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Ukusabela kwezidakamizwa nge-eosinophilia kanye nezimpawu zesistimu (DRESS), eyaziwa nangokuthi i-hypersensitivity syndrome ebangelwa izidakamizwa, ukusabela okubi kwe-T-cell-mediated cutaneous okubonakala ngokuqubuka, ukushisa, ukubandakanyeka kwezitho zangaphakathi, nezimpawu zesistimu ngemva kokusetshenziswa isikhathi eside kwezidakamizwa ezithile.
UKUDUKA kwenzeka cishe ku-1 ku-1,000 kuya ko-1 ezigulini ezingu-10,000 ezithola imithi, kuye ngokuthi hlobo luni lomuthi ohehayo. Iningi lezimo ze-DRESS zidalwe izidakamizwa ezinhlanu, ngokwehla kwezehlakalo: i-allopurinol, i-vancomycin, i-lamotrigine, i-carbamazepine, ne-trimethopridine-sulfamethoxazole. Nakuba i-DRESS ingavamile uma kuqhathaniswa, ihlanganisa kuze kufike ku-23% wokusabela kwezidakamizwa zesikhumba ezigulini ezilaliswe esibhedlela.Izimpawu ze-Prodromal ze-DRESS (impendulo yezidakamizwa ezine-eosinophilia kanye nezimpawu zesistimu) zihlanganisa umkhuhlane, ukugula okuvamile, umphimbo obuhlungu, ubunzima bokugwinya, ukulunywa, ukushiswa kwesikhumba, noma inhlanganisela yalokhu okungenhla. Ngemva kwalesi sigaba, iziguli zivame ukuba nokuqhuma okufana nesimungumungwane eqala ku-torso nasebusweni bese isakazeka kancane kancane, ekugcineni ivale ngaphezu kwamaphesenti angu-50 esikhumba emzimbeni. I-edema ebusweni ingenye yezici eziphawulekayo ze-DRESS futhi ingase ikhulise noma iholele ekwakhiweni kwendlebe entsha etshekile, esiza ekuhlukaniseni i-DRESS nokuqubuka kwezidakamizwa okungeyona inkimbinkimbi okufana nesimungumungwane.

Iziguli ezine-DRESS zingase zibe nezilonda ezihlukahlukene, okuhlanganisa i-urticaria, eczema, izinguquko ze-lichenoid, i-exfoliative dermatitis, i-erythema, izilonda ezimise okuhlosiwe, i-purpura, ama-blister, ama-pustules, noma inhlanganisela yalokhu. Izilonda zesikhumba eziningi zingase zibe khona esigulini esisodwa ngesikhathi esisodwa noma zishintshe njengoba isifo siqhubeka. Ezigulini ezinesikhumba esimnyama, i-erythema yokuqala ingase ingabonakali, ngakho-ke idinga ukuhlolwa ngokucophelela ngaphansi kwezimo ezinhle zokukhanya. Ama-pustules avamile ebusweni, entanyeni nasesifubeni.

Ocwaningweni olulindelekile, oluqinisekisiwe, oluqinisekisiwe lweRegistry YaseYurophu Yokusabela Okubi Okubi Kakhulu (RegiSCAR), ama-56% eziguli ze-DRESS athuthuke ukuvuvukala kolwelwesi lwamafinyila kanye nokuguguleka, kanti u-15% weziguli ezinokuvuvukala kwe-mucosal okubandakanya amasayithi amaningi, ngokuvamile i-oropharynx. kwandulela izimpawu zesikhumba. Ukuqubuka kuvame ukuthatha isikhathi esingaphezu kwamasonto amabili futhi kunesikhathi eside sokululama, lapho i-superficial desquamation iyisici esiyinhloko. Ukwengeza, nakuba kuyivelakancane kakhulu, kunenani elincane leziguli ezine-DRESS okungenzeka zingahambisane nokuqubuka noma i-eosinophilia.

