Restricted accessReview articleFirst published online 2021-11
A Systematic Review of Efficacy and Safety of Monotherapy and Combination Therapy With Biologic for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Biologic drugs have the potential to halt the progression of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by decreasing concentrations of tumor necrosis factor-α, a cytokine implicated in epithelial cell death. The objective of this systematic review is to investigate the efficacy and safety of biologic monotherapy and combination therapy for SJS/TEN.
Methods
MEDLINE and EMBASE in OVID were searched on October 28, 2020. Inclusion criteria were original studies containing human participants diagnosed with SJS/TEN and treated with biologics. Studies were excluded if they were literature reviews, systematic reviews, letters to the editor, or conference abstracts.
Results
The 38 articles reviewed included 27 (71.1%) case reports, 6 (15.8%) case series, 3 (7.9%) retrospective reviews, and 2 (5.3%) RCTs. The age range of the included studies was 2 to 85 years, the mean age was 46.4 years. The mean body surface (BSA) across the 38 included articles was 31.0%. The average actual mortality reported within the 38 included articles was 9.2%. Both biologic monotherapy and combination therapy were associated with improved outcomes in SJS/TEN. Furthermore, anti TNF-alpha therapy, specifically etanercept, showed improved outcomes as monotherapy.
Conclusions
Overall, reviewed studies presented a strong case for biologic treatment, both monotherapy and combination use, in SJS/TEN treatment. Based on the number of fatal adverse events observed, biologic monotherapy may be safer compared to combination therapy. Further research with a larger sample size and a randomized control trial design is required.
BarvaliyaM.SanmukhaniJ.PatelT.PaliwalN.ShahH.TripathiC. Drug-induced Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap: a multicentric retrospective study. J Postgrad Med. 2011;57(2):doi:10.4103/0022-3859.8186521654132
2.
Ferrandiz-PulidoC.Garcia-PatosV. A review of causes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Arch Dis Child. 2013;98(12):998-1003.doi:10.1136/archdischild-2013-30371823873883
3.
PavlosR.MallalS.PhillipsE. HLA and pharmacogenetics of drug hypersensitivity. Pharmacogenomics. 2012;13(11):1285-1306.doi:10.2217/pgs.12.10822920398
4.
MockenhauptM. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol. 2011;7(6):803-815.doi:10.1586/eci.11.6622014021
5.
YangM-S.LeeJY.KimJet al. Incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis: a nationwide population-based study using National health insurance database in Korea. PLoS One. 2016;11(11):doi:10.1371/journal.pone.016593327835661
6.
FarhatS.BandayM.HassanI. Antecedent drug exposure aetiology and management protocols in Steven-Johnson syndrome and toxic epidermal necrolysis, a hospital based prospective study. J Clin Diagn Res. 2016;10(1):FC01.doi:10.7860/JCDR/2016/16430.704726894082
FrenchLE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int. 2006;55(1):9-16.doi:10.2332/allergolint.55.917075281
9.
WoolridgeKF.BolerPL.LeeBD. Tumor necrosis factor alpha inhibitors in the treatment of toxic epidermal necrolysis. Cutis. 2018;101(1):E15-21.29529123
10.
ZhangS.TangS.LiS.PanY.DingY. Biologic TNF-alpha inhibitors in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a systemic review. J Dermatolog Treat. 2020;31(1):66-73.doi:10.1080/09546634.2019.157754830702955
11.
WangF.YeY.LuoZ-Y.GaoQ.LuoD-Q.ZhangX. Diverse expression of TNF-α and CCL27 in serum and blister of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clin Transl Allergy. 2018;8(1):doi:10.1186/s13601-018-0199-629713456
12.
SternRS.DivitoSJ. Stevens-Johnson syndrome and toxic epidermal necrolysis: associations, outcomes, and Pathobiology—Thirty years of progress but still much to be done. J Invest Dermatol. 2017;137(5):1004-1008.doi:10.1016/j.jid.2017.01.003
13.
WorswickS.CotliarJ. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options. Dermatol Ther. 2011;24(2):207-218.doi:10.1111/j.1529-8019.2011.01396.x21410610
14.
SchneiderJA.CohenPR. Stevens-Johnson syndrome and toxic epidermal necrolysis: a concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017;34(6):1235-1244.doi:10.1007/s12325-017-0530-y28439852
15.
