Immunogenicity thiab qhov tshwm sim ntawm hyaluronic acid fillers

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Sau npe rau koj cov ntsiab lus tshwj xeeb thiab cov tshuaj tshwj xeeb uas txaus siab, thiab peb yuav phim cov ntaub ntawv koj muab nrog cov ntawv hauv peb cov ntaub ntawv dav dav thiab xa koj daim ntawv PDF ntawm email raws sijhawm.
Agnieszka Owczarczyk-Saczonek, Natalia Zdanowska, Ewa Wygonowska, Waldemar Placek Department of Dermatology, Cov Kab Mob Sib Cuam Sib Cuam thiab Kev Tshuaj Tiv Thaiv Kab Mob, Warmia thiab Mazury Universities hauv Olsztyn, Poland Cov Ntawv Xov Xwm: Agnieszka Owczarcmittedology, Department of Sex Warmia thiab Mazury University, Olsztyn, Poland.Wojska Polskiego 30, Olsztyn, 10-229, PolishTel +48 89 6786670 Fax +48 89 6786641 Email [email tiv thaiv] Abstract: Hyaluronic acid (HA) yog glycosaminoglycan, ib tug natural tivthaiv ntawm lub extracellular.Tib cov qauv ntawm cov molecule nyob rau hauv tag nrho cov kab mob yog nws lub ntsiab kom zoo dua vim hais tias nws muaj tsawg tshaj plaws tau ntawm hloov mus rau hauv immunogenicity.Yog li ntawd, vim nws biocompatibility thiab stability ntawm qhov chaw implantation, nws yog qhov zoo tshaj plaws formulation uas yuav siv los ua ib tug muab tub lim.Kab lus no suav nrog kev sib tham txog lub hauv paus txheej txheem ntawm HA cov tshuaj tiv thaiv kab mob tsis zoo, nrog rau cov txheej txheem teb tom qab txhaj tshuaj tiv thaiv SARS-CoV-2.Raws li cov ntaub ntawv, peb tau sim ua kom lub cev tiv thaiv kab mob tsis zoo nrog cov kab mob tshwm sim hauv HA.Qhov tshwm sim ntawm qhov tshwm sim tsis tau tshwm sim rau hyaluronic acid qhia tau tias lawv yuav tsis raug suav hais tias yog nruab nrab lossis tsis ua xua.Kev hloov pauv hauv HA cov qauv tshuaj, tshuaj ntxiv, thiab kev nyiam ntawm tus kheej hauv cov neeg mob tuaj yeem ua rau muaj kev cuam tshuam tsis zoo, ua rau muaj kev mob nkeeg loj.Kev npaj tsis paub keeb kwm, kev ua kom huv tsis zoo, lossis muaj cov kab mob DNA yog qhov txaus ntshai tshwj xeeb.Yog li ntawd, kev soj ntsuam mus sij hawm ntev ntawm cov neeg mob thiab xaiv FDA lossis EMA kev pom zoo npaj yog qhov tseem ceeb heev.Cov neeg mob feem ntau tsis paub txog qhov tshwm sim ntawm kev ua haujlwm pheej yig dua ua los ntawm cov neeg uas tsis muaj kev paub txog kev siv cov khoom lag luam uas tsis tau sau npe, yog li cov pej xeem yuav tsum tau kawm thiab cov kev cai lij choj yuav tsum tau qhia.Keywords: Hyaluronic acid, fillers, qeeb o, autoimmune/auto-inflammatory adjuvant-induced syndrome, SARS-CoV-2
Hyaluronic acid (HA) yog ib tug glycosaminoglycan, ib tug natural tivthaiv ntawm extracellular matrix.Nws yog tsim los ntawm dermal fibroblasts, synovial hlwb, endothelial hlwb, du nqaij hlwb, adventitia hlwb thiab oocytes thiab tso tawm mus rau hauv ib ncig ntawm extracellular chaw.1,2 Cov qauv tib yam ntawm cov molecules nyob rau hauv tag nrho cov kab mob yog nws lub ntsiab kom zoo dua, uas yog txuam nrog qhov tsawg tshaj plaws kev pheej hmoo ntawm immunogenicity.Lub biocompatibility thiab ruaj khov ntawm qhov chaw cog qoob loo ua rau nws yog qhov kev xaiv zoo tshaj plaws rau tag nrho cov muab tub lim.Vim tias cov neeg kho tshuab nthuav dav ntawm cov ntaub so ntswg tom qab txhaj tshuaj thiab tom qab ua kom cov tawv nqaij fibroblasts, nws muaj qhov zoo ntawm kev muaj peev xwm txhawb kev tsim cov collagen tshiab.2-4 Hyaluronic acid yog hydrophilic heev, muaj cov yam ntxwv tshwj xeeb ntawm kev khi dej molecules (ntau tshaj 1000 npaug ntawm nws tus kheej qhov hnyav), thiab ua kom muaj kev sib txuas ntxiv nrog lub ntim loj piv rau qhov hnyav.Nws tuaj yeem tsim condensation txawm nyob rau hauv tsawg heev concentrations.kua nplaum.Nws ua rau cov ntaub so ntswg sai sai hydrate thiab nce qhov ntim ntawm daim tawv nqaij.3,5,6 Tsis tas li ntawd, daim tawv nqaij moisturizing thiab antioxidant muaj peev xwm ntawm hyaluronic acid tuaj yeem txhawb cov tawv nqaij rov tsim dua tshiab thiab txhawb kev tsim collagen.5
