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Mhinduro yezvinodhaka ine eosinophilia uye systemic zviratidzo (DRESS), inozivikanwawo sezvinodhaka-induced hypersensitivity syndrome, inotyisa T-cell-mediated cutaneous adverse reaction inoratidzwa nekuputika, fivha, kubatanidzwa kwenhengo dzomukati, uye zviratidzo zvehurongwa mushure mekushandisa kwenguva refu mamwe madhiragi.
KUSVIRWA kunoitika mune angangoita 1 mu1,000 kusvika 1 mu10,000 varwere vanowana mushonga, zvichienderana nerudzi rwemushonga wekuita. Zvizhinji zvezviitiko zveDRESS zvakakonzerwa nemishonga mishanu, mukudzika kwechiitiko: allopurinol, vancomycin, lamotrigine, carbamazepine, uye trimethopridine-sulfamethoxazole. Kunyange zvazvo DRESS isingawanzoitiki, inosvika ku23% yemishonga yeganda muvarwere vari muchipatara.Prodromal zviratidzo zveDRESS (mhinduro yezvinodhaka ne eosinophilia uye zviratidzo zve systemic) zvinosanganisira fever, general malaise, kurwadziwa kwehuro, kunetseka kumedza, kuputika, kupisa kweganda, kana kusanganiswa kwezviri pamusoro apa. Mushure meiyi nhanho, varwere vanowanzoita mapundu akafanana negwirikwiti anotangira padumbu nekumeso uye zvishoma nezvishoma anopararira, pakupedzisira achivhara zvinopfuura 50% yeganda pamuviri. Facial edema ndechimwe chezvimiro zveDRESS uye inogona kuwedzera kana kutungamirira kune itsva oblique ear lobe crease, iyo inobatsira kusiyanisa DRESS kubva kune isina kuoma gwirikwiti-kufanana nemushonga.

Varwere vane DRESS vanogona kupa nemhando dzakasiyana-siyana, kusanganisira urticaria, eczema, lichenoid shanduko, exfoliative dermatitis, erythema, maronda-akafanana nechinangwa, purpura, blisters, pustules, kana kusanganiswa kweizvi. Zvipembenene zvakawanda zveganda zvinogona kunge zviripo mumurwere mumwe chete panguva imwe chete kana kuchinja sezvo chirwere chinokura. Mune varwere vane ganda rakasviba, erythema yekutanga inogona kunge isingaonekwe, saka inoda kuongororwa zvakanyatsonaka pasi pemamiriro emwenje. Pustules inowanzoitika pachiso, mutsipa uye nzvimbo yechipfuva.

Muchidzidzo cheEuropean Registry of Serious Cutaneous Adverse Reactions (RegiSCAR) chidzidzo, 56% yevarwere veDRESS vakagadzira zvinyoro mucosal kuzvimba uye kukukurwa, ne15% yevarwere vane mucosal kuzvimba kunosanganisira nzvimbo dzakawanda, kazhinji iyo oropharynx. inotangira zviratidzo zveganda. Iyo rash inowanzotora mavhiki anopfuura maviri uye ine nguva yakareba yekupora, apo superficial desquamation ndiyo inonyanya kukosha. Mukuwedzera, kunyange zvazvo zvisingawanzoitiki, kune nhamba shomanana yevarwere vane DRESS vangave vasina kuperekedzwa nepundu kana eosinophilia.

