nkhani

Kuyankha kwa mankhwala ndi eosinophilia ndi zizindikiro za systemic (DRESS), yomwe imadziwikanso kuti mankhwala-induced hypersensitivity syndrome, ndi vuto lalikulu la T-cell-mediated cutaneous reaction lomwe limadziwika ndi zotupa, kutentha thupi, kukhudzidwa kwa ziwalo zamkati, ndi zizindikiro zowonongeka pambuyo pogwiritsira ntchito mankhwala ena kwa nthawi yaitali.
KUVALA kumachitika pafupifupi 1 mwa 1,000 mpaka 1 mwa odwala 10,000 omwe amalandira mankhwala, kutengera mtundu wa mankhwala opangitsa. Nthawi zambiri za DRESS zinayambitsidwa ndi mankhwala asanu, motsika kwambiri: allopurinol, vancomycin, lamotrigine, carbamazepine, ndi trimethopridine-sulfamethoxazole. Ngakhale kuti DRESS ndi yosowa kwambiri, imakhala ndi 23% ya zochitika za mankhwala a khungu kwa odwala omwe ali m'chipatala.Zizindikiro za Prodromal za DRESS (mankhwala osokoneza bongo ndi eosinophilia ndi zizindikiro za systemic) zimaphatikizapo kutentha thupi, kupweteka kwapang'onopang'ono, kupweteka kwapakhosi, kumeza movutikira, kuyabwa, kutentha kwa khungu, kapena kuphatikiza zomwe zili pamwambazi. Pambuyo pa siteji iyi, odwala nthawi zambiri amakhala ndi zidzolo ngati chikuku zomwe zimayambira pamphuno ndi kumaso ndikufalikira pang'onopang'ono, ndipo pamapeto pake zimaphimba 50% ya khungu pathupi. Kutupa kumaso ndi chimodzi mwazinthu zodziwika bwino za DRESS ndipo zimatha kukulitsa kapena kupangitsa kuti khutu la khutu liwoneke, lomwe limathandiza kusiyanitsa DRESS ndi chiwopsezo chamankhwala chosavuta ngati chikuku.

Odwala omwe ali ndi DRESS amatha kukhala ndi zilonda zosiyanasiyana, kuphatikizapo urticaria, eczema, kusintha kwa lichenoid, exfoliative dermatitis, erythema, zilonda zooneka ngati chandamale, purpura, matuza, pustules, kapena kuphatikiza kwa izi. Zilonda zambiri zapakhungu zingakhalepo mwa wodwala yemweyo panthawi imodzi kapena kusintha pamene matendawa akupita. Odwala omwe ali ndi khungu lakuda, erythema yoyambirira sangawonekere, chifukwa chake iyenera kuyang'aniridwa mosamala pakuwunikira bwino. Ma pustules amapezeka pankhope, khosi ndi pachifuwa.

Mu kafukufuku wovomerezeka, wovomerezeka wa European Registry of Serious Cutaneous Adverse Reactions (RegiSCAR), 56% ya odwala DRESS anayamba kutupa ndi kukokoloka kwa mucosal pang'ono, ndi 15% ya odwala omwe ali ndi kutupa kwa mucosal komwe kumaphatikizapo malo angapo, makamaka oropharynx. amatsogolera zizindikiro za khungu. Zidzolo nthawi zambiri zimatha milungu yopitilira iwiri ndipo zimakhala ndi nthawi yayitali yochira, pomwe desquamation yachiphamaso ndiye chinthu chachikulu. Kuonjezera apo, ngakhale kuti ndizosowa kwambiri, pali odwala ochepa omwe ali ndi DRESS omwe sangatsatire ndi zotupa kapena eosinophilia.

