Restricted accessReview articleFirst published online 2025-11
Rapid review of drug induced Stevens Johnson Syndrome case reports from 2003 to 2023: Trends among monoclonal antibodies and systemic immunosuppressant therapy
Drug-induced Steven-Johnson Syndrome (SJS) is a life-threatening hypersensitivity reaction and systemic steroid immunosuppressant therapy is not universally recommended. With the changing landscape of new drugs, it is important to determine emerging trends in this severe drug induced adverse event.
Objective
The objectives were to examine drug induced SJS case reports published from January 1 2003 to December 31 2023 for emerging trends of drugs implicated and systemic immunosuppressant therapy administered.
Methods
Literature search was done using PubMed (MEDLINE) database with keywords and Boolean terms, “Stevens Johnson Syndrome” AND “Case Report,” filtered for the time period of interest, articles available free and in English. Included case reports were only studies in which a single drug was implicated.
Results
Forty-nine case reports met inclusion criteria and critical analysis of quality rated studies from moderate to strong; however, causality assessment instrument was only reported for 10 (20%) case reports. There was equal distribution by sex; patient ages ranged from 2 to 95 years and 34 (69.4%) case reports originated from countries of the Asian continent. Most common drug implicated was carbamazepine, 5 (10.2%); pembrolizumab was implicated in 4 of 9 case reports involving monoclonal antibody drugs. Thirty-seven patients (75.5%) received systemic steroid immunosuppressant therapy. Two patients (4.1%) died during the clinical course.
Conclusion
The published case reports are predominately from countries known to be at higher risk of drug induced SJS and the emerging greater number of case reports implicating pembrolizumab may be an important safety concern, needing further investigation. Systemic steroid use was the preferred immunosuppressant therapy.
Ardern-JonesMRFriedmannPS. Skin manifestations of drug allergy. Br J Clin Pharmacol2011; 71(5): 672–683.
2.
SekulaPDunantAMockenhauptM, et al.Comprehensive survival analysis of a cohort of patients with Stevens–Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol2013; 133(5): 1197–1204.
3.
HaanenJCarbonnelFRobertC, et al.Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol2017; 28: iv119–iv142.
4.
ThompsonJASchneiderBJBrahmerJ, et al.Management of immunotherapy-related toxicities, version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw2019; 17(3): 255–289.
5.
JacobsenAOlabiBLangleyA, et al.Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome. Cochrane Database Syst Rev2022; 3(3): CD013130.
6.
ThongBY-H. Drug-induced Stevens Johnson syndrome and toxic epidermal necrolysis: interpreting the systematic reviews on immunomodulatory therapies. Asia Pac Allergy2023; 13(2): 72–76.
7.
WangLVargheseSBassirF, et al.Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review of PubMed/MEDLINE case reports from 1980 to 2020. Front Med2022; 9: 949520.
8.
FeiWShenJCaiH. Causes of drug-induced severe cutaneous adverse reaction epidermal necrolysis (EN): an analysis using FDA adverse event reporting System (FAERS) database. Clin Cosmet Investig Dermatol2023; 16: 2249–2257.
9.
KardileVKulkarniANadarB, et al.Monoclonal antibodies in oncology: a decade of novel options. Cell Biochem Biophys2023; 81(3): 395–408.
10.
GarrittyCGartlehnerGNussbaumer-StreitB, et al.Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews. J Clin Epidemiol2021; 130: 13–22.
11.
KellyWNArellanoFMBarnesJ, et al.Guidelines for submitting adverse event reports for publication. Pharmacoepidemiol Drug Saf2007; 16(5): 581–587.
12.
AgbabiakaTBSavovićJHarrisR, et al.The development of a tool to assess the quality of case reports of adverse events. Int J Risk Saf Med2008; 20(3): 123–133.
13.
FernandoSL. The management of toxic epidermal necrolysis. Australas J Dermatol2012; 53(3): 165–171.
14.
Armijo-OlivoSStilesCRHagenNA, et al.Assessment of study quality for systematic reviews: a comparison of the Cochrane collaboration risk of bias tool and the effective public health practice project quality assessment tool: methodological research. J Eval Clin Pract2012; 18(1): 12–18.
15.
PageMJMcKenzieJEBossuytPM, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj2021; 372: n71.
ArokeDTchouakamDNAwungiaAT, et al.Ivermectin induced Steven–Johnsons syndrome: case report. BMC Res Notes2017; 10: 1–4.
18.