Tau ntau xyoo, nws tau pom tias qhov nrov ntawm cov txheej txheem tshuaj pleev ib ce siv cov tshuaj xws li HA tau nce ntxiv.Raws li cov ntaub ntawv los ntawm International Society of Aesthetic Plastic Surgery (ISAPS), ntau dua 4.3 lab cov txheej txheem kho kom zoo nkauj tau ua tiav siv HA hauv 2019, nce ntawm 15.7% piv rau 2018. American Society of Dermatology (ASDS) qhia tias cov kws kho mob dermatologist tau ua 2.7. lab txhaj tshuaj dermal dermal hauv 2019. 8 Kev ua raws li cov txheej txheem no tau dhau los ua ib qho txiaj ntsig zoo ntawm cov haujlwm them nyiaj.Yog li ntawd, vim tsis muaj kev cai lij choj thiab kev tswj hwm hauv ntau lub tebchaws / cheeb tsam, ntau thiab ntau tus neeg muab cov kev pabcuam zoo li no, feem ntau tsis muaj kev cob qhia lossis kev tsim nyog.Tsis tas li ntawd, muaj kev sib tw formulations ntawm kev ua lag luam.Tej zaum lawv yuav pheej yig dua, tsis zoo, thiab tsis tau txais kev pom zoo los ntawm FDA lossis EMA, uas yog ib qho kev pheej hmoo rau kev loj hlob ntawm hom tshiab ntawm kev tsis zoo.Raws li kev tshawb fawb hauv Belgium, feem ntau ntawm 14 qhov xav tias tsis raug cai kuaj kuaj muaj cov khoom lag luam tsawg dua li teev nyob rau hauv lub ntim.9 Ntau lub teb chaws muaj qhov grey ntawm cov txheej txheem pleev xim tsis raug cai.Tsis tas li ntawd, cov txheej txheem no tsis tau sau npe thiab tsis muaj se them se.
Yog li ntawd, muaj ntau cov lus ceeb toom ntawm cov xwm txheej tsis zoo hauv cov ntaub ntawv.Cov xwm txheej tsis zoo no feem ntau ua rau muaj kev kuaj mob ntau thiab kho cov teeb meem thiab qhov tshwm sim tsis zoo rau cov neeg mob.7,8 Hypersensitivity rau hyaluronic acid yog qhov tseem ceeb tshwj xeeb.Lub pathogenesis ntawm qee qhov kev tshwm sim tsis tau qhia meej meej, yog li cov lus siv hauv cov ntaub ntawv tsis sib xws, thiab ntau qhov kev pom zoo ntawm kev tswj cov teeb meem tseem tsis tau suav nrog cov kev cuam tshuam no.10,11 ib
Tsab ntawv no suav nrog cov ntaub ntawv los ntawm kev tshuaj xyuas cov ntaub ntawv.Txheeb xyuas cov ntawv ntsuam xyuas los ntawm kev tshawb nrhiav PubMed siv cov lus hauv qab no: hyaluronic acid, fillers, thiab phiv.Kev tshawb nrhiav txuas ntxiv mus txog thaum Lub Peb Hlis 30, 2021. Pom 105 tshooj thiab txheeb xyuas 42 ntawm lawv.
Hyaluronic acid tsis yog lub cev lossis hom tshwj xeeb, yog li nws tuaj yeem xav tias nws tsis ua rau muaj kev fab tshuaj.12 Txawm li cas los xij, nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias cov khoom txhaj tshuaj kuj muaj cov tshuaj ntxiv, thiab hyaluronic acid tau txais los ntawm cov kab mob biosynthesis.
Nws kuj tau pom tias tus neeg muaj peev xwm tuaj yeem ua rau muaj kev pheej hmoo qeeb, kev tiv thaiv kev tiv thaiv kab mob tsis zoo cuam tshuam nrog cov kab mob dermal hauv cov neeg mob nqa HLA-B * 08 thiab DR1 * 03 haplotypes.Qhov kev sib xyaw ua ke ntawm HLA subtypes yog txuam nrog yuav luag plaub npaug ntawm qhov muaj feem cuam tshuam tsis zoo (OR 3.79).13
Hyaluronic acid muaj nyob rau hauv daim ntawv ntawm multiparticulates, nws tsim yog yooj yim, tab sis nws yog ib tug multifunctional biomolecule.Qhov loj ntawm HA cuam tshuam qhov cuam tshuam rau qhov tsis sib xws: nws yuav muaj cov khoom tiv thaiv kab mob lossis tiv thaiv kab mob, txhawb lossis inhibit cell migration, thiab qhib lossis nres ntawm tes faib thiab sib txawv.14-16 Tu siab kawg, tsis muaj kev pom zoo ntawm kev sib cais ntawm HA.Lub sij hawm rau molecular loj.14, 16, 17, ib
Thaum siv HMW-HA cov khoom, nws tsim nyog nco ntsoov tias ntuj hyaluronidase ua rau nws degradation thiab txhawb kev tsim ntawm LMW-HA.HYAL2 (anchored rau ntawm cell membrane) cleaves siab molecular hnyav HA (> 1 MDa) rau hauv 20 kDa fragments.Tsis tas li ntawd, yog HA hypersensitivity pib, o yuav txhawb nqa nws ntxiv degradation (Daim duab 1).
