubunjweni kwebhayofilim, zingenza i-microorganisms eleleyo isebenze ngeendlela zokulinganisa.Ukusebenza kusenokuba ngenxa yomonakalo owenziwe yenye inkqubo yokuzalisa idermal.38
Kunzima ukwahlula phakathi kokuvuvukala kunye nokulibaziseka kwe-hypersensitivity okubangelwa yi-bacterial biofilms.Ukuba i-red sclerotic lesion ibonakala nangaliphi na ixesha emva kokuhlinzwa, kungakhathaliseki ukuba ixesha elide, i-biofilm kufuneka ikrokre ngokukhawuleza.I-38 Inokuthi i-asymmetrical kunye ne-symmetrical, kwaye ngamanye amaxesha inokuchaphazela zonke iindawo apho i-HA ilawulwa khona ngexesha lotyando.Nokuba isiphumo senkcubeko sibi, isithinteli-ntsholongwane esibanzi esinokungena kakuhle eluswini kufuneka sisetyenziswe.Ukuba kukho amaqhuqhuva aneefayibha anoxhathiso olwandayo, kusenokwenzeka ukuba yigranuloma yomzimba wangaphandle.
I-HA inokuphinda ivuselele ukuvuvukala ngokusebenzisa i-superantigens.Le mpendulo ayifuni izigaba zokuqala zokuvuvukala.I-12,39 i-Superantigens ibangela i-40% yeeseli ze-T zokuqala kwaye mhlawumbi i-NKT clonal activation.Ukusetyenziswa kwezi lymphocytes kukhokelela kwisivunguvungu se-cytokine, esibonakaliswe ngokukhululwa kwee-cytokines ze-pro-inflammatory, ezifana ne-IL-1β, IL-2, IL-6 kunye ne-TNF-α40.
I-pneumonia enzima, ehlala ihamba kunye nokungaphumeleli okukhulu kokuphefumla, ngumzekelo wempendulo ye-pathological superantigen ye-bacterial (staphylococcal enterotoxin B), eyandisa i-LMW-HA eveliswa yi-fibroblasts kwizicubu zemiphunga.I-HA ivuselela ukuveliswa kwe-IL-8 kunye ne-IP-10 chemokines, edlala indima ebalulekileyo ekufuneni iiseli ezivuthayo kwimiphunga.I-40,41 Iindlela ezifanayo ziye zabonwa ngexesha le-asthma, isifo esingapheliyo se-pulmonary obstructive and pneumonia.Ukonyuka kwemveliso ye-COVID-19.41 LMW-HA kukhokelela ekuvuseleleni ngokugqithiseleyo kwe-CD44 kunye nokukhululwa kwee-cytokines ezi-pro-inflammatory kunye nee-chemokines.40 Le ndlela yokusebenza inokubonwa nasekudumbeni okubangelwa ngamacandelo ebhayofilm.
Xa iteknoloji yokuvelisa i-filler yayingachanekanga kangako ngo-1999, umngcipheko wokulibaziseka kokusabela emva kwesitofu se-HA kwamiselwa ukuba yi-0.7%.Emva kokuqaliswa kweemveliso ezicocekileyo, iziganeko zeziganeko ezimbi ezinjalo zehla kwi-0.02%.I-3,42,43 Nangona kunjalo, ukuqaliswa kwee-HA fillers ezidibanisa amakhonkco aphezulu kunye ne-HA ephantsi kubangele iipesenti eziphezulu ze-AE.44
Idatha yokuqala malunga nokuphendula okunjalo yavela kwingxelo yokusetyenziswa kwe-NASHA.Le yi-erythema kunye ne-edema reaction, kunye nokungeniswa kunye ne-edema kwindawo ejikelezileyo ehlala kwiintsuku ze-15.Le mpendulo yabonwa kwi-1 yezigulane ze-1400.I-3 Abanye ababhali baye babika ii-nodules ezivuthayo ezihlala ixesha elide, ezenzeka kwi-0.8% yezigulane.45 Bagxininisa i-etiology enxulumene nokungcoliswa kweeprotheyini okubangelwa ukuvutshelwa kwebhaktheriya.Ngokutsho kweencwadi, ukuphindaphinda kweempendulo ezimbi ngu-0.15-0.42%.3,6,43
