I-Javascript ivaliwe esipheqululini sakho okwamanje.Uma i-javascript ivaliwe, eminye imisebenzi yale webhusayithi ngeke isebenze.
Bhalisa imininingwane yakho ethile kanye nezidakamizwa ozithakaselayo, futhi sizofanisa ulwazi olunikezayo nama-athikili kusizindalwazi sethu esibanzi futhi sikuthumelele ikhophi ye-PDF nge-imeyili ngesikhathi esifanele.
U-Agnieszka Owczarczyk-Saczonek, Natalia Zdanowska, Ewa Wygonowska, Waldemar Placek Umnyango Wezifo Zesikhumba, Izifo Ezithathelwana Ngocansi kanye Nomtholampilo Wokugonywa Kwamasosha omzimba, Amanyuvesi e-Warmia kanye ne-Mazury e-Olsztyn, Iphephandaba lase-Poland: I-Agnieszka I-Dermatology Department, i-Sexual Diseases Department, i-Imczarczy Clinic, i-Sexual Dermatology I-Warmia ne-Mazury University, i-Olsztyn, ePoland.Wojska Polskiego 30, Olsztyn, 10-229, PolishTel +48 89 6786670 Ifeksi +48 89 6786641 I-imeyili [i-imeyili evikelwe] Abstract: I-Hyaluronic acid (HA) iyi-glycosaminoglycan, isakhi semvelo se-matrix engaphandle kwamaselula.Ukwakheka okufanayo kwe-molecule kuzo zonke izinto eziphilayo kuyinzuzo yayo eyinhloko ngoba inethuba elincane lokuguqulwa libe yi-immunogenicity.Ngakho-ke, ngenxa ye-biocompatibility yayo kanye nokuzinza endaweni yokufakelwa, iyindlela eseduze yokwakhiwa okufanele isetshenziswe njengesigcwalisi.Le ndatshana ifaka phakathi ingxoxo yendlela eyisisekelo yokusabela kokuzivikela komzimba okubi kwe-HA, kanye nendlela yokuphendula ngemva kokugonyelwa i-SARS-CoV-2.Ngokusho kwezincwadi, sizame ukuhlela impendulo engalungile yokuzivikela komzimba ngokubonakaliswa kwesistimu ku-HA.Ukuvela kokusabela okungalindelekile ku-hyaluronic acid kubonisa ukuthi angeke kubhekwe njengokungathathi hlangothi noma okungeyona i-allergenic.Izinguquko ezakhiweni zamakhemikhali e-HA, izithasiselo, kanye nokuthambekela komuntu ngamunye ezigulini kungase kube imbangela yokusabela okungalindelekile, okuholela emiphumeleni emibi yezempilo.Amalungiselelo emvelaphi engaziwa, ukungahlanzeki kahle, noma aqukethe i-DNA yebhaktheriya ayingozi kakhulu.Ngakho-ke, ukulandelwa kwesikhathi eside kweziguli nokukhethwa kwe-FDA noma i-EMA amalungiselelo avunyelwe kubaluleke kakhulu.Iziguli ngokuvamile aziyazi imiphumela yokuhlinzwa okushibhile okwenziwa abantu ngaphandle kolwazi olufanele besebenzisa imikhiqizo engabhalisiwe, ngakho umphakathi kufanele ufundiswe futhi kwethulwe imithetho nemithethonqubo.Amagama angukhiye: I-hyaluronic acid, izigcwalisi, ukuvuvukala okubambezelekile, i-autoimmune/auto-inflammatory adjuvant-induced syndrome, i-SARS-CoV-2
I-Hyaluronic acid (HA) iyi-glycosaminoglycan, isakhi semvelo se-matrix engaphandle kwamaseli.Ikhiqizwa ama-dermal fibroblasts, amaseli e-synovial, amaseli e-endothelial, amaseli emisipha abushelelezi, amaseli e-adventitia nama-oocyte futhi akhishelwa endaweni ezungezile ye-extracellular.I-1,2 Isakhiwo esifanayo sama-molecule kuzo zonke izinto eziphilayo yinzuzo yayo eyinhloko, ehlotshaniswa nengozi encane kakhulu ye-immunogenicity.I-biocompatibility kanye nokuzinza kwesayithi lokufakelwa kuyenza ibe inketho ecishe ifaneleke kulo lonke uchungechunge lokugcwalisa.Ngenxa yokwandiswa komshini kwezicubu ngemva komjovo kanye nokusebenza okwalandela kwe-fibroblasts yesikhumba, kunenzuzo enkulu yokukwazi ukugqugquzela ukukhiqizwa kwe-collagen entsha.I-2-4 Hyaluronic acid ine-hydrophilic ephezulu, inezici ezikhethekile zokubopha ama-molecule amanzi (izikhathi ezingaphezu kuka-1000 isisindo sayo), futhi yakha ukuhambisana okunwetshiwe okunomthamo omkhulu uma kuqhathaniswa nesisindo.Ingase futhi yakhe i-condensation ngisho nasezindaweni eziphansi kakhulu.iglu.Kubangela ukuthi izicubu zisheshe zikhiphe amanzi futhi zikhulise umthamo wesikhumba.I-3,5,6 Ngaphezu kwalokho, umswakama wesikhumba kanye namandla okulwa ne-antioxidant we-hyaluronic acid angakhuthaza ukuvuselelwa kwamangqamuzana esikhumba futhi akhuthaze ukukhiqizwa kwe-collagen.5