Systemic maronda eDRESS anowanzobatanidza ropa, chiropa, itsvo, mapapu, uye masystems emwoyo, asi anenge ese enhengo system (kusanganisira endocrine, gastrointestinal, neurological, ocular, uye rheumatic system) inogona kubatanidzwa. Muchidzidzo cheRegiSCAR, zvikamu makumi matatu nenhanhatu kubva muzana zvevarwere vaive nenhengo imwe chete yekunze yakachekeka, uye 56 muzana vaive nenhengo mbiri kana kupfuura dzaibatanidzwa. Atypical lymphocytosis ndiyo yakajairika uye yekutanga hematological abnormality, nepo eosinophilia inowanzoitika mumatanho ekupedzisira echirwere uye inogona kuramba ichienderera.
Mushure meganda, chiropa ndicho chinonyanya kukanganiswa nhengo yakasimba. Kukwidziridzwa kwe enzyme yechiropa kunogona kuitika kusati kwaonekwa mapundu, kazhinji kusvika pamwero wakapfava, asi dzimwe nguva anogona kusvika kusvika kagumi pane epamusoro muganhu wezvakajairwa. Rudzi rwakawanda rwekukuvara kwechiropa ndeye cholestasis, inoteverwa necholestasis yakasanganiswa uye kukuvara kwehepatocellular. Muzviitiko zvisingawanzoitiki, kutadza kwechiropa kwakanyanya kunogona kunge kwakakomba zvekuti zvinoda kuisirwa chiropa. Muzviitiko zveDRESS nekusashanda zvakanaka kwechiropa, kirasi inonyanyozivikanwa yemishonga inorwisa mabhakitiriya. Ongororo yakarongeka yakaongorora varwere ve71 (67 vakuru nevana 4) vane DRES-yakabatana renal sequelae. Kunyangwe varwere vazhinji vaine kukuvara kwechiropa panguva imwe chete, 1 muvashanu varwere varipo nekungobatanidzwa kweitsvo dzega. Mishonga inorwisa mabhakitiriya ndiyo yainyanyozivikanwa yakabatana nekukuvara kweitsvo muvarwere veDRESS, ine vancomycin ichikonzera 13 muzana yekukuvara kweitsvo, ichiteverwa neallopurinol uye anticonvulsants. Kukuvara kwakanyanya renal kwakaratidzwa nekuwedzera serum creatinine level kana kuderera kweglomerular filtration rate, uye zvimwe zviitiko zvaiperekedzwa neproteinuria, oliguria, hematuria kana ese matatu. Mukuwedzera, panogona kuva nehematuria yakazvimiririra kana proteinuria, kana kunyange pasina weti. 30% yevarwere vakakanganisika (21/71) vakagamuchira renal replacement therapy, uye nepo varwere vazhinji vakawanazve itsvo basa, hazvina kujeka kana paine kwenguva yakareba sequelae. Kubatanidzwa kwemapapu, kunoratidzwa nekupfupika kwekufema, chikosoro chakaoma, kana zvose zviri zviviri, zvakashumwa mu32% yevarwere veDRESS. Izvo zvinowanzoitika pulmonary abnormalities pakuongororwa kwekufungidzira zvinosanganisira kupindira kwemukati, acute respiratory distress syndrome uye pleural effusion. Zvinetso zvinosanganisira acute interstitial pneumonia, lymphocytic interstitial pneumonia, uye pleurisy. Sezvo pulmonary DRESS ichiwanzoonekwa zvisiri izvo semabayo, kuongororwa kunoda mwero wepamusoro wekuchenjerera. Zvinenge zvese zviitiko zvine kubatanidzwa kwemapapu zvinoperekedzwa neimwe yakasimba nhengo kusagadzikana. Mune kumwe kuongorora kwakarongeka, kusvika ku21% yevarwere veDRESS vaiva nemyocarditis. Myocarditis inogona kunonoka kwemwedzi yakawanda mushure mokunge zvimwe zviratidzo zveDRESS zvapera, kana kuti kunyange kuramba. Mhando idzi dzinobva paacute eosinophilic myocarditis (remission with short-term immunosuppressive treatment) kusvika kune acute necrotizing eosinophilic myocarditis (kufa kwevanopfuura 50% uye kurarama kwepakati kwemazuva matatu kusvika mana chete). Varwere vane myocarditis vanowanzouya ne dyspnea, kurwadziwa kwechipfuva, tachycardia, uye hypotension, inoperekedzwa nepamusoro-soro yemyocardial enzyme, kuchinja kwe electrocardiogram, uye echocardiographic abnormalities (zvakadai se pericardial effusion, systolic dysfunction, ventricular septal hypertrophy, uye biventricular failure). Cardiac magnetic resonance imaging inogona kuratidza maronda eendometrial, asi kuongororwa kwechokwadi kunowanzoda endometrial biopsy. Kubatanidzwa kwemapapu uye myocardial hazvinyanyi kuwanika muDRESS, uye minocycline ndeimwe yeanonyanya kukonzera.

