labarai

Amsar miyagun ƙwayoyi tare da eosinophilia da bayyanar cututtuka na tsarin (DRESS), wanda kuma aka sani da ciwon hawan jini na miyagun ƙwayoyi, wani mummunan mummunan sakamako ne na T-cell wanda ke da alaƙa da kurji, zazzaɓi, shigar da gabobin ciki, da bayyanar cututtuka na tsarin bayan amfani da wasu kwayoyi na tsawon lokaci.
DRESS yana faruwa a kusan 1 cikin 1,000 zuwa 1 a cikin 10,000 marasa lafiya waɗanda ke karɓar magani, ya danganta da nau'in ƙwayar cuta. Yawancin shari'o'in DRESS sun samo asali ne ta hanyar magunguna biyar, a cikin tsari na saukowa: allopurinol, vancomycin, lamotrigine, carbamazepine, da trimethopridine-sulfamethoxazole. Kodayake DRESS yana da wuyar gaske, yana da lissafin har zuwa 23% na halayen maganin fata a cikin marasa lafiya na asibiti.Prodromal bayyanar cututtuka na DRESS (maganin magani tare da eosinophilia da alamun cututtuka) sun haɗa da zazzabi, rashin lafiya na gaba ɗaya, ciwon makogwaro, wahalar haɗiye, itching, kona fata, ko haɗuwa da na sama. Bayan wannan matakin, marasa lafiya sukan sami kurji mai kama da kyanda wanda ke farawa daga gaɓoɓi da fuska kuma a hankali ya bazu, a ƙarshe ya rufe fiye da kashi 50% na fata a jiki. edema na fuska yana ɗaya daga cikin sifofin DRESS kuma yana iya ƙara tsanantawa ko haifar da sabon kumburin kunnen da ba a taɓa gani ba, wanda ke taimakawa wajen rarrabe DRESS daga cutar kyanda mara rikitarwa kamar kurjin magani.

Marasa lafiya tare da DRESS na iya gabatar da raunuka daban-daban, ciki har da urticaria, eczema, canje-canje na lichenoid, exfoliative dermatitis, erythema, raunuka masu siffar manufa, purpura, blisters, pustules, ko haɗuwa da waɗannan. Ƙunƙarar fata da yawa na iya kasancewa a cikin majiyyaci ɗaya a lokaci guda ko canza yayin da cutar ta ci gaba. A cikin marasa lafiya da fata mai duhu, farkon erythema bazai iya ganewa ba, don haka yana buƙatar bincika a hankali a ƙarƙashin yanayin haske mai kyau. Pustules sun zama ruwan dare a fuska, wuyansa da yankin kirji.

A cikin mai yiwuwa, ingantacciyar Registry Turai na Muhimman Cutaneous Adverse Reactions (RegiSCAR), 56% na marasa lafiya na DRESS sun haɓaka kumburin mucosal mai laushi da yashwa, tare da 15% na marasa lafiya da ke da kumburin mucosal da ke tattare da shafuka masu yawa, galibi oropharynx. girma har ma kafin bayyanar cututtuka na fata. Kurjin yakan wuce fiye da makonni biyu kuma yana da tsawon lokacin farfadowa, lokacin da lalacewa ta zahiri shine babban fasalin. Bugu da ƙari, ko da yake ba kasafai ba, akwai ƙananan marasa lafiya da DRESS waɗanda ƙila ba za su kasance tare da kurji ko eosinophilia ba.