Izilonda zesistimu ze-DRESS ngokuvamile zihlanganisa igazi, isibindi, izinso, amaphaphu, nezinhlelo zenhliziyo, kodwa cishe zonke izitho zezitho (kuhlanganise ne-endocrine, i-gastrointestinal, neurological, ocular, kanye nesistimu ye-rheumatic) zingabandakanyeka. Ocwaningweni lwe-RegiSCAR, amaphesenti angama-36 eziguli okungenani abe nesitho esisodwa esingaphandle kwesikhumba esihilelekile, kanti amaphesenti angama-56 anezitho ezimbili noma ngaphezulu ezihilelekile. I-Atypical lymphocytosis iwukungajwayelekile kwe-hematological okuvamile futhi kwasekuqaleni, kuyilapho i-eosinophilia ivamise ukwenzeka ezigabeni zakamuva zesifo futhi ingase iqhubeke.
Ngemuva kwesikhumba, isibindi siyisitho esiqinile esithinteka kakhulu. Amazinga aphakeme e-enzyme esibindi angase enzeka ngaphambi kokuba kuvele ukuqubuka, ngokuvamile ngokwezinga eliphansi, kodwa ngezinye izikhathi kungase kufinyelele izikhathi ezifika kweziyi-10 kunomkhawulo ongaphezulu kovamile. Uhlobo oluvame kakhulu lokulimala kwesibindi yi-cholestasis, okulandelwa yi-cholestasis exubile kanye nokulimala kwe-hepatocellular. Ezimweni ezingavamile, ukwehluleka kwesibindi okunamandla kungase kube nzima ngokwanele ukuze kudinge ukufakelwa kwesibindi. Ezimeni ze-DRESS ezinokungasebenzi kahle kwesibindi, isigaba sezidakamizwa esivame kakhulu ama-antibiotics. Ukubuyekezwa okuhlelekile kuhlaziye iziguli ze-71 (abadala abangu-67 kanye nezingane ezingu-4) ezine-renal sequelae ehlobene ne-DRES. Nakuba iziguli eziningi zinokulimala kwesibindi ngesikhathi esisodwa, isiguli esisodwa kwezi-5 sitholakala ngokubandakanyeka kwezinso ezizimele kuphela. Imithi elwa namagciwane kwakuyizidakamizwa ezivame kakhulu ezihlobene nokulimala kwezinso ezigulini ze-DRESS, ne-vancomycin ebangela amaphesenti angu-13 okulimala kwezinso, kulandelwa i-allopurinol nama-anticonvulsants. Ukulimala okukhulu kwezinso kwakuphawulwa ukwanda kwezinga le-serum creatinine noma ukwehla kwezinga lokuhlunga kwe-glomerular, kanti ezinye izimo zazihambisana ne-proteinuria, i-oliguria, i-hematuria noma zonke ezintathu. Ngaphezu kwalokho, kungase kube ne-hematuria noma i-proteinuria ehlukanisiwe kuphela, noma kungabikho ngisho nomchamo. Ama-30% eziguli ezithintekile (21/71) athole ukwelashwa okushintshwa kwezinso, kanti ngenkathi iziguli eziningi ziphinde zasebenza ezinso, bekungacaci ukuthi zikhona yini ezinye zesikhathi eside ezilandelanayo. Ukubandakanyeka kwamaphaphu, okubonakala ngokuphelelwa umoya, ukukhwehlela okomile, noma kokubili, kubikwe ku-32% weziguli ze-DRESS. Izinkinga ezivame kakhulu zamaphaphu ekuhlolweni kwe-imaging zihlanganisa ukungena kwangaphakathi, i-acute Respiratory Distress Syndrome kanye ne-pleural effusion. Izinkinga zihlanganisa inyumoniya ye-interstitial acute, inyumoniya ye-lymphocytic interstitial, kanye ne-pleurisy. Njengoba i-DRESS yamaphaphu ivame ukubonwa ngokungeyikho njenge-pneumonia, ukuxilongwa kudinga ukuqapha okuphezulu. Cishe zonke izimo zokubandakanyeka kwamaphaphu zihambisana nokunye ukungasebenzi kahle kwesitho esiqinile. Kokunye ukubuyekezwa okuhlelekile, kufika ku-21% weziguli ze-DRESS zine-myocarditis. I-myocarditis ingase ibambezeleke izinyanga eziningi ngemva kokudamba kwezinye izimpawu ze-DRESS, noma ziqhubeka. Izinhlobo zisukela ku-acute eosinophilic myocarditis (ukukhululwa ngokwelashwa kwe-immunosuppressive yesikhashana) kuya ku-acute necrotizing eosinophilic myocarditis (ukufa okungaphezu kuka-50% kanye nokusinda okumaphakathi kwezinsuku ezi-3 kuya kwezi-4 kuphela). Iziguli ezine-myocarditis zivame ukuba ne-dyspnea, ubuhlungu besifuba, i-tachycardia, ne-hypotension, ehambisana namazinga aphezulu e-enzyme ye-myocardial, izinguquko ze-electrocardiogram, kanye nokungahambi kahle kwe-echocardiographic (njengokuphuma kwe-pericardial, ukungasebenzi kahle kwe-systolic, i-ventricular septal hypertrophy, nokwehluleka kwe-biventricular). I-cardiac magnetic resonance imaging ingaveza izilonda ze-endometrial, kodwa ukuxilongwa okuqondile ngokuvamile kudinga i-endometrial biopsy. Ukubandakanyeka kwamaphaphu ne-myocardial akuvamile kakhulu ku-DRESS, futhi i-minocycline ingenye ye-ejenti evame kakhulu yokugqugquzela.