Eminyakeni edlule, kuye kwaphawulwa ukuthi ukuthandwa kwezinqubo zezimonyo ezisebenzisa izinto ezifana ne-HA kuye kwaqhubeka kwanda.Ngokwedatha evela ku-International Society of Aesthetic Plastic Surgery (ISAPS), izinqubo zezimonyo ezingaphezu kwezigidi ezingu-4.3 zenziwe kusetshenziswa i-HA ngo-2019, okuwukunyuka ngo-15.7% uma kuqhathaniswa no-2018. I-American Society of Dermatology (ASDS) ibika ukuthi odokotela besikhumba benze u-2.7 million dermal filler injections ngo-2019. 8 Ukuqaliswa kwalezi zinqubo kuba uhlobo olunenzuzo kakhulu lomsebenzi okhokhelwayo.Ngakho-ke, ngenxa yokuntuleka kwemithetho neziqondiso emazweni/ezifundeni eziningi, bayanda abantu abahlinzeka ngezinsizakalo ezinjalo, ngokuvamile ngaphandle kokuqeqeshwa okwanele noma iziqu.Ngaphezu kwalokho, kukhona amafomula ancintisanayo emakethe.Angase abe eshibhile, ekhwalithi ephansi, futhi awagunyazwanga i-FDA noma i-EMA, okuyisici esiyingozi ekuthuthukisweni kwezinhlobo ezintsha zokusabela okungekuhle.Ngokocwaningo olwenziwa eBelgium, iningi lamasampula okusolwa ukuthi angekho emthethweni angu-14 ahloliwe aqukethe imikhiqizo emincane kakhulu kunaleyo eshiwo emaphaketheni.9 Amazwe amaningi anezindawo ezimpunga zezinqubo zezimonyo ezingekho emthethweni.Ngaphezu kwalokho, lezi zinqubo azibhalisiwe futhi azikho izintela ezikhokhwayo.
Ngakho-ke, kunemibiko eminingi yezenzakalo ezimbi ezincwadini.Lezi zehlakalo ezingezinhle ngokuvamile ziholela ekuxilongweni okukhulu nasezinkingeni zokwelashwa kanye nemiphumela engalindelekile ezigulini.I-7,8 Hypersensitivity ku-hyaluronic acid ibaluleke kakhulu.I-pathogenesis yokunye ukusabela ayikacaciswa ngokugcwele, ngakho-ke amagama asezincwadini awafani, futhi ukuvumelana okuningi mayelana nokuphathwa kwezinkinga akukakafaki ukusabela okunjalo.10,11
Lesi sihloko sihlanganisa idatha evela ekubuyekezweni kwezincwadi.Khomba izindatshana zokuhlola ngokusesha i-PubMed usebenzisa imishwana elandelayo: i-hyaluronic acid, izigcwalisi, nemiphumela emibi.Ukusesha kuyaqhubeka kuze kube nguMashi 30, 2021. Kutholwe izindatshana eziyi-105 futhi kwahlaziya ezingama-42 zazo.
I-Hyaluronic acid ayiyona isitho noma uhlobo oluthile, ngakho-ke kungacatshangwa ukuthi ayibangeli ukungezwani komzimba.12 Nokho, kubalulekile ukukhumbula ukuthi umkhiqizo ojovwe uhlanganisa nezithasiselo, futhi i-hyaluronic acid itholakala nge-bacterial biosynthesis.
Kuye kwaboniswa futhi ukuthi ukuthambekela komuntu ngamunye kungaholela engcupheni yokubambezeleka, ukusabela okungalungile kwe-immune-mediated okuhlotshaniswa nama-dermal fillers ezigulini ezithwala ama-haplotype e-HLA-B*08 kanye ne-DR1*03.Le nhlanganisela ye-HLA subtypes ihlotshaniswa nokukhuphuka cishe okuphindwe kane kumathuba okusabela okubi (OR 3.79).13
I-Hyaluronic acid ikhona ngendlela yama-multiparticulate, ukwakheka kwayo kulula, kodwa kuyi-biomolecule esebenzayo.Ubukhulu be-HA buthinta umphumela ophambene: ungase ube nezindawo eziphikisana nokuvuvukala noma eziphikisana nokuvuvukala, ukhuthaze noma uvimbele ukufuduka kwamaseli, futhi wenze kusebenze noma kumise ukuhlukaniswa kwamaseli nokuhlukanisa.14-16 Ngokudabukisayo, akukho ukuvumelana ngokuhlukaniswa kwe-HA.Igama losayizi wamangqamuzana.14,16,17
Uma usebenzisa imikhiqizo ye-HMW-HA, kufanelekile ukukhumbula ukuthi i-hyaluronidase yemvelo idala ukuwohloka kwayo futhi ikhuthaze ukwakheka kwe-LMW-HA.I-HYAL2 (ebambelele kulwelwesi lweseli) ihlukanisa isisindo semolekyuli ephezulu i-HA (>1 MDa) ibe yizingcezu ezingama-20 kDa.Ukwengeza, uma i-HA hypersensitivity iqala, ukuvuvukala kuzokhuthaza ukuwohloka kwayo okuqhubekayo (Umfanekiso 1).