Launuka na DRESS yawanci sun haɗa da jini, hanta, koda, huhu, da tsarin zuciya, amma kusan kowane tsarin gabobin jiki (ciki har da tsarin endocrin, gastrointestinal, neurological, ido, da tsarin rheumatic) na iya shiga ciki. A cikin binciken na RegiSCAR, kashi 36 cikin 100 na marasa lafiya suna da aƙalla wata gabobin da ke da hannu, kuma kashi 56 cikin ɗari suna da gabobin biyu ko fiye. Atypical lymphocytosis shine mafi yawan al'ada kuma farkon rashin lafiyar hematological, yayin da eosinophilia yakan faru a cikin matakan baya na cutar kuma yana iya ci gaba.
Bayan fata, hanta ita ce mafi yawan gaɓoɓin gabbai. Matsakaicin matakan enzyme hanta na iya faruwa kafin kurjin ya bayyana, yawanci zuwa matsakaicin digiri, amma na iya kaiwa lokaci-lokaci har sau 10 mafi girman iyakar al'ada. Mafi yawan nau'in raunin hanta shine cholestasis, sannan kuma gauraye cholestasis da raunin hanta. A lokuta da ba kasafai ba, gazawar hanta na iya zama mai tsanani don buƙatar dashen hanta. A lokuta na DRESS tare da tabarbarewar hanta, mafi yawan nau'in magungunan ƙwayoyin cuta shine maganin rigakafi. Binciken na yau da kullun ya bincika marasa lafiya 71 (babban 67 da yara 4) tare da abubuwan da ke da alaƙa da DRES. Kodayake yawancin marasa lafiya suna da lalacewar hanta a lokaci ɗaya, 1 cikin marasa lafiya 5 suna zuwa tare da keɓantaccen shigar koda. Magungunan rigakafi sune mafi yawan magungunan da ke da alaƙa da lalacewar koda a cikin marasa lafiya DRESS, tare da vancomycin yana haifar da kashi 13 na lalacewar koda, sannan allopurinol da anticonvulsants. Rauni mai tsanani na koda yana da ƙara yawan ƙwayar creatinine ko rage yawan tacewar glomerular, kuma wasu lokuta suna tare da proteinuria, oliguria, hematuria ko duka uku. Bugu da kari, ana iya samun keɓewar hematuria ko proteinuria, ko ma babu fitsari. 30% na marasa lafiya da abin ya shafa (21/71) sun sami maganin maye gurbin renal, kuma yayin da yawancin marasa lafiya suka dawo da aikin koda, ba a sani ba ko akwai abubuwan da suka faru na dogon lokaci. Hannun huhu, wanda ke da gajeriyar numfashi, bushewar tari, ko duka biyun, an ruwaito shi a cikin 32% na marasa lafiya DRESS. Mafi yawan cututtukan huhu a cikin gwajin hoto sun haɗa da shiga tsaka-tsakin tsaka-tsaki, ciwo mai tsanani na numfashi da kuma zubar da jini. Matsalolin sun haɗa da matsananciyar ciwon huhu, ciwon huhu na interstitial lymphocytic, da kuma pleurisy. Tunda DRESS na huhu sau da yawa ana kuskure a matsayin ciwon huhu, ganewar asali yana buƙatar babban matakin taka tsantsan. Kusan dukkan lamuran da suka shafi huhu suna tare da sauran tabarbarewar gabobin jiki. A cikin wani bita na tsari, har zuwa 21% na marasa lafiya DRESS suna da myocarditis. Myocarditis na iya jinkiri na tsawon watanni bayan wasu alamun DRESS sun ragu, ko ma na ci gaba. Nau'o'in sun bambanta daga m eosinophilic myocarditis (remission tare da maganin rigakafi na gajeren lokaci) zuwa m necrotizing eosinophilic myocarditis (mutuwar fiye da 50% da tsaka-tsakin rayuwa na kwanaki 3 zuwa 4 kawai). Marasa lafiya tare da myocarditis sau da yawa suna tare da dyspnea, ciwon kirji, tachycardia, da hypotension, tare da haɓakar matakan enzyme na myocardial na myocardial, canje-canje na electrocardiogram, da rashin daidaituwa na echocardiographic (kamar pericardial effusion, systolic dysfunction, ventricular septal hypertrophy, da biventricular gazawar). Hoto na maganadisu na zuciya na iya bayyana raunin endometrial, amma tabbataccen ganewar asali yawanci yana buƙatar biopsy endometrial. Hannun huhu da na zuciya ya yi ƙasa da yawa a cikin DRESS, kuma minocycline yana ɗaya daga cikin abubuwan da ke haifar da haɓaka.

An inganta tsarin makin rajista na Turai kuma ana amfani da shi sosai don gano cutar DRESS (Table 2). Tsarin maki yana dogara ne akan halaye bakwai: ainihin zafin jiki sama da 38.5 ° C; Girman nodes na lymph aƙalla wurare biyu; Eosinophilia; Lymphocytosis mai lalacewa; Rash (rufe fiye da 50% na sararin saman jiki, halayen halayen halayen dabi'a, ko binciken tarihi wanda ya dace da hawan jini); Hannun gabobin da ba su da lahani; Da kuma tsawaita gafara (fiye da kwanaki 15).
Makin ya fito daga -4 zuwa 9, kuma ana iya raba tabbacin ganowa zuwa matakai huɗu: maki a ƙasa na 2 yana nuna babu cuta, 2 zuwa 3 yana nuna cuta mai yiwuwa, 4 zuwa 5 yana nuna yiwuwar kamuwa da cuta, kuma fiye da 5 yana nuna alamun DRESS. Makin RegiSCAR yana da fa'ida musamman don tabbatar da sake dubawa na yiwuwar lokuta saboda ƙila marasa lafiya ba su cika cika dukkan ka'idojin bincike a farkon cutar ba ko kuma ba su sami cikakkiyar kima mai alaƙa da makin ba.