Kuwonongeka kwadongosolo kwa DRESS nthawi zambiri kumaphatikizapo magazi, chiwindi, impso, mapapo, ndi machitidwe a mtima, koma pafupifupi machitidwe onse a ziwalo (kuphatikizapo endocrine, m'mimba, mitsempha, ocular, ndi rheumatic systems) akhoza kuphatikizidwa. Mu kafukufuku wa RegiSCAR, 36 peresenti ya odwala anali ndi chiwalo chimodzi chowonjezera chokhudzidwa, ndipo 56 peresenti anali ndi ziwalo ziwiri kapena kuposerapo. Atypical lymphocytosis ndiye vuto lodziwika bwino komanso loyambirira kwambiri la hematological, pomwe eosinophilia nthawi zambiri imapezeka kumapeto kwa matendawa ndipo imatha kupitilirabe.
Pambuyo pa khungu, chiwindi ndi chiwalo cholimba chomwe chimakhudzidwa kwambiri. Kuchuluka kwa michere ya chiwindi kumatha kuchitika zidzolo zisanachitike, nthawi zambiri mpaka pang'ono, koma nthawi zina zimatha kufika kuchulukitsa ka 10 kuposa momwe zimakhalira. Mtundu wofala kwambiri wa kuvulala kwa chiwindi ndi cholestasis, chotsatiridwa ndi cholestasis chosakanikirana ndi kuvulala kwa hepatocellular. Nthawi zina, kulephera kwachiwindi kumatha kukhala kokulirapo mpaka kufuna kuyika chiwindi. Pankhani ya DRESS yokhala ndi vuto la chiwindi, gulu lodziwika bwino la mankhwala opha tizilombo ndi maantibayotiki. Kuwunika mwadongosolo kunasanthula odwala 71 (akuluakulu 67 ndi ana a 4) omwe ali ndi DRES-renal sequelae. Ngakhale kuti odwala ambiri amawononga chiwindi nthawi imodzi, 1 mwa odwala 5 amakhala ndi vuto la impso lokhalokha. Maantibayotiki anali mankhwala odziwika kwambiri okhudzana ndi kuwonongeka kwa impso kwa odwala DRESS, ndi vancomycin kuchititsa 13 peresenti ya kuwonongeka kwa impso, kutsatiridwa ndi allopurinol ndi anticonvulsants. Kuvulala kwakukulu kwa aimpso kumadziwika ndi kuchuluka kwa serum creatinine kapena kuchepa kwa kusefera kwa glomerular, ndipo nthawi zina kumatsagana ndi proteinuria, oliguria, hematuria kapena onse atatu. Kuphatikiza apo, pangakhale hematuria yokhayokha kapena proteinuria, kapena palibe mkodzo. 30% ya odwala omwe adakhudzidwa (21/71) adalandira chithandizo chobwezeretsa aimpso, ndipo ngakhale odwala ambiri adayambiranso kugwira ntchito kwa impso, sizikudziwika ngati panali zotsatira zanthawi yayitali. Kutengapo gawo m'mapapo, komwe kumadziwika ndi kupuma movutikira, chifuwa chowuma, kapena zonse ziwiri, zidanenedwa mu 32% ya odwala DRESS. Zovuta zodziwika bwino zama pulmonary pakuwunika koyerekeza ndi kulowetsedwa kwapakati, kupuma movutikira, komanso pleural effusion. Zovuta zake zimaphatikizapo chibayo chapakati chapakati, chibayo cha lymphocytic interstitial, ndi pleurisy. Popeza kuti DRESS ya m'mapapo imazindikiridwa molakwika ngati chibayo, kutulukira kumafuna kusamala kwambiri. Pafupifupi milandu yonse yokhudzana ndi mapapu imatsagana ndi vuto lina lolimba la chiwalo. Pakuwunika kwina mwadongosolo, mpaka 21% ya odwala DRESS anali ndi myocarditis. Myocarditis ikhoza kuchedwa kwa miyezi zizindikiro zina za DRESS zitatha, kapena kupitilirabe. Mitunduyi imayambira pachimake eosinophilic myocarditis (kukhululukidwa ndi chithandizo chanthawi yayitali cha immunosuppressive) mpaka pachimake necrotizing eosinophilic myocarditis (imfa yopitilira 50% ndi kupulumuka kwapakati kwa masiku atatu mpaka 4 okha). Odwala omwe ali ndi myocarditis nthawi zambiri amakhala ndi dyspnea, kupweteka pachifuwa, tachycardia, ndi hypotension, limodzi ndi kuchuluka kwa michere ya myocardial, kusintha kwa electrocardiogram, ndi zovuta za echocardiographic (monga pericardial effusion, systolic dysfunction, ventricular septal hypertrophy, ndi biventricular failure). Kujambula kwa maginito a mtima kukhoza kuwulula zilonda zam'mimba, koma kufufuza kotsimikizika nthawi zambiri kumafuna endometrial biopsy. Kukhudzidwa kwa m'mapapo ndi myocardial sikofala kwambiri mu DRESS, ndipo minocycline ndi imodzi mwazinthu zochititsa chidwi kwambiri.