Nyob rau hauv cov ntaub ntawv ntawm HA cov khoom, tej zaum yuav muaj ib co txawv nyob rau hauv lub txhais ntawm molecular loj.Piv txwv li, rau ib pawg ntawm Juvederm cov khoom (Allergan), molecules> 500 kDa raug suav hais tias yog LMW-HA, thiab> 5000 kDa - HMW-HA.Nws yuav cuam tshuam rau kev txhim kho cov khoom ruaj ntseg.18
Qee zaum, qhov hnyav molecular (LMW) HA tuaj yeem ua rau muaj qhov tsis haum 14 (Daim duab 2).Nws yog suav hais tias yog ib tug pro-inflammatory molecule.Nws muaj ntau nyob rau hauv cov ntaub so ntswg catabolism qhov chaw, piv txwv li, tom qab raug mob, nws ua rau mob los ntawm kev cuam tshuam rau tus xov tooj hu ua receptors (TLR2, TLR4).14-16,19 Nyob rau hauv no txoj kev, LMW-HA txhawb kev ua kom thiab maturation ntawm dendritic hlwb (DC), thiab txhawb ntau hom hlwb los tsim pro-inflammatory cytokines, xws li IL-1β, IL-6, IL-12. , TNF-α thiab TGF-β, tswj kev qhia ntawm chemokines thiab cell migration.14,17,20 LMW-HA tuaj yeem ua raws li cov qauv kev phom sij ntsig txog molecular (DAMP) los pib lub cev tiv thaiv kab mob, zoo ib yam li cov kab mob proteins lossis cov protein ua kom sov.14,21 CD44 ua haujlwm raws li daim ntawv ntawm kev lees paub tus qauv rau LMW-HA.Nws muaj nyob rau ntawm tag nrho cov tib neeg lub hlwb thiab yuav cuam tshuam nrog lwm cov ligands xws li osteopontin, collagen, thiab matrix metalloproteinases (MMP).14, 16, 17, ib.
Tom qab qhov mob tshwm sim thiab cov seem ntawm cov ntaub so ntswg raug tshem tawm los ntawm macrophages, LMW-HA molecule raug tshem tawm los ntawm CD44-dependent endocytosis.Hauv qhov sib piv, qhov mob ntev yog cuam tshuam nrog qhov nce ntawm LMW-HA, yog li lawv tuaj yeem suav tias yog ntuj biosensors ntawm cov ntaub so ntswg ncaj ncees.14,20,22,23 Lub luag hauj lwm ntawm CD44 receptor ntawm HA tau pom nyob rau hauv cov kev tshawb fawb ntawm kev tswj ntawm o nyob rau hauv vivo tej yam kev mob.Hauv nas qauv ntawm atopic dermatitis, anti-CD44 kev kho mob inhibits kev loj hlob ntawm cov mob xws li collagen-induced mob caj dab los yog daim tawv nqaij puas.nees nkaum plaub
Qhov hnyav molecular hnyav (HMW) HA muaj ntau nyob rau hauv cov ntaub so ntswg.Nws inhibits zus tau tej cov pro-inflammatory mediators (IL-1β, IL-8, IL-17, TNF-α, metalloproteinases), txo TLR qhia thiab tswj angiogenesis.14,19 HMW-HA kuj tseem cuam tshuam rau kev ua haujlwm ntawm macrophages lub luag haujlwm rau kev tswj hwm los ntawm kev txhawb nqa lawv cov kev tiv thaiv kab mob los txhim kho kev mob hauv zos.15, 24, 25 ib
Tag nrho cov nyiaj ntawm hyaluronic acid nyob rau hauv ib tug neeg hnyav 70 kg yog hais txog 15 grams, thiab nws qhov nruab nrab turnover tus nqi yog 5 grams ib hnub twg.Kwv yees li 50% ntawm hyaluronic acid nyob rau hauv tib neeg lub cev yog concentrated nyob rau hauv daim tawv nqaij.Nws ib nrab-lub neej yog 24-48 teev.22,26 Yog li ntawd, ib nrab-lub neej ntawm unmodified natural HA ua ntej nws yog sai cleaved los ntawm hyaluronidase, tej yam ntuj tso cov ntaub so ntswg enzymes thiab reactive oxygen hom tsuas yog hais txog 12 teev.27,28 Cov saw hlau HA tau tsim los ua kom nws ruaj khov thiab tsim cov molecules loj dua thiab ruaj khov, nrog lub sijhawm nyob ntev dua hauv cov ntaub so ntswg (txog ob peb lub hlis), thiab nrog cov biocompatibility zoo sib xws thiab viscoelastic filling zog.28 Crosslinking muaj feem ntau dua ntawm kev sib xyaw HA nrog cov molecular hnyav molecules thiab qis dua ntawm qhov hnyav molecular HA.Qhov kev hloov kho no hloov lub ntuj tsim ntawm HA molecule thiab tej zaum yuav cuam tshuam rau nws cov immunogenicity.18