Kwimeko yokusebenzisa umlinganiselo wexesha, kukho iinzame ezininzi zokuhlela iziphumo ezibi ze-HA.46
Bitterman-Deutsch et al.yahlelwa izizathu zokusabela okubi kunye neengxaki emva kotyando kunye namalungiselelo asekelwe kwi-hyaluronic acid.Ziquka
Iqela leengcali lizama ukuchaza impendulo kwi-hyaluronic acid esekelwe kwixesha lokubonakala emva kokuhlinzwa: "ekuqaleni" (<14 iintsuku), "kade" (> Iintsuku eziyi-14 ukuya kwi-1 ngonyaka) okanye "ukulibaziseka" (> 1 unyaka).I-47-49 Abanye ababhali bahlula impendulo ekuqaleni (ukuya kwiveki enye), phakathi (ixesha: iveki enye ukuya kwinyanga enye), kwaye emva kwexesha (ngaphezu kwenyanga enye).50 Okwangoku, iimpendulo ezifike emva kwexesha kunye nokulibaziseka zithathwa njengequmrhu elinye, elibizwa ngokuba yi-deacted inflammatory response (DIR), kuba izizathu zabo zihlala zingachazwanga ngokucacileyo kwaye unyango aluhambelani nonobangela.42 Ukuhlelwa kwezi mpendulo kunokuphakanyiswa ngokusekelwe kuncwadi (Umfanekiso 3).
I-edema yethutyana kwindawo yokutofa ngokukhawuleza emva kotyando inokuba ngenxa yendlela yokukhupha i-histamine kwizigulana ezithanda udidi loku-1 lweziphumo zokwaliwa, ngakumbi ezo zinembali yezifo zolusu.51 Yimizuzu nje embalwa emva kolawulo apho iiseli zemast zonakaliswe ngoomatshini kwaye zikhulule abalamli be-pro-inflammatory ukuze babangele i-tissue edema kunye nokwakheka kobunzima bomoya.Ukuba impendulo ebandakanya iiseli zemast yenzeke, ikhosi yonyango lwe-antihistamine idla ngokwaneleyo.51
Umonakalo omkhulu wesikhumba obangelwa utyando lokuthambisa, i-edema enkulu, enokuthi iqhubele phambili kwi-10-50%.52 Ngokutsho kwedayari yesigulane esineemfama eziphindwe kabini ezingaboniyo, ukuphindaphinda kwe-edema emva kwenaliti ye-Restylane kuqikelelwa ukuba yi-87% yophononongo lwe-52,53.
Iindawo ezisebusweni ezibonakala zixhomekeke kakhulu kwi-edema yimilebe, i-periorbital kunye neendawo zehlathi.52 Ukuze kuncitshiswe umngcipheko, kucetyiswa ukuba ugweme ukusetyenziswa kwezixa ezininzi zokuzalisa, i-anesthesia yokungena, i-massage esebenzayo kunye namalungiselelo e-hygroscopic kakhulu.Izongezo (i-mannitol, i-dextran).52
I-Edema kwindawo yokutofa ehlala imizuzu emininzi ukuya kwiintsuku ze-2-3 inokubangelwa yi-hygroscopicity ye-HA.Le mpendulo idla ngokubonwa kwindawo yeperilip kunye ne-periorbital.I-49,54 akufanele iphoswe nge-edema ebangelwa yindlela enqabileyo kakhulu yokusabela ngokukhawuleza (i-angioedema).49
Emva kwesitofu se-Restylane (NASHA) emlonyeni ophezulu, imeko ye-hypersensitivity kwi-angioedema yachazwa.Nangona kunjalo, isigulana siphinde sathatha i-2% ye-lidocaine, enokuthi ibangele uhlobo lwe-I hypersensitivity reaction.Ukulawulwa kwenkqubo ye-corticosteroids kubangele ukuba i-edema iyancipha kwiintsuku ze-4.32