Endabeni yemikhiqizo ye-HA, kungase kube khona umehluko othile ekuchazeni usayizi wamangqamuzana.Isibonelo, eqenjini lemikhiqizo ye-Juvederm (Allergan), ama-molecule > 500 kDa abhekwa njenge-LMW-HA, kanye > 5000 kDa - HMW-HA.Kuzothinta ukwenziwa ngcono kokuphepha komkhiqizo.18
Kwezinye izimo, isisindo esiphansi samangqamuzana (LMW) HA singabangela i-hypersensitivity 14 (Umfanekiso 2).Kubhekwa njenge-molecule ye-pro-inflammatory.Itholakala kakhulu ezindaweni ze-catabolism yezicubu ezisebenzayo, isibonelo, ngemva kokulimala, ibangela ukuvuvukala ngokuthinta ama-Toll-like receptors (TLR2, TLR4).I-14-16,19 Ngale ndlela, i-LMW-HA ikhuthaza ukusebenza nokuvuthwa kwamangqamuzana e-dendritic (DC), futhi ivuselela izinhlobo ezihlukahlukene zamaseli ukuze zikhiqize ama-cytokines a-pro-inflammatory, njenge-IL-1β, IL-6, IL-12 , TNF-α kanye ne-TGF-β, ilawula ukuvezwa kwama-chemokines nokufuduka kwamaseli.14,17,20 I-LMW-HA ingase isebenze njengemodeli ye-molecular ehlobene nengozi (i-DAMP) ukuze iqalise izindlela zokuzivikela ezizalwa nazo, ezifana namaprotheni e-bacterial noma amaprotheni okushisa ukushisa.I-14,21 CD44 isebenza njengendlela yokuqashelwa kwephethini yokwamukela i-LMW-HA.Itholakala phezu kwawo wonke amangqamuzana omuntu futhi ingase ihlanganyele namanye ama-ligand afana ne-osteopontin, i-collagen, ne-matrix metalloproteinases (MMP).14,16,17.
Ngemuva kokuthi ukuvuvukala kuncipha futhi izinsalela zezicubu ezilimele ziqedwa ngama-macrophages, i-molecule ye-LMW-HA isuswa yi-endocytosis encike ku-CD44.Ngokuphambene, ukuvuvukala okungapheli kuhlotshaniswa nokwenyuka kwenani le-LMW-HA, ngakho-ke zingabhekwa njengama-biosensor emvelo wesimo sobuqotho bezicubu.I-14,20,22,23 Indima ye-CD44 receptor ye-HA iboniswe ezifundweni zokulawulwa kokuvuvukala ngaphansi kwezimo ze-vivo.Kumamodeli egundane e-atopic dermatitis, ukwelashwa kwe-anti-CD44 kuvimbela ukuthuthukiswa kwezimo ezifana ne-collagen-induced arthritis noma ukulimala kwesikhumba.amashumi amabili nane
Isisindo samangqamuzana aphezulu (HMW) HA sivamile ezicutshini ezingaqinile.Ivimbela ukukhiqizwa kwama-pro-inflammatory mediators (IL-1β, IL-8, IL-17, TNF-α, metalloproteinases), inciphisa inkulumo ye-TLR futhi ilawula i-angiogenesis.I-14,19 HMW-HA iphinde ithinte umsebenzi wama-macrophages obhekene nokulawulwa ngokugqugquzela umsebenzi wabo wokulwa nokuvuvukala ukuze kuthuthukiswe ukuvuvukala kwendawo.15,24,25
Inani eliphelele le-hyaluronic acid kumuntu onesisindo esingamakhilogremu angu-70 cishe amagremu angu-15, futhi isilinganiso salo sokushintsha isilinganiso singamagremu angu-5 ngosuku.Cishe i-50% ye-hyaluronic acid emzimbeni womuntu igxile esikhumbeni.Ingxenye yempilo yayo ingamahora angama-24-48.I-22,26 Ngakho-ke, isigamu sempilo ye-HA yemvelo engashintshiwe ngaphambi kokuba inqunywe ngokushesha yi-hyaluronidase, ama-enzyme ezicubu zemvelo kanye nezinhlobo ze-oxygen esebenzayo cishe amahora angu-12 kuphela.I-27,28 I-HA chain yathuthukiswa ukuze yandise ukuzinza kwayo futhi ikhiqize ama-molecule amakhulu futhi azinzile, enesikhathi eside sokuhlala esicutshini (cishe izinyanga ezimbalwa), kanye ne-biocompatibility efanayo kanye nezakhiwo zokugcwalisa i-viscoelastic.I-28 Crosslinking ihilela ingxenye ephezulu ye-HA ehlanganisiwe enama-molecule aphansi esisindo samangqamuzana kanye nengxenye ephansi yesisindo se-molecule ephezulu ye-HA.Lokhu kuguqulwa kushintsha ukwakheka kwemvelo kwe-molecule ye-HA futhi kungase kuthinte ukuzivikela kwayo.18