Kev sib txuas ntawm kev sib txuas feem ntau suav nrog kev sib txuas ntawm cov polymers los tsim cov ntawv cog lus, feem ntau suav nrog (-COOH) thiab / lossis hydroxyl (-OH) skeletons.Qee lub tebchaw tuaj yeem txhawb kev sib txuas, xws li 1,4-butanediol diglycidyl ether (BDDE) (Juvederm, Restylane, Princess), divinyl sulfone (Captique, Hylaform, Prevelle) lossis diepoxy octane (Puragen ).29 Txawm li cas los xij, pawg epoxy ntawm BDDE tau nruab nrab tom qab ua haujlwm nrog HA, yog li tsuas yog cov lej ntawm BDDE tsis muaj kev cuam tshuam (<2 feem ntawm ib lab) tuaj yeem pom hauv cov khoom.26 Hla-txuas ha hydrogel yog cov khoom siv tau zoo heev uas tuaj yeem ua rau tsim cov qauv 3D nrog cov khoom tshwj xeeb (rheology, degradation, applicability).Cov yam ntxwv no txhawb qhov kev faib tawm yooj yim ntawm cov khoom thiab tib lub sijhawm txhawb kev tsim cov khoom molecular ntawm extracellular matrix.30, 31<>
Txhawm rau ua kom cov hydrophilicity ntawm cov khoom, qee cov tuam ntxhab ntxiv lwm cov tshuaj, xws li dextran lossis mannitol.Txhua yam ntawm cov additives no yuav dhau los ua ib qho antigen uas txhawb kev tiv thaiv kab mob.
Tam sim no, HA npaj tau tsim los ntawm cov kab mob tshwj xeeb ntawm Streptococcus los ntawm cov kab mob fermentation.(Streptococcus equi lossis Streptococcus zooepidemicus).Piv nrog rau yav tas los siv cov tsiaj-los npaj, nws txo qhov kev pheej hmoo ntawm immunogenicity, tab sis nws tsis tuaj yeem tshem tawm cov kab mob ntawm cov protein molecules, cov kab mob nucleic acids thiab stabilizers.Lawv tuaj yeem dhau los ua cov tshuaj tiv thaiv thiab txhawb nqa tus tswv tsev lub cev tiv thaiv kab mob, xws li kev kub siab rau HA cov khoom.Yog li ntawd, cov cuab yeej siv tshuab muab tub lim (xws li Restylane) tsom rau kev txo cov khoom sib kis.32
Raws li lwm qhov kev xav, lub cev tiv thaiv kab mob rau HA yog tshwm sim los ntawm kev mob tshwm sim los ntawm cov kab mob biofilm, uas tau xa mus rau cov ntaub so ntswg thaum cov khoom txhaj tshuaj.33,34 Biofilm yog tsim los ntawm cov kab mob, lawv cov as-ham thiab metabolites.Nws feem ntau suav nrog cov kab mob tseem ceeb uas tsis yog kab mob uas ua rau cov tawv nqaij noj qab haus huv los yog cov mucous membranes (piv txwv li, Dermatobacterium acnes, Streptococcus oralis, Staphylococcus epidermidis).Cov kab mob no tau lees paub los ntawm cov tshuaj tiv thaiv kab mob polymerase.33-35 : kuv
Vim lawv qhov tshwj xeeb qeeb-loj hlob tus yam ntxwv thiab lawv cov kev hloov pauv hu ua me me colonies, feem ntau nyuaj rau txheeb xyuas cov kab mob hauv kab lis kev cai.Tsis tas li ntawd, lawv cov metabolism hauv biofilm yuav qeeb qeeb, uas yuav pab kom tsis txhob muaj cov tshuaj tua kab mob.35,36 Tsis tas li ntawd, lub peev xwm los tsim cov txheej txheem ntawm extracellular matrix ntawm extracellular polysaccharides (xws li HA) yog ib qho kev tiv thaiv rau phagocytosis.Cov kab mob no tuaj yeem nyob twj ywm rau ntau xyoo, tom qab ntawd raug qhib los ntawm lwm yam thiab ua rau muaj kev cuam tshuam.35-37 Macrophages thiab cov hlwb loj heev feem ntau pom muaj nyob rau thaj tsam ntawm cov kab mob no.Lawv tuaj yeem ua kom sai sai thiab ua rau muaj kev mob tshwm sim.38 Tej yam tseem ceeb, xws li kab mob kab mob nrog cov kab mob uas zoo sib xws hauv cov kab mob biofilms, tuaj yeem ua kom cov kab mob tsis muaj kab mob los ntawm kev siv tshuab mimicry.Kev ua kom tuaj yeem yog vim kev puas tsuaj los ntawm lwm cov txheej txheem dermal muab tub lim.38
Nws yog qhov nyuaj rau kev paub qhov txawv ntawm qhov mob thiab qeeb hypersensitivity los ntawm cov kab mob biofilms.Yog hais tias ib tug liab sclerotic lesion tshwm nyob rau txhua lub sij hawm tom qab phais, tsis hais lub sij hawm ntawm lub sij hawm, lub biofilm yuav tsum tau xav tias tam sim ntawd.38 Tej zaum nws yuav yog asymmetrical thiab symmetrical, thiab tej zaum nws yuav cuam tshuam rau txhua qhov chaw uas HA raug tswj xyuas thaum phais.Txawm hais tias kab lis kev cai tshwm sim tsis zoo, yuav tsum siv cov tshuaj tua kab mob dav dav nrog kev nkag mus rau hauv daim tawv nqaij.Yog hais tias muaj fibrous nodules nrog nce kuj, nws yuav yog ib tug txawv teb chaws lub cev granuloma.