Uhlelo lwamaphuzu lwe-European RegiSCAR luqinisekisiwe futhi lusetshenziswa kabanzi ekuxilongweni kwe-DRESS (Ithebula 2). Uhlelo lokushaya amaphuzu lusekelwe ezicini eziyisikhombisa: izinga lokushisa eliyisisekelo lomzimba ngaphezu kuka-38.5 ° C; Ama-lymph nodes akhulisiwe okungenani ezindaweni ezimbili; I-Eosinophilia; I-lymphocytosis ye-atypical; Ukuqubuka (okumboza ngaphezu kwamaphesenti angama-50 obuso bomzimba, ukubonakaliswa kokuma kwesici, noma okutholwe nge-histological okuhambisana nokuzwela ngokweqile kwezidakamizwa); Ukubandakanyeka kwezitho ezingaphandle kwesikhumba; Futhi ukuxolelwa isikhathi eside (ngaphezu kwezinsuku eziyi-15).
Amaphuzu asukela ku-−4 kuya ku-9, futhi isiqiniseko sokuxilonga singahlukaniswa sibe amazinga amane: amaphuzu angaphansi kuka-2 abonisa ukuthi asikho isifo, u-2 kuya ku-3 ubonisa ukuthi kungenzeka isifo, u-4 kuya ku-5 ubonisa ukuthi kungenzeka ukuthi unesifo, futhi ngaphezu kuka-5 ubonisa ukuxilongwa kwe-DRESS. Isikolo se-RegiSCAR siwusizo ngokukhethekile ekuqinisekiseni okusemuva kwamacala angenzeka ngenxa yokuthi iziguli kungenzeka azihlangabezananga ngokugcwele nazo zonke izindlela zokuxilonga ekuqaleni kwesifo noma azizange zikuthole ukuhlola okuphelele okuhlobene namaphuzu.

I-DRESS idinga ukuhlukaniswa kwezinye izimo ezimbi kakhulu zesikhumba, okuhlanganisa i-SJS neziyaluyalu ezihlobene, i-toxic epidermal necrolysis (TEN), kanye ne-acute generalized exfoliating impetigo (AGEP) (Figure 1B). Isikhathi sokufukamela se-DRESS sivamise ukuba side kunezinye izifo ezimbi kakhulu zesikhumba. I-SJS ne-TEN zikhula ngokushesha futhi ngokuvamile zizixazulula ngokwazo phakathi kwamaviki angu-3 kuya kwangu-4, kuyilapho izimpawu ze-DRESS zivame ukuphikelela. Nakuba ukubandakanyeka kwe-mucosal ezigulini ze-DRESS kungase kudingeke ukuba kuhlukaniswe ku-SJS noma i-TEN, izilonda zomlomo womlomo ku-DRESS ngokuvamile ukopha okuncane futhi kuncane. Isici esimakiwe sokuvuvukala kwesikhumba se-DRESS singase siholele kumabhamuza esibili e-caatonic kanye nokuguguleka, kuyilapho i-SJS ne-TEN zibonakala ngokucwecwa kwesikhumba esigcwele ungqimba olunokuqina kwezinhlangothi, ngokuvamile okubonisa uphawu luka-Nikolsky oluhle. Ngokuphambene, i-AGEP ivamise ukuvela emahoreni kuya ezinsukwini ngemva kokuchayeka emuthini futhi ixazululeka ngokushesha phakathi kwamaviki angu-1 kuya kwangu-2. Ukuqubuka kwe-AGEP kugobile futhi kwakhiwe ama-pustules ajwayelekile angavaleli ezinhlamvini zezinwele, ahluke kancane ezicini ze-DRESS.
Ucwaningo olungase lube khona lubonise ukuthi u-6.8% weziguli ze-DRESS zazinezici zakho zombili i-SJS, TEN noma i-AGEP, lapho u-2.5% wazo wawubhekwa njengokugqagqene okunemiphumela emibi kakhulu yesikhumba. Ukusetshenziswa kwenqubo yokuqinisekisa ye-RegiSCAR kusiza ukuhlonza lezi zimo ngokunembile.
Ukwengeza, ukuqubuka kwezidakamizwa okujwayelekile okufana nesimungumungwane kuvame ukuvela emasontweni angu-1 kuya kwangu-2 ngemva kokuchayeka emuthini (ukuvezwa kabusha kuyashesha), kodwa ngokungafani ne-DRESS, lokhu kuqubuka ngokuvamile akuvamisile ukuhambisana nokuphakama kwe-transaminase, ukwanda kwe-eosinophilia, noma isikhathi eside sokululama kusukela ezimpawu. INGUBO nayo idinga ukuhlukaniswa kwezinye izindawo zesifo, okuhlanganisa i-hemophagocytic lymphohistiocytosis, i-vascular immunoblastic T-cell lymphoma, nesifo esibi kakhulu se-graft-versus-host.