I-Cross-linking ikakhulukazi ihilela ukuxhumanisa ama-polymers ukuze akhe amabhondi ahlangene, ikakhulukazi ahlanganisa (-COOH) kanye/noma ama-hydroxyl (-OH) amathambo.Izinhlanganisela ezithile zingakhuthaza ukuxhumanisa, njenge-1,4-butanediol diglycidyl ether (BDDE) (Juvederm, Restylane, Princess), i-divinyl sulfone (Captique, Hylaform, Prevelle) noma i-diepoxy octane (Puragen).29 Kodwa-ke, amaqembu e-epoxy we-BDDE awashintshile ngemva kokusabela nge-HA, ngakho-ke landelela amanani kuphela we-BDDE engaphenduliwe (<2 izingxenye ngesigidi) angatholakala emkhiqizweni.I-26 i-Cross-linked ha hydrogel iyinto eguquguqukayo kakhulu engaholela ekwakhiweni kwezakhiwo ze-3D ezinezakhiwo eziyingqayizivele (rheology, degradation, applicability).Lezi zici zikhuthaza ukusatshalaliswa kalula komkhiqizo futhi ngesikhathi esifanayo zigqugquzela ukukhiqizwa kwezingxenye zamangqamuzana e-matrix engaphandle kwamaseli.30,31<>
Ukuze kwandiswe i-hydrophilicity yomkhiqizo, abanye abakhiqizi bengeza ezinye izinhlanganisela, njenge-dextran noma i-mannitol.Ngayinye yalezi zithako ingase ibe i-antigen evuselela ukusabela kwamasosha omzimba.
Njengamanje, amalungiselelo e-HA akhiqizwa ezinhlotsheni ezithile ze-Streptococcus ngokusebenzisa ukuvutshelwa kwebhaktheriya.(I-Streptococcus equi noma i-Streptococcus zooepidemicus).Uma kuqhathaniswa namalungiselelo atholakala ezilwaneni asetshenziswe ngaphambilini, kunciphisa ingozi ye-immunogenicity, kodwa ayikwazi ukuqeda ukungcoliswa kwama-molecule amaprotheni, ama-nucleic acids we-bacterial and stabilizers.Angase abe ama-antigen futhi akhuthaze ukusabela kokuzivikela komzimba komsingathi, njengokuzwela ngokweqile emikhiqizweni ye-HA.Ngakho-ke, ubuchwepheshe bokukhiqiza i-filler (njenge-Restylane) bugxile ekwehliseni ukungcoliswa komkhiqizo.32
Ngokomunye umbono, impendulo yokuzivikela komzimba ku-HA ibangelwa ukuvuvukala okubangelwa izingxenye zebhaktheriya ze-biofilm, ezidluliselwa ezicubu lapho umkhiqizo ujova.I-33,34 Biofilm yakhiwe ngamagciwane, izakhi zawo kanye nama-metabolites.Ihlanganisa ikakhulukazi amabhaktheriya angewona ama-pathogenic ahlanganisa isikhumba esinempilo noma ulwelwesi lwamafinyila (isibonelo, i-Dermatobacterium acnes, i-Streptococcus oralis, i-Staphylococcus epidermidis).Lezi Uhlobo luqinisekiswe ukuhlolwa kwe-polymerase chain reaction.33-35
Ngenxa yezici ezihlukile ezikhula kancane kanye nezinhlobonhlobo zazo ezibizwa ngokuthi amakholoni amancane, kuvame ukuba nzima ukukhomba amagciwane esikweni.Ngaphezu kwalokho, i-metabolism yabo ku-biofilm ingase yehliswe, okusiza ukugwema imiphumela yemithi elwa namagciwane.35,36 Ngaphezu kwalokho, amandla okwenza i-matrix engaphandle kwama-polysaccharides e-extracellular (kuhlanganise ne-HA) iyisici sokuvimbela i-phagocytosis.Lawa mabhaktheriya angase ahlale ethule iminyaka eminingi, bese ecushwa izici zangaphandle futhi abangele ukusabela.35-37 Ama-Macrophage namaseli amakhulu ngokuvamile atholakala eduze kwalezi zinambuzane.Zingase zenziwe zisebenze ngokushesha futhi zenze impendulo yokuvuvukala.38 Izinto ezithile, ezifana nokutheleleka kwamagciwane anezinhlobo zebhaktheriya ezifanayo ekwakhekeni kwama-biofilms, zingasebenzisa ama-microorganisms alele ngokusebenzisa izindlela zokulingisa.Ukwenza kusebenze kungase kube ngenxa yomonakalo odalwe enye inqubo yokugcwalisa isikhumba.38
Kunzima ukuhlukanisa phakathi kokuvuvukala nokubambezeleka kwe-hypersensitivity okubangelwa ama-biofilms ebhaktheriya.Uma i-red sclerotic lesion ibonakala nganoma isiphi isikhathi ngemva kokuhlinzwa, kungakhathaliseki ubude besikhathi, i-biofilm kufanele isolwe ngokushesha.38 Ingase ibe yi-asymmetrical futhi ilingane, futhi ngezinye izikhathi ingase ithinte zonke izindawo lapho i-HA inikezwa khona ngesikhathi sokuhlinzwa.Ngisho noma umphumela wesiko ungalungile, isibulala-magciwane esine-spectrum esibanzi esingena kahle esikhumbeni kufanele sisetshenziswe.Uma kukhona ama-fibrous nodules anokumelana okwandayo, kungenzeka kube i-granuloma yomzimba wangaphandle.