DRESS yana buƙatar bambanta daga wasu halayen halayen fata masu tsanani, ciki har da SJS da cututtuka masu dangantaka, epidermal necrolysis mai guba (TEN), da m exfoliating impetigo (AGEP) (Figure 1B). Lokacin shiryawa don DRESS yawanci ya fi tsayi fiye da sauran munanan halayen fata. SJS da TEN suna tasowa da sauri kuma yawanci suna warwarewa da kansu a cikin makonni 3 zuwa 4, yayin da alamun DRESS sukan kasance masu tsayi. Kodayake shigar da mucosal a cikin marasa lafiya na DRESS na iya buƙatar bambanta daga SJS ko TEN, raunuka na mucosal na baki a cikin DRESS yawanci suna da sauƙi kuma ƙananan jini. Alamar edema na fata na DRESS na iya haifar da blisters na biyu na catatonic da kuma yashwa, yayin da SJS da TEN suna da cikakkun nau'i na epidermal exfoliation tare da tashin hankali na gefe, sau da yawa yana nuna alamar Nikolsky mai kyau. Sabanin haka, AGEP yakan bayyana sa'o'i zuwa kwanaki bayan bayyanar da miyagun ƙwayoyi kuma yana warware sauri cikin makonni 1 zuwa 2. Kurjin AGEP yana lanƙwasa kuma ya ƙunshi pustules ɗin gabaɗaya waɗanda ba su keɓance ga ɗigon gashi ba, wanda ya ɗan bambanta da halayen DRESS.
Wani bincike mai yiwuwa ya nuna cewa 6.8% na marasa lafiya na DRESS suna da siffofi na duka SJS, TEN ko AGEP, wanda 2.5% an yi la'akari da su suna da mummunar mummunar halayen fata. Amfani da ƙa'idodin tabbatarwa na RegiSCAR yana taimakawa wajen gano waɗannan sharuɗɗan daidai.
Bugu da ƙari, ƙwayar cutar kyanda na kowa yakan bayyana a cikin makonni 1 zuwa 2 bayan bayyanar da miyagun ƙwayoyi (sake bayyanawa yana da sauri), amma ba kamar DRESS ba, waɗannan rashes ba su kasance tare da haɓakar transaminase ba, ƙara yawan eosinophilia, ko tsawon lokacin dawowa daga bayyanar cututtuka. DRESS kuma yana buƙatar bambanta daga sauran wuraren cututtuka, ciki har da hemophagocytic lymphohistiocytosis, vascular immunoblastic T-cell lymphoma, da kuma m cututtuka-da-masu-masu cuta.

Ƙwararrun masana ko jagororin kan maganin DRESS ba a samar da su ba; Shawarwari na jiyya da ake da su sun dogara ne akan bayanan lura da ra'ayin ƙwararru. Nazarin kwatancen don jagorantar jiyya shima ba shi da shi, don haka hanyoyin jiyya ba iri ɗaya bane.
Bayyanar cututtukan da ke haifar da magani
Mataki na farko kuma mafi mahimmanci a cikin DRESS shine ganowa da kuma dakatar da mafi kusantar magani. Ƙirƙirar ginshiƙan magunguna dalla-dalla ga marasa lafiya na iya taimakawa tare da wannan tsari. Tare da jadawali na miyagun ƙwayoyi, likitocin na iya tsara tsarin tsara duk magungunan da ke haifar da cututtuka da kuma nazarin dangantakar ɗan lokaci tsakanin bayyanar miyagun ƙwayoyi da kurji, eosinophilia, da shigar da gabobin jiki. Yin amfani da wannan bayanin, likitoci zasu iya tantance maganin da zai iya haifar da DRESS kuma su daina amfani da wannan maganin cikin lokaci. Bugu da ƙari, likitocin na iya komawa zuwa algorithms da aka yi amfani da su don ƙayyade dalilin miyagun ƙwayoyi don wasu mummunan halayen fata.

Magunguna - glucocorticoids
Glucocorticoids na tsarin su ne hanyoyin farko na haifar da gafarar DRESS da kuma magance sake dawowa. Kodayake kashi na farko na al'ada shine 0.5 zuwa 1 mg / d / kg kowace rana (wanda aka auna a cikin daidai da prednisone), akwai rashin gwajin gwaji na asibiti wanda ke kimanta tasirin corticosteroids don DRESS, da kuma nazarin akan nau'o'i daban-daban da tsarin kulawa. Kada a rage adadin glucocorticoids ba bisa ka'ida ba har sai an sami ingantaccen ingantaccen asibiti, kamar raguwar kurji, eosinophil penia, da maido da aikin gabbai. Don rage haɗarin sake dawowa, ana ba da shawarar a hankali a rage adadin glucocorticoids a cikin makonni 6 zuwa 12. Idan ma'auni na daidaitattun ba ya aiki, to, "shock" glucocorticoid far, 250 MG kowace rana (ko daidai) na kwanaki 3, ana iya la'akari da shi tare da raguwa a hankali.
Ga marasa lafiya da ke da DRESS mai laushi, corticosteroids masu tasiri sosai na iya zama zaɓin magani mai inganci. Misali, Uhara et al. ya ruwaito cewa marasa lafiya 10 DRESS sun murmure cikin nasara ba tare da tsarin glucocorticoids ba. Duk da haka, saboda ba a bayyana ko wane marasa lafiya za su iya guje wa jiyya na tsari ba a amince, ba a ba da shawarar yin amfani da hanyoyin kwantar da hankali ba a matsayin madadin.