IEuropean RegiSCAR scoring system yakasimbiswa uye inoshandiswa zvakanyanya kuongororwa kweDRESS (Table 2). The scoring system inobva pane zvinomwe maitiro: kupisa kwepakati kwemuviri kunopfuura 38.5 ° C; Kuwedzera lymph nodes munzvimbo dzinenge mbiri; Eosinophilia; Atypical lymphocytosis; Rash (inofukidza inopfuura 50% yenzvimbo yemuviri, hunhu morphological kuratidzwa, kana histological kuwanikwa kunoenderana nemishonga hypersensitivity); Kubatanidzwa kwenhengo dze extra-cutaneous; Uye kuregererwa kwenguva refu (kupfuura mazuva gumi nemashanu).
Nhamba yezvikamu kubva -4 kusvika ku9, uye chokwadi chekuongorora chinogona kugoverwa muzvikamu zvina: chikamu chiri pasi pe2 chinoratidza kuti hapana chirwere, 2 kusvika ku3 inoratidza chirwere chinogona kuitika, 4 kusvika ku5 inoratidza chirwere chinogona kuitika, uye kupfuura 5 inoratidza kuongororwa kweDRESS. Mucherechedzo weRegiSCAR unonyanya kubatsira pakudzokorora kusimbiswa kwezviitiko zvinogona kuitika nokuti varwere vangave vasina kukwana zvakakwana maitiro ose ekuongorora chirwere pakutanga kwechirwere kana kuti vasina kugamuchira kuongororwa kwakakwana kwakabatana nechikwata.

KUSVIRWA kunoda kusiyaniswa kubva kune mamwe maitiro akakomba eganda, anosanganisira SJS nezvimwe zvine hukama, toxic epidermal necrolysis (TEN), uye acute generalized exfoliating impetigo (AGEP) (Mufananidzo 1B). Nguva yeincubation yeDRESS inowanzorebesa pane mamwe maitiro akakomba eganda. SJS neTEN vanokura nekukurumidza uye vanowanzogadzirisa vari voga mukati memavhiki matatu kusvika mana, nepo DRESS zviratidzo zvichiramba zvichiramba. Kunyange zvazvo mucosal kubatanidzwa muDRESS varwere vangada kusiyaniswa kubva kuSJS kana TEN, oral mucosal maronda muDRESS anowanzova akapfava uye asina kubuda ropa. Mucherechedzo weganda edema maitiro eDRESS anogona kutungamirira ku catatonic secondary blisters uye kukukurwa, nepo SJS neTEN zvinoratidzirwa ne-full-layer epidermal exfoliation ne lateral tension, kazhinji ichiratidza chiratidzo chaNikolsky chakanaka. Kusiyana neizvi, AGEP inowanzoonekwa maawa kusvika kumazuva mushure mekusangana nemishonga uye inogadzirisa nokukurumidza mukati me1 kusvika kumavhiki maviri. Iyo rash yeAGEP yakakombama uye inoumbwa neakawanda pustules asina kuvharirwa kune bvudzi follicles, iyo yakati siyanei nehunhu hweDRESS.
Imwe ongororo yakaitwa yakaratidza kuti 6.8% yevarwere veDRESS vaive nezvikamu zveSJS, TEN kana AGEP, iyo 2.5% yaionekwa seine kupindirana kwakanyanya kwakashata kweganda. Iko kushandiswa kweRegiSCAR yekusimbisa maitiro kunobatsira kunyatsoona aya mamiriro.
Mukuwedzera, gwirikwiti-kufanana nemishonga inodhaka inowanzoonekwa mukati me1 kusvika kumavhiki e2 mushure mekusangana nemushonga (kuratidzwazve kunokurumidza), asi kusiyana neDRESS, kuputika uku hakuwanzoperekedzwa nepamusoro-soro transaminase, kuwedzera eosinophilia, kana nguva yakareba yekudzorera kubva kune zviratidzo. NGUO inodawo kusiyaniswa nedzimwe nzvimbo dzechirwere, kusanganisira hemophagocytic lymphohistiocytosis, vascular immunoblastic T-cell lymphoma, uye acute graft-versus-host disease.