HA kuj tseem tuaj yeem txhawb kev mob los ntawm cov txheej txheem ntawm superantigens.Cov lus teb no tsis xav tau cov theem pib ntawm o.12,39 Superantigens ua rau 40% ntawm thawj T hlwb thiab tej zaum NKT clonal activation.Kev ua kom cov lymphocytes no ua rau muaj cua daj cua dub cytokine, uas yog tus cwj pwm los ntawm kev tso tawm ntau ntawm pro-inflammatory cytokines, xws li IL-1β, IL-2, IL-6 thiab TNF-α40.
Kev mob ntsws hnyav, feem ntau nrog rau kev ua pa tsis ua haujlwm hnyav, yog ib qho piv txwv ntawm cov lus teb rau cov kab mob superantigen (staphylococcal enterotoxin B), uas ua rau LMW-HA ua los ntawm fibroblasts hauv cov ntaub so ntswg.HA txhawb kev tsim cov IL-8 thiab IP-10 chemokines, uas ua lub luag haujlwm tseem ceeb hauv kev nrhiav cov hlwb rau lub ntsws.40,41 Cov txheej txheem zoo sib xws tau pom nyob rau hauv chav kawm ntawm mob hawb pob, kab mob ntsws ntev thiab mob ntsws.Kev tsim tawm ntau ntxiv ntawm COVID-19.41 LMW-HA ua rau overstimulation ntawm CD44 thiab tso tawm cov pro-inflammatory cytokines thiab chemokines.40 Cov txheej txheem no tseem tuaj yeem pom nyob rau hauv qhov mob tshwm sim los ntawm cov khoom siv biofilm.
Thaum lub tshuab muab tub lim ntau lawm tsis yog qhov tseeb hauv xyoo 1999, qhov kev pheej hmoo ntawm cov tshuaj tiv thaiv qeeb tom qab HA txhaj tshuaj tau txiav txim siab yog 0.7%.Tom qab kev qhia txog cov khoom lag luam siab dawb huv, qhov xwm txheej ntawm cov xwm txheej tsis zoo no poob rau 0.02%.3,42,43 Txawm li cas los xij, kev qhia txog HA fillers uas sib txuas cov saw hlau siab thiab qis HA ua rau ntau dua AE feem pua.44
Thawj cov ntaub ntawv ntawm cov kev tshwm sim zoo li no tau tshwm sim hauv daim ntawv tshaj tawm txog kev siv NASHA.Qhov no yog ib qho erythema thiab edema cov tshuaj tiv thaiv, nrog infiltration thiab edema nyob rau hauv ib ncig ntawm lub cheeb tsam mus txog 15 hnub.Cov tshuaj tiv thaiv no tau pom hauv 1 ntawm 1400 tus neeg mob.3 Lwm tus kws sau ntawv tau tshaj tawm cov kab mob inflammatory nodules ntev, tshwm sim hauv 0.8% ntawm cov neeg mob.45 Lawv tau hais txog qhov etiology ntsig txog cov kab mob sib kis los ntawm cov kab mob fermentation.Raws li cov ntaub ntawv, qhov zaus ntawm kev phiv tshuaj yog 0.15-0.42%.3, 6, 43 ib
Nyob rau hauv rooj plaub ntawm kev siv lub sij hawm tus qauv, muaj ntau yam kev sim los faib cov kev tsis zoo ntawm HA.46
Bitterman-Deutsch et al.cais cov ua rau muaj kev phiv tshuaj thiab teeb meem tom qab phais nrog hyaluronic acid-raws li kev npaj.Lawv suav nrog
Cov pab pawg kws tshaj lij tau sim txhais cov lus teb rau hyaluronic acid raws li lub sijhawm tshwm sim tom qab phais: "thaum ntxov" (<14 hnub), "lig" (> 14 hnub rau 1 xyoo) lossis "ntev" (> 1 xyoo).47-49 Lwm cov kws sau ntawv tau faib cov lus teb ua ntej (mus txog ib lub lis piam), nruab nrab (ntev: ib lub lis piam mus rau ib hlis), thiab lig (ntau tshaj ib hlis).50 Tam sim no, cov lus teb qeeb thiab qeeb yog suav tias yog ib qho chaw, hu ua qeeb inflammatory teb (DIR), vim tias lawv cov laj thawj feem ntau tsis meej meej thiab kev kho mob tsis cuam tshuam txog qhov ua rau.42 Kev faib tawm ntawm cov kev cuam tshuam no tuaj yeem raug npaj raws li cov ntaub ntawv (Daim duab 3).