I-HA ingase futhi ikhuthaze ukuvuvukala ngokusebenzisa indlela yama-superantigens.Le mpendulo ayidingi izigaba zokuqala zokuvuvukala.Ama-Superantigen angu-12,39 aqala u-40% wamaseli e-T okuqala futhi ngokunokwenzeka nokuvula i-clonal ye-NKT.Ukusebenza kwalawa ma-lymphocyte kuholela esivunguvungwini se-cytokine, esibonakala ngokukhululwa kwenani elikhulu lama-cytokines ane-pro-inflammatory, njenge-IL-1β, IL-2, IL-6 ne-TNF-α40.
I-pneumonia enzima, evame ukuhambisana nokuhluleka kokuphefumula okukhulu, iyisibonelo sokusabela kwe-pathological ku-superantigen ye-bacterial (staphylococcal enterotoxin B), okwandisa i-LMW-HA ekhiqizwa ama-fibroblasts ezicutshini zamaphaphu.I-HA igqugquzela ukukhiqizwa kwe-IL-8 kanye ne-IP-10 chemokines, edlala indima ebalulekile ekubutheni amangqamuzana avuvukalayo emaphashini.I-40,41 Izindlela ezifanayo ziye zabonwa phakathi ne-asthma, isifo esingapheli se-pulmonary obstructive pulmonary kanye ne-pneumonia.Ukukhiqizwa okwandayo kwe-COVID-19.41 LMW-HA kuholela ekuvuthweni ngokweqile kwe-CD44 kanye nokukhululwa kwama-cytokines nama-chemokines abangela ukuvuvukala.40 Lo mshini ungabuye ubonwe ekuvuvukeni okubangelwa izingxenye ze-biofilm.
Lapho ubuchwepheshe bokukhiqiza i-filler bebunganembe kangako ngo-1999, ubungozi bokubambezeleka kokusabela ngemuva komjovo we-HA kwanqunywa ukuthi bungu-0.7%.Ngemuva kokwethulwa kwemikhiqizo ehlanzekile, izehlakalo zezehlakalo ezimbi ezinjalo zehle zaba ngu-0.02%.3,42,43 Nokho, ukwethulwa kwama-HA fillers ahlanganisa amaketanga e-HA aphezulu naphansi kubangele amaphesenti aphezulu e-AE.44
Idatha yokuqala mayelana nokusabela okunjalo ivele embikweni wokusetshenziswa kwe-NASHA.Lokhu ukusabela kwe-erythema kanye ne-edema, ngokungenwa kanye ne-edema endaweni ezungezile ehlala izinsuku ezingu-15.Lokhu kusabela kubonwe esigulini esisodwa kwezingu-1400.3 Abanye ababhali babike izigaxana ezivuthayo ezihlala isikhathi eside, ezenzeka ku-0.8% weziguli.45 Bagcizelela i-etiology ehlobene nokungcoliswa kwamaprotheni okubangelwa ukuvutshelwa kwamagciwane.Ngokusho kwezincwadi, imvamisa yokusabela okubi yi-0.15-0.42%.3,6,43
Endabeni yokusebenzisa indinganiso yesikhathi, kunemizamo eminingi yokuhlukanisa imiphumela emibi ye-HA.46
Bitterman-Deutsch et al.ihlukanise izimbangela zokusabela okubi kanye nezinkinga ngemuva kokuhlinzwa ngamalungiselelo asuselwa ku-hyaluronic acid.Zihlanganisa
Iqembu lochwepheshe lazama ukuchaza impendulo ku-hyaluronic acid esekelwe esikhathini sokubukeka ngemva kokuhlinzwa: "ekuqaleni" (<14 izinsuku), "sekwephuzile" (> Izinsuku ezingu-14 kuya ku-1 unyaka) noma "ibambezelekile" (> 1 ngonyaka).47-49 Abanye ababhali bahlukanise impendulo yaba kusenesikhathi (kuze kufike evikini elilodwa), okumaphakathi (ubude besikhathi: isonto elilodwa ukuya enyangeni eyodwa), kanye nekwephuzile (ngaphezu kwenyanga eyodwa).50 Njengamanje, izimpendulo ezifike sekwephuzile nezibambezelekile zibhekwa njengebhizinisi elilodwa, elibizwa ngokuthi ukusabela kokuvuvukala okulibazisekayo (DIR), ngoba izimbangela zazo ngokuvamile azichazwa ngokucacile futhi ukwelashwa akuhlobene nembangela.42 Ukuhlukaniswa kwalokhu kusabela kungahlongozwa ngokusekelwe ezincwadini (Umfanekiso 3).
