After plasmapheresis for SJS/TEN be

After plasmapheresis for SJS/TEN became eligible for coverage
by health insurance in 2006, the available options of treatment
modalities have been changing in TEN. Therefore, we separated the
cases by the date of each 7 years before and after this change
(2000e2006 and 2007e2013) and compared the treatment modalities
used and the mortality rates in these 2 periods. From 2000
to 2006, 22 cases of SJS and 17 cases of TEN were evaluated. From
2007 to 2013, 30 cases of SJS and 18 cases of TEN were evaluated.
Although steroid pulse therapy and the combination of IVIG therapy
(

Results (Indonesian) 1:

Setelah Plasmaperesis untuk SJS/sepuluh berhak untuk cakupanoleh asuransi kesehatan pada tahun 2006, pilihan pengobatanmodalitas telah berubah dalam sepuluh. Oleh karena itu, kita dipisahkankasus oleh tanggal setiap 7 tahun sebelum dan setelah perubahan ini(2000e2006 dan 2007e2013) dan dibandingkan modalitas pengobatandigunakan dan kematian harga dalam periode ini 2. Dari tahun 2000hingga 2006, 22 kasus SJS dan 17 kasus sepuluh dievaluasi. Dari2007-2013, 30 kasus SJS dan 18 kasus sepuluh dievaluasi.Meskipun steroid pulsa terapi dan kombinasi terapi IVIG(< 2 g/kg) dengan kortikosteroid terapi yang arus utamasampai tahun 2006, frekuensi kasus diobati dengan kombinasiTerapi Plasmaperesis dan kortikosteroid meningkat sangatsetelah 2007 (ditunjukkan dalam gambar 4).Angka kematian menunjukkan penurunan yang luar biasa setelah 2007,dibandingkan dengan 2000e2006, dari 4,5% 0.0% di SJS dan dari23,5 5.6% di sepuluh, meskipun nilai rata-rata SCORTENagak meningkat setelah 2007 (2.18 dalam 2000e2006 dan di 2.502007e2013). kita dibandingkan mortalitas diperkirakan sepuluhkasus dengan tingkat sebenarnya. Hanya sedikit perbedaan ini ditampilkan dalam2000e2006; tingkat diperkirakan adalah 23,9% (4.1 kasus) dan aktualtingkat adalah 23,5% (4 kasus). Namun, hal ini menunjukkan perbedaan relatif besardi 2007e2013; tingkat diperkirakan adalah 26,5% (4.8 kasus) dansebenarnya tingkat adalah 5.6% (kasus 1). Selain itu, ketika membandingkanSkor rata-rata SCORTEN kasus almarhum bebas antara 2periode, hal ini menunjukkan peningkatan yang relatif besar dari 1,69 untuk 2,47.DiskusiSJS dan sepuluh yang jarang tetapi gangguan mengancam kehidupan. Kematianharga untuk kondisi ini baru-baru ini dilaporkan 34% di1 tahun untuk SJS/sepuluh di Europe18 dan 3% dan 19% untuk SJS dan sepuluh,masing-masing, dalam Japan.19 beberapa penelitian telah mengungkapkan rincian barutentang jalur apoptosis keratinocytes dan Imunologiperubahan yang terkait dengan efek samping obat reaksi dalam penyakit ini.8, 20e23 selain cytotoxicity langsung oleh T sitotoksiksel (CTLs), beberapa larut faktor seperti sebagai faktor nekrosis tumor-a,oksida nitrat, larut Fas ligan (sFasL), granulysin, annexin A1 adalahsekarang dianggap untuk menengahi keratinocyte apoptosis. Abe et al. melaporkandarah perifer yang perlengketan sel (PBMCs) dari SJS /SEPULUH pasien mensekresikan sFasL pada rangsangan dengan obat kausal. DalamSelain itu, mereka menunjukkan bahwa pasien sera menginduksi apoptosis padakeratinocytes berbudaya, menunjukkan bahwa sFasL yang diproduksi oleh PMBCsdapat berkontribusi untuk patogenesis SJS/TEN.21 Chung et al.menjelaskan bahwa granulysin yang diproduksi oleh CTLs atau sel-sel pembunuh alamikonsentrasi dalam cairan blister lesi kulit SJS sepuluh adalah duauntuk empat kali lipat lebih tinggi daripada perforin, granzyme B ataukonsentrasi sFasL, dan depleting granulysin dikurangi cytotoxicitydari keratinocytes. Selain itu, mereka menunjukkan bahwa injeksidari granulysin ke dalam kulit mouse mengakibatkan fiturmeniru SJS-TEN.22 baru saja Saito et al. mengungkapkan kontribusidari annexin A1 di keratinocyte necroptosis dari SJS sepuluh. Penipisanannexin A1 oleh antibodi spesifik berkurang supernatant cytotoxicity.Keratinocytes SJS sepuluh dinyatakan peptida berlimpah formylreseptor 1, reseptor untuk annexin A1, sedangkan kontrol keratinocytestidak. Mereka juga menunjukkan bahwa inhibisi necroptosissepenuhnya dicegah SJS/sepuluh-seperti tanggapan dalam mouse modelSJS/TEN.23Ada ada terapi yang didirikan untuk SJS/sepuluh, meskipun banyakmodalitas pengobatan termasuk kortikosteroid, Plasmaperesis, danIVIG telah digunakan. Tetap tantangan bahwa sangat sulit untukmenilai efikasi pengobatan untuk gangguan seperti serius dan langkadalam uji klinis besar acak terkontrol (RCT).Dalam studi ini, kami disajikan saat ini karakteristik klinisdan perawatan SJS dan sepuluh di 87 pasien dirawat di 2 kamirumah sakit untuk mengevaluasi manfaat dari pengobatanretrospektif.Usia pasien dengan SJS dan sepuluh secara luas didistribusikandari muda hingga tua. Obat-obatan penyebab utama adalah antibiotik,Antikonvulsan, NSAID, dan obat-obatan yang dingin. Dominasiobat ini dalam menyebabkan penyakit yang tampaknya telah berubahkarena Aihara et al. dianalisis 269 kasus SJS dan 287 kasus sepuluhyang dilaporkan sejak tahun 1981 hingga 1997 di Japan.24 Namun, kamistudy, anticonvulsants were more frequently the causative drugsthan has been previously reported in SJS. This might be related tothe fact that in recent years, anticonvulsants have been used notonly for convulsions but also for other diseases, such as neurogenicpain and bipolar disorder.In addition to the severe skin