Transient edema ntawm qhov chaw txhaj tshuaj tam sim ntawd tom qab kev phais yuav yog vim qhov kev tso tawm ntawm cov tshuaj histamine hauv cov neeg mob uas muaj kev fab tshuaj rau hom 1, tshwj xeeb tshaj yog cov neeg muaj keeb kwm ntawm cov kab mob ntawm daim tawv nqaij.51 Nws tsuas yog ob peb feeb tom qab kev tswj hwm uas cov hlwb mast tau raug kev puas tsuaj thiab tso tawm cov tshuaj tiv thaiv kab mob ua rau cov ntaub so ntswg edema thiab cua loj tsim.Yog hais tias ib qho lus teb nrog mast hlwb tshwm sim, ib chav kawm ntawm kev kho antihistamine feem ntau yog txaus.51
Qhov loj dua ntawm daim tawv nqaij puas los ntawm kev phais kom zoo nkauj, qhov ntau dua qhov edema, uas tej zaum yuav nce mus txog 10-50%.52 Raws li randomized ob-dig muag multicenter cov neeg mob phau ntawv teev npe, qhov zaus ntawm edema tom qab txhaj tshuaj Restylane yog kwv yees li 87% ntawm txoj kev tshawb no 52,53
Cov chaw ntawm lub ntsej muag uas zoo li tshwj xeeb tshaj yog ua rau edema yog daim di ncauj, periorbital thiab sab plhu.52 Yuav kom txo tau qhov kev pheej hmoo, nws raug nquahu kom tsis txhob siv cov khoom ntim ntau, cov tshuaj loog infiltration, active massage thiab hygroscopic heev.Additives (mannitol, dextran).52
Edema ntawm qhov chaw txhaj tshuaj ntev li ob peb feeb mus rau 2-3 hnub tuaj yeem tshwm sim los ntawm hygroscopicity ntawm HA.Cov tshuaj tiv thaiv no feem ntau pom nyob rau hauv perilip thiab periorbital cheeb tsam.49,54 yuav tsum tsis txhob yuam kev rau edema tshwm sim los ntawm ib tug tsis tshua muaj mechanism ntawm kev tsis haum tshuaj tam sim ntawd (angioedema).49
Tom qab txhaj tshuaj Restylane (NASHA) nyob rau hauv daim di ncauj sab sauv, ib rooj plaub ntawm hypersensitivity rau angioedema tau piav qhia.Txawm li cas los xij, tus neeg mob kuj tau noj 2% lidocaine, uas tuaj yeem ua rau hom I hypersensitivity tshwm sim.Kev tswj hwm kev tswj hwm ntawm corticosteroids ua rau cov edema txo qis hauv 4 hnub.32
Qhov kev hloov pauv sai sai tuaj yeem yog vim qhov tsis txaus ntseeg rau cov protein seem ntawm cov kab mob HA synthesizing kab mob.Kev sib cuam tshuam ntawm kev txhaj tshuaj HA thiab cov seem mast hlwb hauv cov ntaub so ntswg yog lwm txoj hauv kev los qhia meej qhov tshwm sim tam sim ntawd.CD44 receptor nyob rau saum npoo ntawm mast hlwb yog cov receptor rau HA, thiab qhov kev cuam tshuam no yuav yog qhov tseem ceeb rau lawv txoj kev tsiv teb tsaws chaw.32,55 ib
Kev kho mob suav nrog kev tswj hwm tam sim ntawm cov tshuaj tiv thaiv kab mob, GCS, lossis epinephrine.46
Thawj tsab ntawv tshaj tawm, luam tawm los ntawm Turkmani li al., tau piav qhia txog cov poj niam hnub nyoog 22-65 uas tau txais kev phais HA uas tsim los ntawm cov tuam txhab sib txawv.39 Cov kab mob ntawm daim tawv nqaij yog tshwm sim los ntawm erythema thiab mob edema ntawm qhov chaw txhaj tshuaj ntawm lub ntsej muag.Nyob rau hauv txhua rooj plaub, cov lus teb pib 3-5 hnub tom qab mob khaub thuas (ua npaws, mob taub hau, mob caj pas, hnoos, thiab qaug zog).Tsis tas li ntawd, txhua tus neeg mob tau txais HA kev tswj hwm (2 txog 6 zaug) hauv 4 xyoos ua ntej cov tsos mob tshwm sim ntawm ntau qhov chaw ntawm lub ntsej muag.39
Kev nthuav qhia kho mob ntawm cov tshuaj tiv thaiv tau piav qhia (erythema thiab edema lossis urticaria zoo li pob liab liab nrog cov kab mob tshwm sim) zoo ib yam li hom III cov tshuaj tiv thaiv-pseudoserum mob.Hmoov tsis zoo, tsis muaj cov ntawv ceeb toom hauv cov ntaub ntawv uas lees paub qhov kev xav no.Ib daim ntawv tshaj tawm piav qhia txog tus neeg mob uas muaj pob khaus zoo li qhov txhab thaum lub sijhawm Sweet Syndrome, uas yog ib qho kab mob uas tshwm sim 24-48 teev tom qab HA qhov chaw tswj hwm.56