I-edema yesikhashana endaweni yomjovo ngokushesha ngemva kokuhlinzwa ingase ibe ngenxa yendlela yokukhishwa kwe-histamine ezigulini ezithambekele ekuthini zingezwani nohlobo 1, ikakhulukazi lezo ezinomlando wezifo zesikhumba.51 Kuyimizuzu embalwa nje ngemva kokuphathwa lapho ama-mast cells alinyazwa ngomshini futhi akhulule abalamuli ababangela ukuvuvukala ukuze kubangele i-tissue edema kanye nokwakheka kwenqwaba yomoya.Uma impendulo ehilela ama-mast cells kwenzeka, inkambo yokwelashwa kwe-antihistamine ngokuvamile yanele.51
Umonakalo omkhulu wesikhumba obangelwa ukuhlinzwa kwezimonyo, i-edema enkulu, engase iqhubekele ku-10-50%.52 Ngokusho kwedayari yeziguli ezinezimpumputhe eziphindwe kabili ezingaboni ngaso linye, imvamisa ye-edema ngemuva komjovo we-Restylane ilinganiselwa ku-87% wocwaningo 52,53.
Izindawo ezisebusweni ezibonakala zithandwa kakhulu yi-edema yizindebe, izindawo ze-periorbital nezihlathini.52 Ukuze unciphise ingozi, kunconywa ukugwema ukusetshenziswa kwenani elikhulu lama-fillers, i-anesthesia yokungena, i-massage esebenzayo kanye namalungiselelo e-hygroscopic kakhulu.Izithasiselo (i-mannitol, i-dextran).52
I-Edema endaweni yomjovo ehlala imizuzu embalwa kuya ezinsukwini ezingu-2-3 ingase ibangelwe yi-hygroscopicity ye-HA.Lokhu kusabela kuvame ukubonwa endaweni ye-perilip kanye ne-periorbital.I-49,54 akufanele yenze iphutha nge-edema ebangelwa indlela engavamile kakhulu yokusabela ngokushesha komzimba (i-angioedema).49
Ngemuva komjovo we-Restylane (NASHA) odebeni olungaphezulu, kwachazwa icala lokuzwela ku-angioedema.Kodwa-ke, isiguli siphinde sathatha i-lidocaine engu-2%, engase futhi iqalise ukusabela kwe-hypersensitivity yohlobo lwe-I.Ukuphathwa okuhlelekile kwe-corticosteroids kubangele ukuthi i-edema iphele phakathi nezinsuku ezi-4.32
Ukusabela okuguqukayo ngokushesha kungase kube ngenxa yokuzwela ngokweqile ekungcolisweni kwensalela yamaprotheni ye-HA synthesizing bacteria.Ukusebenzisana phakathi kwe-HA ejovwe kanye namaseli e-mast asele ku-tissue kungenye indlela yokucacisa isenzo sokuphendula ngokushesha.I-CD44 receptor endaweni yama-mast cells iyisamukeli se-HA, futhi lokhu kusebenzisana kungase kubaluleke ekufudukeni kwawo.32,55
Ukwelashwa kuhlanganisa ukuphathwa ngokushesha kwama-antihistamine, i-systemic GCS, noma i-epinephrine.46
Umbiko wokuqala, oshicilelwe nguTurkmani et al., Uchaze abesifazane abaneminyaka engu-22-65 ababehlinzwe i-HA ekhiqizwa izinkampani ezahlukene.39 Izilonda zesikhumba zibonakaliswa yi-erythema kanye ne-edema ebuhlungu endaweni yomjovo wokugcwalisa ebusweni.Kuzo zonke izimo, impendulo iqala ezinsukwini ezingu-3-5 ngemva kokugula okufana nomkhuhlane (umkhuhlane, ikhanda elibuhlungu, umphimbo obuhlungu, ukukhwehlela, nokukhathala).Ngaphezu kwalokho, zonke iziguli zazithole ukuphathwa kwe-HA (izikhathi ezi-2 kuye kweziyi-6) eminyakeni emi-4 ngaphambi kokuba izimpawu zivele ezingxenyeni ezihlukene zobuso.39
Isethulo somtholampilo sokusabela okuchaziwe (i-erythema ne-edema noma ukuqubuka okufana ne-urticaria nokubonakala kwesistimu) kufana nokusabela kohlobo lwe-III-ukusabela kokugula kwe-pseudoserum.Ngeshwa, ayikho imibiko ezincwadini eqinisekisa le mbono.Umbiko wecala uchaza isiguli esine-rash-like lesion ngesikhathi se-Sweet syndrome, okuyisibonakaliso se-pathological esivela emahoreni angu-24-48 ngemva kwesayithi lokuphatha le-HA.56
Abanye ababhali bakholelwa ukuthi indlela yokusabela ibangelwa uhlobo lwe-IV hypersensitivity.Umjovo wangaphambilini we-HA ukhuthaze ukwakheka kwama-lymphocyte enkumbulo, futhi ukuphathwa okwalandela kokulungiselela kwaqala ngokushesha ukusabela kwamaseli e-CD4 + nama-macrophages.39