Ukuvumelana kochwepheshe noma iziqondiso mayelana nokwelashwa kwe-DRESS akuzange kwenziwe; Izincomo zokwelashwa ezikhona zisekelwe kudatha yokuqaphela kanye nombono wochwepheshe. Izifundo zokuqhathanisa zokuqondisa ukwelashwa nazo azikho, ngakho izindlela zokwelapha azifani.
Sula ukwelashwa kwezidakamizwa ezibanga izifo
Isinyathelo sokuqala nesibaluleke kakhulu ku-DRESS ukuhlonza nokuyeka umuthi okungenzeka ube yimbangela. Ukwakha amashadi emithi anemininingwane yeziguli kungasiza kule nqubo. Ngokuhlelwa kwezidakamizwa, odokotela bangakwazi ukubhala ngokuhlelekile yonke imithi ebanga izifo futhi bahlaziye ubudlelwano besikhashana phakathi kokuchayeka kwezidakamizwa nokuqubuka, i-eosinophilia, nokubandakanyeka kwezitho. Besebenzisa lolu lwazi, odokotela bangahlola umuthi okungenzeka ukuthi uqalise i-DRESS futhi bayeke ukusebenzisa lowo muthi kusenesikhathi. Ngaphezu kwalokho, odokotela bangaphinde babhekisele kuma-algorithms asetshenziselwa ukunquma imbangela yezidakamizwa kwezinye izimo ezimbi kakhulu zesikhumba.

Umuthi - glucocorticoids
I-Systemic glucocorticoids iyindlela eyinhloko yokunxenxa ukukhululwa kwe-DRESS nokwelapha ukuphindeka. Nakuba umthamo wokuqala ovamile ungu-0.5 kuya ku-1 mg/d/kg ngosuku (ukalwa ngokulingana ne-prednisone), kukhona ukuntuleka kokuhlolwa komtholampilo okuhlola ukusebenza kahle kwe-corticosteroids ye-DRESS, kanye nocwaningo lwemithamo ehlukene nezinhlobo zokwelashwa. Umthamo we-glucocorticoids akufanele wehliswe ngokungafanele kuze kube yilapho kubonakala ukuthuthuka okucacile komtholampilo, njengokunciphisa ukuqubuka, i-eosinophil penia, nokubuyiselwa kokusebenza kwesitho. Ukuze unciphise ingozi yokuphindaphinda, kunconywa ukunciphisa kancane kancane umthamo we-glucocorticoids ngaphezu kwamaviki angu-6 kuya kwangu-12. Uma umthamo ojwayelekile ungasebenzi, khona-ke ukwelashwa kwe-glucocorticoid "kwe-shack", 250 mg nsuku zonke (noma okulinganayo) izinsuku ezingu-3, ​​kungase kucatshangelwe, kulandelwe ukunciphisa kancane kancane.
Ezigulini ezine-DRESS emnene, i-topical corticosteroids esebenza kahle kakhulu ingaba inketho yokwelapha esebenzayo. Isibonelo, u-Uhara et al. kubika ukuthi iziguli ezingu-10 DRESS zilulame ngempumelelo ngaphandle kwe-systemic glucocorticoids. Kodwa-ke, ngenxa yokuthi akucaci ukuthi yiziphi iziguli ezingagwema ngokuphepha ukwelashwa okuhleliwe, ukusetshenziswa okubanzi kwemithi yokwelapha ye-topical akunconywa njengenye indlela.