Kubvumirana kwenyanzvi kana mazano pamusoro pekurapa kweDRESS hazvina kugadzirwa; Kurudziro dzekurapa dziripo dzinobva pane yekutarisa data uye maonero enyanzvi. Kuenzanisa zvidzidzo zvekutungamira kurapwa zvakare kushomeka, saka nzira dzekurapa hadzina kufanana.
Kurapa kwezvinodhaka kunokonzera zvirwere
Danho rekutanga uye rakanyanya kukosha muDRESS nderekuziva nekumisa mushonga unonyanya kukonzera. Kugadzira machati emishonga akadzama evarwere anogona kubatsira nekuita uku. Nekudhirowa kwezvinodhaka, varapi vanogona kunyora zvakarongeka zvese zvinogona kukonzera chirwere zvinodhaka uye kuongorora hukama hwenguva pakati pekuratidzwa kwezvinodhaka uye rash, eosinophilia, uye kubatanidzwa kwenhengo. Vachishandisa ruzivo urwu, vanachiremba vanogona kuvheneka mushonga unonyanya kukonzera DRESS uye kurega kushandisa mushonga iwoyo nenguva. Uye zvakare, varapi vanogona zvakare kutaura kune algorithms anoshandiswa kuona zvinodhaka causation kune mamwe maitiro akakomba eganda.

Mushonga - glucocorticoids
Systemic glucocorticoids ndiyo nzira huru yekukurudzira kuregererwa kweDRESS uye kurapa kudzoka. Kunyange zvazvo muyero wepakutanga uri 0.5 kusvika 1 mg/d/kg pazuva (inoyerwa muprednisone yakaenzana), pane kushomeka kwemiedzo yekiriniki inoongorora kushanda kwecorticosteroids yeDRESS, pamwe nezvidzidzo pamiyero yakasiyana-siyana uye zvirongwa zvekurapa. Chiyero cheglucocorticoids hachifanirwe kuderedzwa zvisina tsarukano kudzamara kwakajeka kuvandudzwa kwekiriniki kwaonekwa, sekuderedza kuputika, eosinophil penia, uye kudzoreredzwa kwebasa renhengo. Kuti uderedze njodzi yekudzokazve, zvinokurudzirwa kuderedza zvishoma nezvishoma dose yeglucocorticoids pamusoro pe6 kusvika kumavhiki e12. Kana iyo chiyero cheyero isingashande, ipapo "kuvhundutsa" glucocorticoid therapy, 250 mg zuva nezuva (kana yakaenzana) kwemazuva matatu, inogona kutariswa, inoteverwa nekuderera zvishoma nezvishoma.
Kune varwere vane nyoro DRESS, inoshanda zvakanyanya topical corticosteroids inogona kunge iri nzira yekurapa inoshanda. Somuenzaniso, Uhara et al. yakashuma kuti 10 varwere DRESS vakapora zvinobudirira pasina systemic glucocorticoids. Nekudaro, nekuti hazvina kujeka kuti ndevapi varwere vanogona kudzivirira zvakachengeteka kurapwa kwehurongwa, kushandiswa kwakapararira kwekurapa kwepamusoro hakukurudzirwe seimwe nzira.