Isiguli sathola i-prednisolone yomlomo 20-30 mg noma i-methylprednisolone 16-24 mg nsuku zonke izinsuku ezingu-5.Khona-ke umthamo wehliswa ezinye izinsuku ezingu-5.Ngemuva kwamaviki ama-2, izimpawu zeziguli eziyi-10 ezathola i-oral steroids zanyamalala ngokuphelele.Iziguli ezine ezisele zaqhubeka nokuba ne-edema encane.I-Hyaluronidase isetshenziswa inyanga eyodwa ngemuva kokuqala kwezimpawu.39
Ngokusho kwezincwadi, izinkinga eziningi ezibambezelekile zingase zenzeke ngemva kokujova i-hyaluronic acid.Nokho, umbhali ngamunye uzihlukanise ngokusekelwe kokuhlangenwe nakho komtholampilo.Itemu elihlanganisiwe noma ukuhlukaniswa akuzange kuthuthukiswe ukuchaza ukusabela okubi okunjalo.Itemu elithi continuous intermittent delayed swelling (PIDS) lichazwe odokotela besikhumba base-Brazilian ngo-2017. 57 Beleznay et al.yethule elinye igama elichaza lesi sifo ngo-2015: ukubambezeleka kokuqala kwe-nodule 15,58 kanye no-Snozzi et al.: i-advanced inflammatory response syndrome (LI).58 Ngo-2020, elinye igama lahlongozwa: Ukusabela kokuvuvukala okubambezelekile (DIR).48
Chung et al.ugcizelele ukuthi i-DIR ihlanganisa izinhlobo ezine zokusabela: 1) Ukusabela kwe-DTH (okubizwa kahle: ukulibaziseka kohlobo lwe-IV hypersensitivity reaction);2) ukusabela komzimba we-granuloma wangaphandle;3) i-biofilm;4) ukutheleleka kwe-atypical.Ukusabela kwe-DTH wukuvuvukala kweselula okubambezelekile, okuyimpendulo kuma-allergener.59
Ngokwemithombo ehlukene, kungashiwo ukuthi imvamisa yalokhu kusabela iyahlukahluka.Muva nje kushicilelwe iphepha elibhalwe abacwaningi bakwa-Israel.Bahlole inani lezehlakalo ezimbi ngendlela ye-DIR ngokusekelwe kuhlu lwemibuzo.Uhlu lwemibuzo lwagcwaliswa ngodokotela abangama-334 abanikeze imijovo ye-HA.Imiphumela ibonise ukuthi cishe ingxenye yabantu ayizange itholakale ne-DIR, futhi i-11.4% iphendule ukuthi ibone lokhu kusabela izikhathi ezingaphezu kwezingu-5.48 Ekuhlolweni kokubhalisa ukuhlola ukuphepha, ukusabela okubangelwa imikhiqizo ekhiqizwe yi-Allergan kubhalwe kahle.Ngemva kokuthatha i-Juvederm Voluma® izinyanga ezingu-24, cishe i-1% yeziguli ezingu-103 ezaziqashwe zabika ukusabela okufanayo.I-60 Phakathi nokubuyekezwa okuphindaphindiwe kwezinyanga ze-68 kwezinqubo ze-4702, iphethini yokuphendula efanayo yabonwa ku-0.5% yeziguli.IJuvederm Voluma® isetshenziswe ezigulini ezingama-2342.15 Amaphesenti aphezulu abonwa lapho imikhiqizo ye-Juvederm Volbella® isetshenziswa endaweni yezinyembezi nendawo yomlomo.Ngemva kwesilinganiso samaviki angu-8, u-4.25% (n=17) ube nokuphindaphinda okuhlala kuze kufike ezinyangeni eziyi-11 (isilinganiso seziqephu ezingu-3.17).42 Ukuhlaziywa kwakamuva kweziguli ezingaphezu kwenkulungwane ezithola ukwelashwa kwe-Vycross kokulandelwa kweminyaka emi-2 ngama-filler kubonise ukuthi izehlakalo zokubambezeleka kwamanodule zazingu-1%.57 Imvamisa yokuphendula kukaChung et al. embikweni ibaluleke kakhulu.Ngokwezibalo zezifundo ezizokwenzeka, izehlakalo zokubambezeleka kokuphendula kokuvuvukala kwaba ngu-1.1% ngonyaka, kuyilapho ezifundweni ezibukwayo, zazingaphansi kwe-1% phakathi nenkathi ye-1 kuya ku-5.5 iminyaka.Akuwona wonke amacala abikiwe empeleni angama-DIR ngoba ayikho incazelo enembile.59