Gwema ukwelashwa kwe-glucocorticoid kanye nokwelashwa okuhlosiwe
Ezigulini ze-DRESS, ikakhulukazi lezo ezisengozini enkulu yezinkinga (ezifana nezifo) ezivela ekusetshenzisweni kwemithamo ephezulu ye-corticosteroids, izindlela zokwelapha zokugwema i-corticosteroid zingacatshangelwa. Nakuba kube nemibiko yokuthi i-intravenous immunoglobulin (IVIG) ingase isebenze kwezinye izimo, ucwaningo oluvulekile lubonise ukuthi ukwelapha kunengozi enkulu yemiphumela emibi, ikakhulukazi i-thromboembolism, okuholela ezigulini eziningi ekugcineni zishintshele ekwelashweni kwe-systemic glucocorticoid. Ukusebenza okungaba khona kwe-IVIG kungase kuhlotshaniswe nomphumela wayo wokususa amasosha omzimba, okusiza ukuvimbela ukutheleleka ngegciwane noma ukuvuselela igciwane. Kodwa-ke, ngenxa yemithamo emikhulu ye-IVIG, ingase ingafaneleki ezigulini ezinokuhluleka kwenhliziyo eqinile, ukwehluleka kwezinso, noma ukwehluleka kwesibindi.
Ezinye izindlela zokwelapha zihlanganisa i-mycophenolate, i-cyclosporin ne-cyclophosphamide. Ngokuvimbela ukusebenza kwe-T cell, i-cyclosporine ivimba ukulotshwa kofuzo kwama-cytokines afana ne-interleukin-5, ngaleyo ndlela kuncishiswe ukuqashwa kwe-eosinophilic kanye nokusebenza kwe-T cell eqondene nezidakamizwa. Ucwaningo oluhilela iziguli ezinhlanu eziphathwe nge-cyclosporine kanye neziguli ezingu-21 eziphathwe nge-systemic glucocorticoids lubonise ukuthi ukusetshenziswa kwe-cyclosporine kwakuhlotshaniswa namazinga aphansi okuqhubeka kwesifo, izinyathelo ezithuthukisiwe zomtholampilo nezaselabhorethri, kanye nokuhlala okufushane esibhedlela. Nokho, i-cyclosporine okwamanje ayithathwa njengokwelashwa komugqa wokuqala kwe-DRESS. I-Azathioprine ne-mycophenolate zisetshenziselwa kakhulu ukwelashwa kokulungisa esikhundleni sokwelashwa kokungeniswa.
Amasosha omzimba e-Monoclonal asetshenziselwe ukwelapha i-DRESS. Lokhu kufaka phakathi i-Mepolizumab, i-Ralizumab, ne-benazumab evimba i-interleukin-5 kanye ne-axis yokwamukela, i-Janus kinase inhibitors (njenge-tofacitinib), kanye nama-anti-CD20 monoclonal antibodies (afana ne-rituximab). Phakathi kwalezi zindlela zokwelapha, izidakamizwa ze-anti-interleukin-5 zibhekwa njengendlela yokwelapha yokungeniswa okufinyelelekayo, ephumelelayo futhi ephephile. Indlela yokusebenza kahle ingase ihlotshaniswe nokuphakama kwangaphambi kwesikhathi kwamazinga e-interleukin-5 ku-DRESS, ngokuvamile ebangelwa amaseli e-T aqondene nomuthi othile. I-Interleukin-5 ingumlawuli oyinhloko wama-eosinophils futhi unesibopho sokukhula kwawo, ukuhlukaniswa, ukuqashwa, ukuqhutshwa kanye nokuphila. Izidakamizwa ze-anti-interleukin-5 zivame ukusetshenziselwa ukwelapha iziguli ezisene-eosinophilia noma ukungasebenzi kahle kwesitho ngemva kokusetshenziswa kwe-systemic glucocorticoids.

Ubude besikhathi sokwelashwa
Ukwelashwa kwe-DRESS kudinga ukwenziwa kube ngokwakho kakhulu futhi kulungiswe ngendlela eguquguqukayo ngokuya ngokuqhubeka kwesifo kanye nokusabela kokwelashwa. Iziguli ezine-DRESS ngokuvamile zidinga ukulaliswa esibhedlela, futhi cishe ingxenye yesine yalezi zimo zidinga ukuphathwa kokunakekelwa okuphuthumayo. Ngesikhathi sokulaliswa esibhedlela, izimpawu zesiguli zihlolwa nsuku zonke, ukuhlolwa okuphelele komzimba kwenziwa, futhi izinkomba zaselabhorethri zibhekwa njalo ukuze zihlole ukubandakanyeka kwezitho kanye nezinguquko kuma-eosinophil.
Ngemuva kokukhishwa, ukuhlolwa kokulandelela kwamasonto onke kusadingeka ukuze kuqashwe izinguquko esimweni futhi kulungiswe uhlelo lokwelapha ngesikhathi. Ukuphindeka kabusha kungase kwenzeke ngokuzenzakalelayo ngesikhathi sokuncipha komthamo we-glucocorticoid noma ngemva kokukhululwa, futhi kungase kuvele njengophawu olulodwa noma isilonda sesitho sendawo, ngakho iziguli zidinga ukugadwa isikhathi eside nangokuphelele.