Ukusabela okukhawulezileyo kusenokuba ngenxa yobuntununtunu bokungcoliseka kwentsalela yeprotein ye-HA synthesizing bacteria.Ukusebenzisana phakathi kwe-HA ejojowe kunye neeseli ze-mast ezisele kwi-tissue enye indlela yokucacisa into yokuphendula ngokukhawuleza.I-CD44 receptor kumphezulu weeseli zemast yi-receptor ye-HA, kwaye oku kusebenzisana kunokubaluleka ekufudukeni kwabo.32,55
Unyango lubandakanya ukulawulwa kwangoko kwee-antihistamines, i-systemic GCS, okanye i-epinephrine.46
Ingxelo yokuqala, epapashwe nguTurkmani et al., Yachaza abafazi abaneminyaka eyi-22-65 abaye bafumana utyando lwe-HA oluveliswe ziinkampani ezahlukeneyo.39 Izilonda zesikhumba zibonakaliswa yi-erythema kunye ne-edema ebuhlungu kwindawo yokutofa kwe-filler ebusweni.Kuzo zonke iimeko, impendulo iqala emva kweentsuku ezi-3-5 emva kokugula okufana nomkhuhlane (umkhuhlane, intloko ebuhlungu, umqala obuhlungu, ukukhohlela, kunye nokudinwa).Ukongezelela, zonke izigulane zifumene ulawulo lwe-HA (i-2 ukuya kwii-6 amaxesha) kwiminyaka eyi-4 ngaphambi kokuba iimpawu zivele kwiindawo ezahlukeneyo zobuso.39
Inkcazo yeklinikhi yendlela yokusabela echazwe (i-erythema kunye ne-edema okanye i-urticaria-efana ne-rash ene-systemic manifestations) iyafana nohlobo lwe-III yokusabela-impendulo yokugula kwe-pseudoserum.Ngelishwa, akukho ngxelo kwiincwadi eziqinisekisa le ngcamango.Ingxelo yecala ichaza isigulane esine-rash-like lesion ngexesha le-Sweet syndrome, eyimpawu ye-pathological ebonakala kwiiyure ze-24-48 emva kwendawo yokulawula i-HA.56
Abanye ababhali bakholelwa ukuba indlela yokusabela ibangelwa kuhlobo lwe-IV hypersensitivity.Inaliti ye-HA yangaphambili yavuselela ukubunjwa kwe-lymphocytes yememori, kunye nokulawulwa okulandelayo kokulungiswa ngokukhawuleza kubangele impendulo yeeseli ze-CD4 + kunye ne-macrophages.39
Isigulane safumana i-prednisolone yomlomo 20-30 mg okanye i-methylprednisolone 16-24 mg imihla ngemihla ngeentsuku ze-5.Emva koko umthamo wancitshiswa ezinye iintsuku ezi-5.Emva kweeveki ezi-2, iimpawu zezigulane ze-10 ezifumene i-oral steroids zanyamalala ngokupheleleyo.Izigulane ezine eziseleyo zaqhubeka zine-edema ephakathi.I-Hyaluronidase isetyenziselwa inyanga enye emva kokuqala kweempawu.39
Ngokutsho kweencwadi, ezininzi iingxaki ezilibazisekile zinokuthi zenzeke emva kokutofa kwe-hyaluronic acid.Nangona kunjalo, umbhali ngamnye wabahlela ngokusekelwe kumava ekliniki.Igama elidityanisiweyo okanye ulwahlulo aluphuhliswanga ukuchaza ezo mpendulo zingalunganga.Igama elithi ngokuqhubekayo intermittent ulibazise ukudumba (PIDS) kwachazwa dermatologists Brazilian ngo 2017. 57 Beleznay et al.yazisa elinye igama ukuchaza le pathology kwi-2015: ukulibaziseka kokuqala kwe-nodule 15,58 kunye ne-Snozzi et al.: i-advanced inflammatory response syndrome (LI).58 Ngo-2020, elinye ixesha lacetywayo: ukulibaziseka ukuvutha kwe-Reaction (DIR).48