Dzivisa glucocorticoid therapy uye yakanangwa kurapa
Kune varwere veDRESS, kunyanya avo vari pangozi yakakura yezvinetso (zvakadai sezvirwere) kubva pakushandiswa kwepamusoro-soro ye corticosteroids, corticosteroid kudzivisa kurapa kunogona kufungwa. Kunyangwe paine mishumo yekuti intravenous immunoglobulin (IVIG) inogona kushanda mune dzimwe nguva, ongororo yakavhurika yakaratidza kuti kurapwa kwacho kune njodzi huru yemhedzisiro yakaipa, kunyanya thromboembolism, zvichiita kuti varwere vazhinji vazopedzisira vachinja kune systemic glucocorticoid therapy. Iko kugona kushanda kweIVIG kunogona kuve kwakabatana neiyo antibody clearance effect, iyo inobatsira kuvharidzira hutachiona hwehutachiona kana kudzoreredza hutachiona. Nekudaro, nekuda kweiyo yakakura madhizi eIVIG, inogona kunge isina kukodzera kune varwere vane congestive moyo kutadza, itsvo kutadza, kana chiropa kutadza.
Dzimwe nzira dzokurapa dzinosanganisira mycophenolate, cyclosporin uye cyclophosphamide. Nekudzivisa T cell activation, cyclosporine inovhara gene transcription ye cytokines yakadai se interleukin-5, nokudaro kuderedza eosinophilic recruitment uye zvinodhaka-specific T cell activation. Chidzidzo chinosanganisira varwere vashanu vanobatwa ne cyclosporine uye 21 varwere vakabatwa ne systemic glucocorticoids yakaratidza kuti kushandiswa kwe cyclosporine kwaibatanidza nemitengo yakaderera yekufambira mberi kwechirwere, kuvandudzwa kwekiriniki uye marabhoritari matanho, uye kupfupika kwechipatara kugara. Nekudaro, cyclosporine haisati yaonekwa semutsetse wekutanga kurapwa kweDRESS. Azathioprine uye mycophenolate inonyanya kushandiswa kugadzirisa kurapwa kwete induction therapy.
Masoja ekudzivirira chirwere anonzi monoclonal akashandiswa kurapa DRESS. Izvi zvinosanganisira Mepolizumab, Ralizumab, uye benazumab inovhara interleukin-5 uye receptor axis, Janus kinase inhibitors (senge tofacitinib), uye anti-CD20 monoclonal antibodies (serituximab). Pakati pemishonga iyi, anti-interleukin-5 mishonga inofungidzirwa kuti ndiyo inonyanya kuwanikwa, inoshanda uye yakachengeteka induction therapy. Iyo nzira yekubudirira inogona kunge yakabatana nekukwira kwekutanga kwe interleukin-5 mazinga muDRESS, iyo inowanzokonzerwa nemishonga-yakananga T masero. Interleukin-5 ndiyo inonyanya kutonga eosinophils uye inokonzera kukura kwavo, kusiyanisa, kuunganidza, kushandiswa uye kurarama. Anti-interleukin-5 zvinodhaka zvinowanzoshandiswa kurapa varwere vachiri eosinophilia kana nhengo yemuviri kusagadzikana mushure mekushandisa systemic glucocorticoids.

Nguva yekurapa
Kurapa kweDRESS kunoda kuve kwakanyanya munhu uye kugadziridzwa zvine simba zvinoenderana nekufambira mberi kwechirwere uye mhinduro yekurapa. Varwere vane DRESS vanowanzoda kurapwa, uye chikamu chimwe muzvina chezviitiko izvi zvinoda kutarisirwa kwakanyanya. Munguva yechipatara, zviratidzo zvemurwere zvinoongororwa zuva rega rega, kuongorora kwakakwana kwemuviri kunoitwa, uye zviratidzo zverabhoritari zvinogara zvichiongororwa kuti zviongorore kubatanidzwa kwenhengo uye kuchinja mune eosinophils.
Mushure mokusunungurwa, kuongororwa kwevhiki nevhiki kwekutsvaga kuchiri kudiwa kutarisa kuchinja kwemamiriro ezvinhu uye kugadzirisa chirongwa chekurapa munguva. Kudzokorora kunogona kuitika pakarepo panguva yeglucocorticoid dose inoderera kana mushure mekuregererwa, uye inogona kupa sechiratidzo chimwe chete kana chironda chemukati chemukati, saka varwere vanoda kuongororwa kwenguva refu uye zvakakwana.