Ukusabela kokuvuvukala okubambezelekile (DIR) okwesibili ekuphathweni kokugcwalisa izicubu kwenzeka okungenani amasonto angu-2-4 noma kamuva ngemva komjovo we-HA.I-42 Ukubonakaliswa komtholampilo kusesimweni seziqephu eziphindaphindiwe ze-edema eqinile yendawo, ehambisana ne-erythema kanye nesisa, noma ama-nodule angaphansi kwesikhumba endaweni yomjovo we-HA.42,48 Amaqhuqhuva angase afudumale lapho uwathinta, futhi isikhumba esizungezile singaba nsomi noma sibe nsundu.Iziguli eziningi zinokusabela kuzo zonke izingxenye ngesikhathi esisodwa.Endabeni yokusebenzisa i-HA ngaphambili, kungakhathaliseki ukuthi hlobo luni lwesigcwalisi noma inombolo yomjovo, kuyisici esibalulekile esibonisa ukubonakaliswa komtholampilo.Izilonda zesikhumba ezingu-15,39 zivame kakhulu kubantu abake bajova amanani amakhulu e-HA.43 Ngaphezu kwalokho, i-edema ehambisana nayo ibonakala kakhulu ngemva kokuvuka, futhi iba ngcono kancane usuku lonke.42,44,57 Ezinye iziguli (~40%) zinokubonakaliswa okuhambisana nomkhuhlane wesistimu.15
Lokhu kusabela kungase kuhlotshaniswe nokungcoliswa kwe-DNA, amaprotheni, ne-endotoxin yebhaktheriya, noma ngabe ukugxila kuphansi kakhulu kunalokho kwe-HA.15 Kodwa-ke, i-LMW-HA ingase ibe khona kubantu abathintekayo ngokofuzo ngokuqondile noma ngama-molecule athathelwanayo ahlobene (ama-biofilms).I-15,44 Nokho, ukubonakala kwamaqhuqhuva avuthayo ebangeni elithile ukusuka endaweni yomjovo, ukumelana nesifo ekwelapheni isikhathi eside kwama-antibiotic kanye nokukhishwa kwezifo ezithathelwanayo (isiko kanye nokuhlolwa kwe-PCR)) kuphakamisa izinsolo mayelana nendima yama-biofilms. .Ngaphezu kwalokho, ukuphumelela kokwelashwa kwe-hyaluronidase kanye nokuncika kumthamo we-HA kubonisa indlela yokubambezeleka kwe-hypersensitivity.42,44
Ukusabela ngenxa yokutheleleka noma ukulimala kungaholela ekwandeni kwe-serum interferon, okungase kukhulise ukuvuvukala okukhona ngaphambili.15,57,61 Ngaphezu kwalokho, i-LMW-HA ivuselela ama-CD44 noma ama-TLR4 receptors ebusweni bama-macrophages namaseli e-dendritic.Iwenza asebenze futhi ilethe amasignali e-costimulatory kuma-T cell.15,19,24 Izigaxana ezivuthayo ezihambisana ne-DIR zenzeka phakathi nezinyanga ezingu-3 kuya kwezingu-5 ngemva kokujova isigcwalisi se-HMW-HA (enezici zokulwa nokuvuvukala), ebese ibola futhi iguqule ibe yi-LMW- enezici ezivimbela ukuvuvukala i-HA.15
Ukuqala kokusabela kuvame ukuvuswa enye inqubo yokutheleleka (i-sinusitis, ukutheleleka komgudu womchamo, izifo zokuphefumula, izifo zamazinyo), ukulimala ebusweni, nokuhlinzwa kwamazinyo.57 Lokhu kusabela kwabangelwe ukugoma futhi kwaphindeka ngenxa yokopha kokuya esikhathini.15, 57 Isiqephu ngasinye singase sidalwe izibangeli ezithathelwanayo.
Abanye ababhali baye bachaza i-genetic predisposition yabantu abanalezi zinhlobo ezilandelayo zokuphendula: I-HLA B * 08 noma i-DRB1 * 03.4 (ukwanda kwengozi okuphindwe kane).13,62
Izilonda ezihlobene ne-DIR zibonakala ngama-nodules avuthayo.Kufanele ahlukaniswe namaqhuqhuva, amathumba (ukuthamba, ukuguquguquka), kanye nokusabela kwe-granulomatous (amaqhuqhuva aqinile okuvuvukala) okubangelwa ama-biofilms.58
Chung et al.phakamisa ukusebenzisa imikhiqizo ye-HA yokuhlolwa kwesikhumba ngaphambi kwenqubo ehleliwe, nakuba isikhathi esidingekayo sokuhumusha imiphumela yokuhlolwa singase sibe amasonto angu-3-4.59 Batusa ngokukhethekile ukuhlolwa okunjalo kubantu abaye baba nezigigaba ezimbi.Ngike ngaqaphela ngaphambili.Uma ukuhlolwa ku-positive, isiguli akufanele siphinde selashwe ngesigcwalisi se-HA esifanayo.Kodwa-ke, kungase kungakuqedi konke ukusabela ngoba ngokuvamile kubangelwa izinto ezibangisayo, njengezifo ezihambisanayo ezingase zenzeke noma nini.59
Isikhathi sokuthumela: Sep-28-2021