Chung et al.wagxininisa ukuba i-DIR ibandakanya iintlobo ezine zokuphendula: 1) i-DTH reaction (ebizwa ngokuchanekileyo: ukulibaziseka uhlobo lwe-IV ye-hypersensitivity reaction);2) ukusabela kwegranuloma yomzimba wangaphandle;3) i-biofilm;4) usulelo lwe-atypical.Ukusabela kwe-DTH kukulibaziseka ukudumba kwe-immune yeselula, okuyimpendulo kwi-allergener.59
Ngokutsho kwemithombo eyahlukeneyo, kunokutshiwo ukuba ukuphindaphinda koku kusabela kuyaguquguquka.Kutshanje kupapashwe iphepha elibhalwe ngabaphandi bakwaSirayeli.Bavavanye inani leziganeko ezimbi ngendlela ye-DIR esekelwe kwi-questionnaire.Uluhlu lwemibuzo lwagcwaliswa ngoogqirha abangama-334 abanikeze iinaliti ze-HA.Iziphumo zibonise ukuba phantse isiqingatha sabantu abazange bafumaneke ukuba bane-DIR, kwaye i-11.4% yaphendula ukuba baye baqaphela le mpendulo ngaphezu kwamaxesha e-5.48 Kuvavanyo lobhaliso lokuvavanya ukhuseleko, iimpendulo ezibangelwe ziimveliso eziveliswe yi-Allergan zibhalwe kakuhle.Emva kokuthatha i-Juvederm Voluma® kwiinyanga ezingama-24, malunga ne-1% yezigulane ze-103 ezibek' esweni zichaze ukusabela okufanayo.I-60 Ngethuba leenyanga ze-68 zokuphononongwa kwe-retrospective yeenkqubo ze-4702, iphethini yokuphendula efanayo yabonwa kwi-0.5% yezigulane.I-Juvederm Voluma® isetyenziswe kwizigulane ze-2342.15 Ipesenti ephezulu yabonwa xa iimveliso zeJuvederm Volbella® zazisetyenziswa kwindawo yeenyembezi kunye nendawo yomlomo.Emva komyinge weeveki ze-8, i-4.25% (n = 17) ineziphindaphindo eziye zafikelela kwiinyanga ze-11 (umyinge we-3.17 episodes).I-42 Uhlalutyo lwakutsha nje lwezigulane ezingaphezu kwewaka ezifumana unyango lwe-Vycross kwi-2-year-up-up kunye ne-fillers lubonise ukuba iziganeko zokulibaziseka kwee-nodules zaziyi-1%.57 Ukuphindaphinda kwempendulo kaChung et al kwingxelo kubaluleke kakhulu.Ngokwezibalo zezifundo ezilindelekileyo, iziganeko zokulibaziseka kwempendulo yokuvuvukala kwaba yi-1.1% ngonyaka, ngelixa kwizifundo zokubuyela emva, kwakungaphantsi kwe-1% ngexesha le-1 ukuya kwi-5.5 iminyaka.Ayizizo zonke iimeko ezixeliweyo ziyi-DIR ngokwenene kuba akukho nkcazo echanekileyo.59
Ukulibaziseka kwempendulo yokuvuvukala (DIR) yesibini ekulawuleni i-tissue filler kwenzeka ubuncinane kwiiveki ezi-2-4 okanye kamva emva kokutofa kwe-HA.I-42 Izibonakaliso zeklinikhi zifana neengqungquthela eziphindaphindiweyo ze-edema eqinile yendawo, ehamba kunye ne-erythema kunye ne-tenderness, okanye i-nodules subcutaneous kwi-HA injection site.42,48 Amaqhuqhuva angafudumala xa ebamba, kwaye ulusu olujikelezileyo lunokuba mfusa okanye lube mdaka.Uninzi lwezigulane zineempendulo kuzo zonke iindawo ngexesha elinye.Kwimeko yokusetyenziswa kwe-HA ngaphambili, kungakhathaliseki ukuba luhlobo luni lokuzalisa okanye inani leenaliti, yinto ebalulekileyo ebonisa ukubonakaliswa kweklinikhi.I-15,39 Izilonda zesikhumba zixhaphake kakhulu kubantu abaye bafaka injected enkulu ye-HA ngaphambili.43 Ukongeza, i-edema ehamba nayo ibonakala kakhulu emva kokuvuka, kwaye iphucula kancinane imini yonke.I-42,44,57 Ezinye izigulane (~ 40%) zineebonakaliso ze-systemic ezifana nomkhuhlane.15