European RegiSCAR scoring system yatsimikiziridwa ndipo imagwiritsidwa ntchito kwambiri pozindikira za DRESS (Table 2). Dongosolo la zigoli limachokera ku makhalidwe asanu ndi awiri: kutentha kwapakati pa thupi pamwamba pa 38.5 ° C; Kukulitsa ma lymph nodes m'malo osachepera awiri; Eosinophilia; Atypical lymphocytosis; Ziphuphu (zophimba 50% ya thupi lonse, mawonekedwe a morphological, kapena zotsatira za histological zogwirizana ndi hypersensitivity ya mankhwala); Kuphatikizidwa kwa ziwalo zakunja; Ndipo kukhululukidwa kwanthawi yayitali (masiku opitilira 15).
Zolembazo zimachokera ku -4 mpaka 9, ndipo kutsimikizika kwa matenda kungagawidwe m'magulu anayi: mapepala omwe ali pansipa 2 amasonyeza kuti palibe matenda, 2 mpaka 3 amasonyeza matenda omwe angakhalepo, 4 mpaka 5 amasonyeza kuti ali ndi matenda aakulu, ndipo oposa 5 amasonyeza matenda a DRESS. Chiwerengero cha RegiSCAR ndi chothandiza kwambiri pakutsimikiziranso zam'mbuyo zomwe zingatheke chifukwa odwala sangakhale atakwaniritsa njira zonse zodziwira matenda kumayambiriro kwa matendawa kapena sanalandire kuwunika kokwanira kokhudzana ndi mphambu.

KUVALA kuyenera kusiyanitsidwa ndi zovuta zina zapakhungu, kuphatikiza SJS ndi zovuta zina, poizoni epidermal necrolysis (TEN), ndi acute generalized exfoliating impetigo (AGEP) (Chithunzi 1B). Nthawi ya makulitsidwe a DRESS nthawi zambiri imakhala yayitali kusiyana ndi zovuta zina zapakhungu. SJS ndi TEN zimakula mwachangu ndipo nthawi zambiri zimakhazikika paokha mkati mwa 3 mpaka masabata a 4, pomwe zizindikiro za DRESS zimakhala zokhazikika. Ngakhale kuti kukhudzidwa kwa mucosal kwa odwala DRESS kungafunikire kusiyanitsidwa ndi SJS kapena TEN, zotupa za m'kamwa mu DRESS nthawi zambiri zimakhala zochepa komanso zochepa. Chizindikiro cha edema pakhungu la DRESS chingayambitse matuza achiwiri a catatonic ndi kukokoloka, pomwe SJS ndi TEN amadziwika ndi kutulutsa kwathunthu kwa epidermal exfoliation ndi lateral tension, nthawi zambiri kuwonetsa chizindikiro cha Nikolsky. Mosiyana ndi zimenezi, AGEP nthawi zambiri imawoneka maola kwa masiku pambuyo pokhudzana ndi mankhwalawa ndipo imathetsa mofulumira mkati mwa 1 mpaka masabata a 2. Kuthamanga kwa AGEP kumakhala kokhotakhota ndipo kumapangidwa ndi ma pustules amtundu uliwonse omwe samangokhalira kutsitsi, omwe ndi osiyana pang'ono ndi makhalidwe a DRESS.
Kafukufuku woyembekezeredwa adawonetsa kuti 6.8% ya odwala DRESS anali ndi mawonekedwe a SJS, TEN kapena AGEP, pomwe 2.5% amawonedwa kuti anali ndi zovuta zowopsa zapakhungu. Kugwiritsa ntchito njira zovomerezeka za RegiSCAR kumathandizira kuzindikira izi.
Kuonjezera apo, ziwengo zomwe zimagwiritsidwa ntchito ngati chikuku nthawi zambiri zimawonekera mkati mwa 1 kwa masabata a 2 mutatha kugwiritsa ntchito mankhwalawa (kuwonetsetsanso mofulumira), koma mosiyana ndi DRESS, zotupazi sizimatsagana ndi transaminase okwera, kuwonjezeka kwa eosinophilia, kapena kuchira kwa nthawi yaitali kuchokera ku zizindikiro. KUVALA kumafunikanso kulekanitsidwa ndi madera ena a matenda, kuphatikizapo hemophagocytic lymphohistiocytosis, vascular immunoblastic T-cell lymphoma, ndi acute graft-versus-host disease.