MoherDLiberatiATetzlaffJAltmanDGPRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):doi:10.1371/journal.pmed.100009719621072
16.
GaviganGM.KanigsbergND.RamienML. Pediatric Stevens-Johnson syndrome/toxic epidermal necrolysis halted by etanercept. J Cutan Med Surg. 2018;22(5):514-515.doi:10.1177/120347541875898929421925
17.
Bastuji-GarinS.FouchardN.BertocchiM.RoujeauJC.RevuzJ.WolkensteinP. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149-153.doi:10.1046/j.1523-1747.2000.00061.x10951229
18.
WellsGA.SheaB.O’ConnelDet al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute; 2011.
19.
HigginsJPT.AltmanDG.GøtzschePCet al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:doi:10.1136/bmj.d592822008217
20.
LeeY-Y.KoJ-H.WeiC-H.ChungW-H. Use of etanercept to treat toxic epidermal necrolysis in a human immunodeficiency virus-positive patient. Dermatologica Sinica. 2013;31(2):78-81.doi:10.1016/j.dsi.2012.06.005
21.
ParadisiA.AbeniD.BergamoF.RicciF.DidonaD.DidonaB. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71(2):278-283.doi:10.1016/j.jaad.2014.04.04424928706
22.
ChahalD.AleshinM.TureganoM.ChiuM.WorswickS. Vaccine-induced toxic epidermal necrolysis: a case and systematic review. Dermatol Online J. 2018;24(1):13030/qt7qn5268s15 Jan 2018.doi:13030/qt7qn5268s29469759
23.
WangC-W.YangL-Y.ChenC-Bet al. Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest. 2018;128(3):985-996.doi:10.1172/JCI9334929400697
24.
WallenbornJ.FischerM. Intensive care in a patient with toxic epidermal necrolysis. Case Rep Crit Care. 2017;2017:1-4.doi:10.1155/2017/324619629225976
25.
WorsnopF.WeeJ.NatkunarajahJ.MoosaY.MarsdenR. Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus. Clin Exp Dermatol. 2012;37(8):879-881.doi:10.1111/j.1365-2230.2012.04357.x22548502
26.
Scott-LangV.TidmanM.McKayD. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31(4):532-534.doi:10.1111/pde.1202923072342
PatmanidisK.SidirasA.DolianitisKet al. Combination of infliximab and high-dose intravenous immunoglobulin for toxic epidermal necrolysis: successful treatment of an elderly patient. Case Rep Dermatol Med. 2012;2012:1-3.doi:10.1155/2012/91531423259092
29.
GaitanisG.SpyridonosP.PatmanidisKet al. Treatment of toxic epidermal necrolysis with the combination of infliximab and high-dose intravenous immunoglobulin. Dermatology. 2012;224(2):134-139.doi:10.1159/00033820222572593
30.
PaquetP.JennesS.RousseauAF.LibonF.DelvenneP.PiérardGE. Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study. Burns. 2014;40(8):1707-1712.doi:10.1016/j.burns.2014.01.02724726294
31.
ChongI.ChaoA. Stevens-Johnson syndrome/toxic epidermal necrolysis and treatment with a biologic: a case report. Perm J. 2017;21:doi:10.7812/TPP/16-06028488978
32.
VivarKL.DeschaineM.MessinaJet al. Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy. J Cutan Pathol. 2017;44(4):381-384.doi:10.1111/cup.1287628000240
33.
FamularoG.Di DonaB.CanzonaF.GirardelliCR.CrucianiG. Etanercept for toxic epidermal necrolysis. Ann Pharmacother. 2007;41(6):1083-1084.doi:10.1345/aph.1K00117456541
34.
Torres-NavarroI.Briz-RedónÁlvaro.Botella-CasasGet al. Accuracy of SCORTEN and ABCD-10 to predict mortality and the influence of renal function in Stevens-Johnson syndrome/toxic epidermal necrolysis. J Dermatol. 2020;47(10):1182-1186.doi:10.1111/1346-8138.1549032856355
35.
DidonaD.PaolinoG.GarcovichS.Caposiena CaroRD.DidonaB. Successful use of etanercept in a case of toxic epidermal necrolysis induced by rituximab. J Eur Acad Dermatol Venereol. 2016;30(10):e83-e84.doi:10.1111/jdv.1333026428058
36.