Guji maganin glucocorticosteroids da maganin da aka yi niyya
Ga marasa lafiya DRESS, musamman waɗanda ke da babban haɗari ga rikitarwa (kamar cututtuka) daga yin amfani da manyan allurai na corticosteroids, ana iya la'akari da hanyoyin kawar da corticosteroid. Ko da yake an sami rahotanni cewa immunoglobulin na ciki (IVIG) na iya zama tasiri a wasu lokuta, binciken da aka bude ya nuna cewa maganin yana da babban haɗari na mummunar tasiri, musamman ma thromboembolism, wanda ya sa yawancin marasa lafiya su canza zuwa tsarin tsarin glucocorticoid. Yiwuwar ingancin IVIG na iya kasancewa yana da alaƙa da tasirin kawar da ƙwayoyin cuta, wanda ke taimakawa hana kamuwa da cutar hoto ko kuma sake kunna cutar. Duk da haka, saboda manyan allurai na IVIG, bazai dace da marasa lafiya da ciwon zuciya na zuciya, gazawar koda, ko hanta hanta.
Sauran zaɓuɓɓukan magani sun haɗa da mycophenolate, cyclosporin da cyclophosphamide. Ta hanyar hana kunna T cell, cyclosporine yana toshe rubutun kwayoyin halitta na cytokines irin su interleukin-5, don haka rage daukar ma'aikata na eosinophilic da takamaiman magungunan T cell. Wani binciken da ya shafi marasa lafiya biyar da aka bi da su tare da cyclosporine da marasa lafiya na 21 da aka bi da su tare da glucocorticoids na tsarin sun nuna cewa yin amfani da cyclosporine yana da alaƙa da ƙananan ci gaban cututtuka, ingantattun matakan asibiti da gwaje-gwaje, da kuma guntuwar asibiti. Duk da haka, cyclosporine ba a halin yanzu ana la'akari da magani na farko don DRESS. Azathioprine da mycophenolate ana amfani da su musamman don kula da jiyya maimakon jiyya.
An yi amfani da ƙwayoyin rigakafi na monoclonal don magance DRESS. Waɗannan sun haɗa da Mepolizumab, Ralizumab, da benazumab waɗanda ke toshe interleukin-5 da axis mai karɓa, Janus kinase inhibitors (kamar tofacitinib), da anti-CD20 monoclonal antibodies (kamar rituximab). Daga cikin waɗannan hanyoyin kwantar da hankali, ana ɗaukar magungunan anti-interleukin-5 a matsayin mafi dacewa, inganci da amintaccen maganin shigar da su. Tsarin inganci na iya kasancewa yana da alaƙa da farkon haɓakar matakan interleukin-5 a cikin DRESS, wanda galibi ke haifar da takamaiman ƙwayoyin ƙwayoyin cuta na T. Interleukin-5 shine babban mai kula da eosinophils kuma yana da alhakin girma, bambance-bambance, daukar ma'aikata, kunnawa da rayuwa. Ana amfani da magungunan anti-interleukin-5 da yawa don kula da marasa lafiya waɗanda har yanzu suna da eosinophilia ko rashin aikin gabobin bayan amfani da glucocorticoids na tsarin.

Tsawon lokacin magani
Maganin DRESS yana buƙatar zama na musamman sosai kuma a daidaita shi bisa ga ci gaban cuta da amsawar jiyya. Marasa lafiya da DRESS yawanci suna buƙatar asibiti, kuma kusan kashi ɗaya cikin huɗu na waɗannan lokuta suna buƙatar kulawa mai zurfi. A lokacin asibiti, ana ƙididdige alamun majiyyaci kowace rana, ana gudanar da cikakken gwajin jiki, kuma ana lura da alamun dakin gwaje-gwaje akai-akai don tantance sa hannu da canje-canje a cikin eosinophils.
Bayan fitarwa, ana buƙatar kimantawa na mako-mako don saka idanu canje-canje a cikin yanayin da daidaita tsarin kulawa a cikin lokaci. Maimaitawa na iya faruwa ba da daɗewa ba yayin raguwar kashi na glucocorticosteroids ko bayan gafara, kuma yana iya kasancewa a matsayin alama ɗaya ko raunin gabobi na gida, don haka ana buƙatar kulawa da marasa lafiya na dogon lokaci kuma gabaɗaya.