Chigwirizano cha akatswiri kapena malangizo okhudza chithandizo cha DRESS sichinapangidwe; Malangizo omwe alipo kale amathandizidwa ndi zomwe akuwona komanso malingaliro a akatswiri. Maphunziro ofananiza otsogolera chithandizo akusowanso, kotero njira zachipatala sizili zofanana.
Kuchiza bwino mankhwala oyambitsa matenda
Gawo loyamba komanso lofunika kwambiri mu DRESS ndikuzindikira ndikusiya mankhwala omwe angayambitse. Kupanga ma chart atsatanetsatane amankhwala kwa odwala kungathandize ndi izi. Pogwiritsa ntchito mankhwala osokoneza bongo, asing'anga amatha kulemba mwadongosolo mankhwala onse omwe angayambitse matenda ndikuwunika ubale wanthawi yayitali pakati pa kukhudzidwa kwa mankhwala ndi zidzolo, eosinophilia, ndi kukhudzidwa kwa chiwalo. Pogwiritsa ntchito chidziwitsochi, madokotala amatha kuyang'ana mankhwala omwe angayambitse DRESS ndikusiya kugwiritsa ntchito mankhwalawa panthawi yake. Kuphatikiza apo, asing'anga amathanso kunena za ma aligorivimu omwe amagwiritsidwa ntchito kuti adziwe chomwe chimayambitsa mankhwala pazovuta zina zazikulu zapakhungu.

mankhwala - glucocorticoids
Systemic glucocorticoids ndiye njira yayikulu yochepetsera chikhululukiro cha DRESS ndikuchiza kubwereza. Ngakhale kuti mlingo woyambira wamba ndi 0.5 mpaka 1 mg/d/kg pa tsiku (kuyezedwa mu prednisone ofanana), pali kusowa kwa mayesero a zachipatala omwe amayesa mphamvu ya corticosteroids kwa DRESS, komanso maphunziro a mitundu yosiyanasiyana ya mankhwala ndi mankhwala. Mlingo wa glucocorticoids sayenera kuchepetsedwa mosasamala mpaka kusintha kowoneka bwino kwachipatala, monga kuchepetsa zidzolo, eosinophil mbolo, ndi kubwezeretsanso kwa chiwalo. Kuti muchepetse chiopsezo chobwereza, tikulimbikitsidwa kuchepetsa pang'onopang'ono mlingo wa glucocorticoids pazaka 6 mpaka 12. Ngati mlingo wokhazikika sukugwira ntchito, ndiye kuti mankhwala a glucocorticoid "ogwedezeka", 250 mg tsiku lililonse (kapena ofanana) kwa masiku atatu, akhoza kuganiziridwa, ndikutsatiridwa ndi kuchepetsa pang'onopang'ono.
Kwa odwala omwe ali ndi DRESS yofatsa, ma topical corticosteroids ogwira mtima kwambiri atha kukhala njira yabwino yochizira. Mwachitsanzo, Uhara et al. adanenanso kuti odwala 10 DRESS adachira bwino popanda systemic glucocorticoids. Komabe, chifukwa sizidziwikiratu kuti ndi odwala ati omwe angapewe kuchiritsa kwadongosolo, kugwiritsa ntchito kwambiri mankhwala apakhungu sikuvomerezedwa ngati njira ina.