Qee tus kws sau ntawv ntseeg tias cov txheej txheem ntawm cov tshuaj tiv thaiv yog vim hom IV hypersensitivity.Kev txhaj tshuaj HA yav dhau los txhawb kev tsim cov qog ntshav qog ntshav, thiab kev tswj hwm tom qab ntawm qhov kev npaj sai sai ua rau cov lus teb ntawm CD4 + hlwb thiab macrophages.39
Tus neeg mob tau txais qhov ncauj prednisolone 20-30 mg lossis methylprednisolone 16-24 mg ib hnub rau 5 hnub.Tom qab ntawd qhov koob tshuaj tau txo rau lwm 5 hnub.Tom qab 2 lub lis piam, cov tsos mob ntawm 10 tus neeg mob uas tau txais qhov ncauj steroids ploj tag.Plaub tus neeg mob uas tseem tshuav tseem muaj mob me me.Hyaluronidase yog siv rau ib lub hlis tom qab pib cov tsos mob.39
Raws li cov ntaub ntawv, ntau qhov teeb meem qeeb yuav tshwm sim tom qab txhaj tshuaj hyaluronic acid.Txawm li cas los xij, txhua tus kws sau ntawv tau faib lawv raws li kev paub txog kev kho mob.Ib lub sij hawm sib koom ua ke lossis kev faib tawm tsis tau tsim los piav txog cov kev tsis zoo no.Lub sij hawm tsis tu ncua ncua ncua o (PIDS) tau txhais los ntawm Brazilian dermatologists hauv 2017. 57 Beleznay li al.tau qhia lwm lo lus los piav txog cov kab mob no hauv xyoo 2015: ncua kev pib nodule 15,58 thiab Snozzi li al.: advanced inflammatory response syndrome (LI).58 Hauv xyoo 2020, lwm lub sijhawm tau thov: ncua kev mob tshwm sim (DIR).48
Chung et al.hais ntxiv tias DIR suav nrog plaub hom kev tshwm sim: 1) DTH cov tshuaj tiv thaiv (hu ua kom raug: ncua hom IV cov tshuaj tiv thaiv tsis haum siab);2) txawv teb chaws lub cev granuloma tshuaj tiv thaiv;3) biofilm;4) kab mob atypical.DTH cov tshuaj tiv thaiv yog ib qho kev ncua ntawm lub cev tiv thaiv kab mob, uas yog cov lus teb rau kev ua xua.59
Raws li cov peev txheej sib txawv, nws tuaj yeem hais tau tias qhov zaus ntawm cov tshuaj tiv thaiv no sib txawv.Tsis ntev los no tau luam tawm ib daim ntawv sau los ntawm cov kws tshawb fawb Israeli.Lawv tau soj ntsuam tus naj npawb ntawm cov xwm txheej tsis zoo hauv daim ntawv DIR raws li daim ntawv nug.Daim ntawv nug tau ua tiav los ntawm 334 tus kws kho mob uas tau txhaj tshuaj HA.Cov txiaj ntsig tau pom tias yuav luag ib nrab ntawm cov tib neeg tsis tau kuaj pom tias muaj DIR, thiab 11.4% tau teb tias lawv tau soj ntsuam cov tshuaj tiv thaiv no ntau dua 5 zaug.48 Hauv kev xeem rau npe los ntsuas kev nyab xeeb, cov tshuaj tiv thaiv tshwm sim los ntawm cov khoom tsim los ntawm Allergan tau raug sau tseg zoo.Tom qab noj Juvederm Voluma® rau 24 lub hlis, kwv yees li 1% ntawm 103 tus neeg mob tau saib xyuas cov xwm txheej zoo sib xws.60 Thaum lub sij hawm 68-hli rov qab saib xyuas ntawm 4702 cov txheej txheem, cov qauv teb zoo sib xws tau pom hauv 0.5% ntawm cov neeg mob.Juvederm Voluma® tau siv hauv 2342 tus neeg mob.15 Qhov feem pua ​​​​siab dua tau pom thaum cov khoom siv Juvederm Volbella® tau siv rau hauv cov kua muag thiab daim di ncauj.Tom qab qhov nruab nrab ntawm 8 lub lis piam, 4.25% (n = 17) tau rov ua dua uas tau siv ntev txog 11 lub hlis (nruab nrab 3.17 ntu).42 Qhov kev ntsuam xyuas zaum kawg ntawm ntau tshaj li ib txhiab tus neeg mob uas tau txais kev kho mob Vycross rau 2-xyoo kev soj ntsuam nrog cov fillers pom tau hais tias qhov tshwm sim ntawm ncua nodules yog 1%.57 Chung thiab al. cov lus teb zaus rau daim ntawv tshaj tawm yog qhov tseem ceeb heev.Raws li kev suav ntawm cov kev tshawb fawb yav tom ntej, qhov tshwm sim ntawm cov lus teb qeeb qeeb yog 1.1% hauv ib xyoos, thaum nyob rau hauv kev tshawb fawb rov qab, nws tsawg dua 1% thaum lub sijhawm 1 txog 5.5 xyoo.Tsis yog txhua qhov xwm txheej tau tshaj tawm yog DIR tiag tiag vim tias tsis muaj qhov txhais tau meej.59