WojtkiewiczA.WysockiM.FortunaJ.ChrupekM.MatczukM.KoltanA. Beneficial and rapid effect of infliximab on the course of toxic epidermal necrolysis. Acta Derm Venereol. 2008;88(4):420-421.doi:10.2340/00015555-046218709327
HungerRE.HunzikerT.BuettikerU.BraathenLR.YawalkarN. Rapid resolution of toxic epidermal necrolysis with anti-TNF-alpha treatment. J Allergy Clin Immunol. 2005;116(4):923-924.doi:10.1016/j.jaci.2005.06.02916210071
39.
EliadesP.FonsecaM.HarpJ. Use of etanercept in a series of pediatric patients with Stevens-Johnson Syndrome-Toxic epidermal necrolysis spectrum disease. JAMA Dermatol. 2020;156(8):921-922.doi:10.1001/jamadermatol.2019.373132347889
40.
PhamCH.GillenwaterTJ.NagengastE.McCulloughMC.PengDH.GarnerWL. Combination therapy: etanercept and intravenous immunoglobulin for the acute treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis. Burns. 2019;45(7):1634-1638.doi:10.1016/j.burns.2018.12.01831466921
41.
ShenM-H.LiuM-T.ChungW-H.LuC-W. Toxic epidermal necrolysis induced by human herpesvirus 7 treated with a tumor necrosis factor-α inhibitor. J Dermatol. 2020;47(10):1179-1181.doi:10.1111/1346-8138.1549332686137
42.
WangF.GaoX.ChenX.TangX.ChenH.HanJ. Successful treatment of interstitial lung disease related to Stevens-Johnson syndrome/toxic epidermal necrolysis overlap with etanercept: a case report and published work review. J Dermatol. 2019;46(11):1035-1038.doi:10.1111/1346-8138.1505831436331
43.
WangR.ZhongS.TuP.LiR.WangM. Rapid remission of Stevens-Johnson syndrome by combination therapy using etanercept and intravenous immunoglobulin and a review of the literature. Dermatol Ther. 2019;32(4):doi:10.1111/dth.1283230659711
44.
López-GómezV.YarzaR.Muñoz-GonzálezHet al. Ribociclib-Related Stevens-Johnson syndrome: oncologic awareness, case report, and literature review. J Breast Cancer. 2019;22(4):661-666.doi:10.4048/jbc.2019.22.e4431897340
45.
CoulombeJ.BelzileE.DuhamelAet al. Pediatric SJS/TEN subdued by a combination of dexamethasone, cyclosporine, and etanercept. J Cutan Med Surg. 2019;23(5):547-550.doi:10.1177/120347541986107831478770
46.
SibbaldC.PuttermanE.MichelettiR.TreatJ.Castelo-SoccioL. Retrospective review of drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis cases at a pediatric tertiary care institution. Pediatr Dermatol. 2020;37(3):461-466.doi:10.1111/pde.1411832058621
47.
HoltzM.GrimstadF.StricklandJ.Dowlut-McElroyT. 93. vulvovaginal involvement in pediatric Stevens-Johnson syndrome: a case series. J Pediatr Adolesc Gynecol. 2019;32(2):233-234.doi:10.1016/j.jpag.2019.02.095
48.
Al-ShouliS.AbouchalaN.BoguszMJ.Al TufailM.Thestrup-PedersenK. Toxic epidermal necrolysis associated with high intake of sildenafil and its response to infliximab. Acta Derm Venereol. 2005;85(6):534-535.doi:10.1080/0001555051003706216396808
KreftB.LieserU.HaaseR.MarschWC.WohlrabJ. Extensive hypertrophic scarring after toxic epidermal necrolysis in a child. Pediatr Dermatol. 2014;31(4):527-528.doi:10.1111/j.1525-1470.2012.01863.x23025572
52.
JiangY-Y.NguyenGH.JinH-Z.ZengY-P. Methazolamide-induced toxic epidermal necrolysis in a man carrying HLA-B*59:01: successful treatment with infliximab and glucocorticoid. Int J Dermatol. 2018;57(4):494-496.doi:10.1111/ijd.1392429359334
FischerM.FiedlerE.MarschWC.WohlrabJ. Antitumour necrosis factor-alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. Br J Dermatol. 2002;146(4):707-709.doi:10.1046/j.1365-2133.2002.46833.x11966713
56.
FischerG. An unwell patient with a blistering rash. Medicine Today. 2017
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