symptoms, many organ involvementswere observed. The organs most commonly involvedwere liver and kidneys. However, while less common than hepatitisand renal dysfunction, respiratory and gastro-intestinal disorderswere severe conditions often resulting in fatality. In addition tomulti-organ involvement, another major problem in the clinicalcourse was secondary infections, especially sepsis.As for treatments, systemic corticosteroid therapy was mainlyused both in SJS and TEN in Japan.25 The use of corticosteroids isbased on the idea that corticosteroids effectively suppress anexcessive immune response. While their use is still controversial,18,26 recent studies have suggested them to be a valid treatmentmodality for SJS/TENS.6,7,27 Tripathi et al. reviewed 67 patients, andonly 1 patient died of causes not related to steroid therapy.6 Theyrecommended the prompt use of high-dose systemic corticosteroidsfor a relatively brief period for the treatment of SJS. Hiraharaet al. evaluated 8 patients treated with methylprednisolone pulse.They reported no deaths among these patients, whereas the predictedmortality was 1.6 deaths according to the SCORTEN scoringsystem (the mean SCORTEN score was 2.1).27In the present study, corticosteroids were used to treat all patientsexcept 3, and many of them were treated with steroid pulsetherapy. The mortality was 6 deaths (6.9%) and all deceased caseswere treated with steroids. However, this mortality was muchlower than the predicted mortality (8.9 deaths, 25.3% in TEN) accordingto the SCORTEN scoring system. As we mentioned in detailabout the 3 deceased TEN cases with sepsis, 2 cases receivedadministration of corticosteroids in inadequate dose. Another 1case with fever of unknown origin was suspected to have had underlyingsystemic infection. Although it is undeniable that corticosteroidsmay facilitate secondary infection, prompt tapering ofthe dose after amelioration of SJS/TENS symptoms was consideredto reduce the risk of fatal adverse effects of the systemiccorticosteroids.In addition to the steroid therapy, plasmapheresis (mostly PE)and IVIG were performed in severe TEN cases. Plasmapheresishas been reported to be effective in several studies of TEN afterthe middle of the 1980s.13,14,28,29 The mechanism of its effectivenessremains speculative, but most likely involves theremoval of drugs and drug metabolites, soluble Fas ligand, andchemical mediators from the blood circulation. In our study, 14patients including 12 TEN with average SCORTEN score 2.58(predicted mortality 3.68 deaths, 30.6%) were treated with
plasmapheresis and only one TEN patient died (mortality rate
7.4%). This data might show the possibility that plasmapheresis is
useful modality in the treatment of refractory TEN after starting
steroid therapy.
IVIG therapy with an acute TEN patient was first reported by
Viard et al. in 1998.8 After that report, many studies have revealed
the effectiveness of IVIG therapy. The mechanisms are suspected to
involve the inhibition of Fas-mediated keratinocyte death by
naturally occurring Fas-blocking antibodies in the administered
immunoglobulins and the inhibition of inflammatory cytokines. In
addition, it has been thought that IVIG works through mechanisms
of inhibition of inflammatory cells and modulation of immune
function in inflammatory diseases.30 However, the effect of IVIG is
still controversial.31,32 In 2006, French et al. summarized the clinical
studies reported and suggested that the use of more than 2 g/kg of
body weight of intravenous immunoglobulin is beneficial on the
mortality associated with TEN.9 Barron et al.33 conducted a metaanalysis
with meta-regression of 13 observational studies conducted
during the period of 1966e2011 to assess IVIG in the
treatment of SJS/TEN based on the SCORTEN scoring system. They
showed that IVIG at doses of 2 g or more/kg appears to significantly
decrease mortality. Chen et al.34 also recommended the use of IVIG
with total doses of more than 2 g/kg for the treatment of SJS/TEN.
They reported that early application of steroids provided beneficial
effects, and that combination therapy with steroids and IVIG
showed better therapeutic effects than did steroids alone. In our
study, 15 patients including 11 TEN with average SCORTEN score
2.09 (predicted mortality 2.59 deaths, 23.6%) were treated with
IVIG and the mortality rate was 13.3% (2 deaths). The total amount
administered was less than 2 g/kg in 13 cases, including 2 deceased
cases administered with a total of 60 g each of IVIG (SCORTEN
scores 4 and 6, respectively). IVIGwas administered in combination
with corticosteroids except in 1 case of TEN with underlying
infection. In 2 of these cases with TEN, plasmapheresis was
additionally performed after IVIG administration because it had not
been effective enough. In addition, since only 2 patients were
treated with IVIG at a dose of more than 2 g/kg in the study period,
we are not able to discuss the efficacy of IVIG in terms of dosedependence.
Taken together, it is difficult to evaluate the additional
effects of IVIG accurately from these data.
In the comparison of the data between 2000e2006 and
2007e2013, it was shown that the average SCORTEN score of the
non-deceased cases rose from 1.69 to 2.47 after 2007 and the
mortality rate fell from 23.