Kev ncua sij hawm inflammatory teb (DIR) thib ob rau kev tswj cov ntaub so ntswg ua rau tshwm sim tsawg kawg 2-4 lub lis piam lossis tom qab txhaj tshuaj HA.42 Cov kev kho mob tshwm sim yog nyob rau hauv daim ntawv ntawm rov tshwm sim ntawm lub zos edema, nrog rau erythema thiab rhiab, los yog subcutaneous nodules ntawm lub HA txhaj tshuaj.42,48 Cov nodules yuav sov rau qhov kov, thiab cov tawv nqaij ib puag ncig tej zaum yuav liab doog los yog xim av.Cov neeg mob feem ntau muaj kev cuam tshuam hauv txhua qhov chaw tib lub sijhawm.Nyob rau hauv rooj plaub uas tau siv HA ua ntej, tsis hais hom muab tub lim lossis cov koob txhaj tshuaj, nws yog ib qho tseem ceeb uas qhia txog qhov tshwm sim ntawm kev kho mob.15,39 Cov kab mob ntawm daim tawv nqaij muaj ntau dua nyob rau hauv cov neeg uas yav tas los txhaj koob tshuaj HA ntau.43 Tsis tas li ntawd, qhov edema nrog rau qhov pom tseeb tshaj plaws tom qab sawv, thiab nws zoo dua me ntsis thoob plaws ib hnub.42,44,57 Qee cov neeg mob (~ 40%) muaj cov kab mob sib kis zoo li mob khaub thuas.15
Cov tshuaj tiv thaiv no yuav cuam tshuam nrog kev sib kis ntawm DNA, protein, thiab kab mob endotoxin, txawm tias qhov concentration qis dua li ntawm HA.15 Txawm li cas los xij, LMW-HA kuj tseem tuaj yeem muaj nyob rau hauv cov tib neeg uas muaj kab mob genetic susceptible ncaj qha los yog los ntawm cov kab mob sib kis (biofilms).15,44 Txawm li cas los xij, qhov tshwm sim ntawm cov kab mob inflammatory nodules ntawm ib qho kev ncua deb ntawm qhov chaw txhaj tshuaj, qhov kev tiv thaiv ntawm tus kab mob mus rau kev siv tshuaj tua kab mob mus sij hawm ntev thiab tsis suav nrog cov kab mob sib kis (kev coj noj coj ua thiab kuaj PCR)) ua rau muaj kev tsis txaus siab txog lub luag haujlwm ntawm biofilms. .Tsis tas li ntawd, qhov ua tau zoo ntawm kev kho mob hyaluronidase thiab kev vam khom ntawm HA koob tshuaj qhia txog cov txheej txheem ntawm kev ncua sijhawm hypersensitivity.42,44 ib
Cov lus teb vim yog kis kab mob lossis raug mob tuaj yeem ua rau muaj kev nce ntxiv hauv cov tshuaj interferon, uas tuaj yeem ua rau mob ua ntej ua ntej.15,57,61 Tsis tas li ntawd, LMW-HA txhawb nqa CD44 lossis TLR4 receptors nyob rau saum npoo ntawm macrophages thiab dendritic hlwb.Nws qhib lawv thiab xa cov cim costimulatory rau T hlwb.15,19,24 Inflammatory nodules txuam nrog DIR tshwm sim nyob rau hauv 3 mus rau 5 lub hlis tom qab txhaj tshuaj HMW-HA muab tub lim (nrog rau cov tshuaj tiv thaiv kab mob), uas ces decompose thiab hloov mus rau hauv LMW- nrog pro-inflammatory zog HA.15
Qhov pib ntawm cov tshuaj tiv thaiv feem ntau tshwm sim los ntawm lwm cov txheej txheem kab mob (sinusitis, urinary kab mob, kab mob ua pa, kab mob hniav), raug mob ntawm lub ntsej muag, thiab kev phais hniav.57 Cov tshuaj tiv thaiv no kuj tshwm sim los ntawm kev txhaj tshuaj tiv thaiv thiab rov tshwm sim vim los ntshav los ntshav.15, 57 Txhua ntu tej zaum yuav tshwm sim los ntawm kev kis kab mob.
Qee tus kws sau ntawv kuj tau piav qhia txog cov noob caj noob ces ntawm cov tib neeg uas muaj cov subtypes hauv qab no los teb: HLA B * 08 lossis DRB1 * 03.4 (plaub-fold nce hauv kev pheej hmoo).13,62 ib
Cov kab mob ntsig txog DIR yog tus cwj pwm los ntawm inflammatory nodules.Lawv yuav tsum paub qhov txawv ntawm nodules, abscesses (softening, fluctuations), thiab granulomatous tshua (nyuaj inflammatory nodules) tshwm sim los ntawm biofilms.58
Chung et al.thov kom siv HA cov khoom siv rau kev kuaj tawv nqaij ua ntej cov txheej txheem npaj, txawm hais tias lub sijhawm xav tau los txhais cov txiaj ntsig kev xeem yuav yog 3-4 lub lis piam.59 Lawv qhia tshwj xeeb rau cov kev sim no rau cov neeg uas muaj xwm txheej phem.Kuv twb pom ua ntej lawm.Yog tias qhov kev kuaj pom tau zoo, tus neeg mob yuav tsum tsis txhob rov kho dua nrog tib HA muab tub lim.Txawm li cas los xij, nws yuav tsis tshem tawm tag nrho cov tshuaj tiv thaiv vim tias lawv feem ntau tshwm sim los ntawm qhov tshwm sim, xws li kab mob sib kis uas tuaj yeem tshwm sim txhua lub sijhawm.59