Ezi mpendulo zinokunxulunyaniswa nokungcoliswa kwe-DNA, iprotheni, kunye ne-endotoxin yebhaktheriya, nokuba i-concentration ingaphantsi kakhulu kune-HA.15 Nangona kunjalo, i-LMW-HA isenokubakho kubantu abachaphazeleka ngokwemfuza ngokuthe ngqo okanye ngeemolekyuli ezosulelayo ezinxulumeneyo (ii-biofilms).I-15,44 Nangona kunjalo, ukubonakala kwamaqhuqhuva avuthayo kumgama othile ukusuka kwindawo yokutofa, ukuchasana kwesifo kunyango lwexesha elide lokulwa ne-antibiotic kunye nokukhutshwa kwezifo ezithathelwanayo (inkcubeko kunye novavanyo lwe-PCR)) kuphakamisa ukukrokra malunga nendima ye-biofilms. .Ukongezelela, ukusebenza konyango lwe-hyaluronidase kunye nokuxhomekeka kwidosi ye-HA kubonisa indlela yokulibaziseka kwe-hypersensitivity.42,44
Impendulo ngenxa yokusuleleka okanye ukulimala kunokukhokelela ekunyuseni kwe-serum interferon, enokunyusa ukuvuvukala kwangaphambili.I-15,57,61 Ukongezelela, i-LMW-HA ivuselela i-CD44 okanye i-TLR4 i-receptors ebusweni be-macrophages kunye neeseli ze-dendritic.Iyazivula kwaye ihambise imiqondiso yexabiso kwiiseli ze-T.I-15,19,24 i-nodules evuthayo ehambelana ne-DIR yenzeke kwiinyanga ezi-3 ukuya kwe-5 emva kokutofa kwe-HMW-HA filler (eneempawu ezichasayo), eziye zibole kwaye ziguqule zibe yi-LMW- kunye neepropati ze-HA.15
Ukuqala kokusabela kudla ngokubangelwa yenye inkqubo yosulelo (i-sinusitis, usulelo lwe-urinary tract, usulelo lokuphefumla, usulelo lwamazinyo), ukwenzakala ebusweni, kunye notyando lwamazinyo.57 isiXhosa isiXho Olu tshintsho lwenzeka kwakhona ngenxa yogonyo kwaye lwaphinda lwavela ngenxa yokopha kwasexesheni.I-15, i-57 Isiqendu ngasinye sinokubangelwa yi-infectious triggers.
Abanye ababhali baye bachaza i-genetic predisposition yabantu abanee-subtypes ezilandelayo zokuphendula: i-HLA B * 08 okanye i-DRB1 * 03.4 (ukwanda okuphindwe kane kwingozi).13,62
Izilonda ezinxulumene ne-DIR zibonakaliswa ngamaqhuqhuva avuthayo.Kufuneka zahlulwe kumaqhuqhuva, amathumba (ukuthamba, ukuguquguquka), kunye nokusabela kwegranulomatous (amaqhuqhuva aqinileyo adumbayo) abangelwa ziifilim.58
Chung et al.cebisa ukusebenzisa iimveliso ze-HA zovavanyo lwesikhumba phambi kwenkqubo ecwangcisiweyo, nangona ixesha elifunekayo lokutolika iziphumo zovavanyo linokuba ziiveki ezi-3-4.59 Bacebisa ngokukodwa uvavanyo olunjalo kubantu abaye baba neziganeko ezimbi.Ndiye ndaqaphela ngaphambili.Ukuba uvavanyo luqinisekile, isigulane akufanele siphathwe kwakhona nge-HA filler efanayo.Nangona kunjalo, isenokungaziphelisi zonke iimpendulo kuba zidla ngokubangelwa zizichukumisi, ezifana nosulelo oludibanayo olunokuthi lwenzeke nangaliphi na ixesha.59
Ixesha lokuposa: Sep-28-2021