Pewani chithandizo cha glucocorticoid ndi chithandizo chomwe mukufuna
Kwa odwala DRESS, makamaka omwe ali pachiwopsezo chachikulu cha zovuta (monga matenda) chifukwa chogwiritsa ntchito mlingo waukulu wa corticosteroids, njira zopewera za corticosteroid zingaganizidwe. Ngakhale kuti pakhala pali malipoti oti intravenous immunoglobulin (IVIG) ikhoza kukhala yothandiza nthawi zina, kafukufuku wotseguka wasonyeza kuti mankhwalawa ali ndi chiopsezo chachikulu cha zotsatirapo zoipa, makamaka thromboembolism, zomwe zimachititsa odwala ambiri kuti apite ku systemic glucocorticoid therapy. Kuthekera kwa IVIG kumatha kukhala kogwirizana ndi kuthekera kwake kwa antibody clearance, komwe kumathandiza kuletsa matenda a virus kapena kuyambitsanso kachilomboka. Komabe, chifukwa cha kuchuluka kwa IVIG, sikungakhale koyenera kwa odwala omwe ali ndi vuto la mtima, kulephera kwa impso, kapena kulephera kwa chiwindi.
Njira zina zothandizira ndi mycophenolate, cyclosporin ndi cyclophosphamide. Mwa kuletsa T cell activation, cyclosporine imatchinga kulembedwa kwa jini kwa ma cytokines monga interleukin-5, potero amachepetsa kulembedwa kwa eosinophilic komanso kuyambitsa ma cell a T cell. Kafukufuku wokhudza odwala asanu omwe amathandizidwa ndi cyclosporine ndi odwala 21 omwe amathandizidwa ndi systemic glucocorticoids adawonetsa kuti kugwiritsa ntchito cyclosporine kumalumikizidwa ndi kutsika kwa matenda, kupititsa patsogolo njira zamankhwala ndi ma laboratory, komanso nthawi yayitali m'chipatala. Komabe, cyclosporine pakali pano sichikuganiziridwa ngati chithandizo choyamba cha DRESS. Azathioprine ndi mycophenolate amagwiritsidwa ntchito makamaka pokonza chithandizo m'malo mwa chithandizo chodzidzimutsa.
Ma antibodies a monoclonal akhala akugwiritsidwa ntchito pochiza DRESS. Izi zikuphatikiza Mepolizumab, Ralizumab, ndi benazumab zomwe zimatsekereza interleukin-5 ndi receptor axis, Janus kinase inhibitors (monga tofacitinib), ndi anti-CD20 monoclonal antibodies (monga rituximab). Pakati pazithandizozi, mankhwala oletsa anti-interleukin-5 amaonedwa kuti ndi omwe amapezeka kwambiri, ogwira ntchito komanso otetezeka. Njira yogwirira ntchitoyo ingakhale yokhudzana ndi kukwera koyambirira kwa ma interleukin-5 mu DRESS, yomwe nthawi zambiri imayambitsidwa ndi maselo a T omwe ali ndi mankhwala. Interleukin-5 ndiye woyang'anira wamkulu wa eosinophils ndipo ali ndi udindo pakukula kwawo, kusiyanitsa, kulembera anthu ntchito, kuyambitsa ndi kupulumuka. Mankhwala oletsa anti-interleukin-5 amagwiritsidwa ntchito pochiza odwala omwe adakali ndi eosinophilia kapena kuwonongeka kwa chiwalo atagwiritsa ntchito systemic glucocorticoids.

Kutalika kwa mankhwala
Kuchiza kwa DRESS kumafunika kukhala kwamunthu payekha komanso kusinthidwa mwamphamvu malinga ndi momwe matenda akupitira patsogolo komanso kuyankha kwamankhwala. Odwala omwe ali ndi DRESS nthawi zambiri amafunikira kugonekedwa m'chipatala, ndipo pafupifupi gawo limodzi mwa magawo anayi aliwonse amtunduwu amafunikira chisamaliro chambiri. Panthawi yogonekedwa m'chipatala, zizindikiro za wodwalayo zimayesedwa tsiku ndi tsiku, kufufuza kwakukulu kwa thupi kumachitidwa, ndipo zizindikiro za labotale zimayang'aniridwa nthawi zonse kuti ziwone kukhudzidwa kwa ziwalo ndi kusintha kwa eosinophils.
Pambuyo pa kutulutsidwa, kuyezetsa kotsatira kwa mlungu ndi mlungu kumafunikabe kuti ayang'ane kusintha kwa chikhalidwecho ndikusintha ndondomeko ya chithandizo panthawi yake. Kubwereranso kumatha kuchitika mwadzidzidzi panthawi ya kuchepa kwa mlingo wa glucocorticoid kapena pambuyo pa kukhululukidwa, ndipo kungakhale chizindikiro chimodzi kapena zotupa za m'deralo, kotero odwala ayenera kuyang'aniridwa nthawi yaitali komanso momveka bwino.