DengMChaiHYangM, et al.Stevens-Johnson syndrome caused by enzalutamide: a case report and literature review. Front Oncol2021; 11: 736975.
19.
JawaroTKumarAPistunO, et al.Stevens-Johnson syndrome associated with chlordiazepoxide. J Pharm Technol2018; 34(2): 82–85.
20.
PaikSPalASenS, et al.A suspected case of Efavirenz-induced Stevens–Johnson syndrome. Drug Saf Case Rep2015; 2: 1–5.
21.
ShakyaPSharma NepalA. Daunorubicin induced Stevens-Johnson syndrome: a case report. Clin Case Rep2021; 9(7): e04475.
22.
SrinivasanSKarthikeyanESivaneswariS, et al.Clinical condition and medication therapy of amoxicillin-induced Stevens-Johnson syndrome: a case report. Aging Med2019; 2(4): 227–229.
23.
TranHTNguyenKVVercueilL. Successful treatment of a paroxysmal kinesigenic dyskinesia patient with carbamazepine-induced Stevens-Johnson syndrome using oxcarbazepine monotherapy: a case report. Case Rep Neurol2022; 13(3): 598–604.
24.
VenkateswaranNKhianeyRGenerosoA. Stevens johnson syndrome in a patient with giant cell arteritis during short term tocilizumab therapy. Cureus2020; 12(4): e7662.
25.
AkıncıBSivişZŞahinA, et al.Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report. Arch Argent Pediatr2018; 116(3): e459–e462.
26.
Al-BarzinjiNJalalAM. Hydroxychloroquine-induced stevens–johnson syndrome in the patient with systemic lupus erythematosus: a case report in Kurdish region-Iraq. Mediterr J Rheumatol2023; 34(4): 547–549.
27.
AlsulamiSAldahasiMAljabriHM, et al.Drug-induced stevens-johnson syndrome without skin manifestations: a case report and review of literature. Cureus2023; 15(3): e36318.
28.
BaeHMParkYJKimYH, et al.Stevens-johnson syndrome induced by carbamazepine treatment in a patient who previously had carbamazepine induced pruritus-a case report. Korean J Pain2013; 26(1): 80–83.
29.
BatoolSVoloshynaDUsamaM, et al.The Co-existence of agranulocytosis and stevens-johnson syndrome (SJS) in carbamazepine therapy: a case report. Cureus2022; 14(9): e28917.
30.
BekenBCanCÖrencikA, et al.Oxcarbazepine-induced Stevens–Johnson syndrome: a pediatric case report. Oxf Med Case Reports2017; 2017(6): omx028.
31.
CaoJLiQZhiX, et al.Pembrolizumab-induced autoimmune Stevens-Johnson syndrome/toxic epidermal necrolysis with myositis and myocarditis in a patient with esophagogastric junction carcinoma: a case report. Transl Cancer Res2021; 10(8): 3870–3876.
32.
CastanaORempelosGAnagiotosG, et al.Stevens-Johnson syndrome: a case report. Ann Burns Fire Disasters2009; 22(3): 147–151.
33.
ChirasuthatPChayavichitsilpP. Atezolizumab-induced Stevens-Johnson syndrome in a patient with non-small cell lung carcinoma. Case Rep Dermatol2018; 10(2): 198–202.
34.
CravensMGShermanNSawayaJ. Ciprofloxacin-induced Stevens-Johnson syndrome with grapefruit juice consumption: a case report. Cureus2019; 11(1): e3827.
35.
DasJKMedhiJChakravartyR, et al.Mucous membrane grafting for the post-Steven–Johnson syndrome symblepharon: a case report. Indian J Ophthalmol2011; 59(3): 231–233.
36.
DavoodiLJafarpourHKazeminejadA, et al.Hydroxychloroquine-induced Stevens–Johnson syndrome in COVID-19: a rare case report. Oxf Med Case Reports2020; 2020(6): omaa042.
37.
DiepDAluriBCraneA, et al.Stevens-Johnson syndrome in a patient of color: a case report and an assessment of diversity in medical education resources. Cureus2022; 14(2): e22245.
38.
Gracia-CazañaTPadgettECaldereroV, et al.Nivolumab-associated Stevens-Johnson syndrome in a patient with lung cancer. Dermatol Online J2021; 27(3): 13030/qt2897t6dq.
39.
GuiM-ZNiMYinX-D, et al.Ibuprofen induced Stevens-Johnson syndrome and liver injury in children: a case report. Transl Pediatr2021; 10(6): 1737–1742.
40.
HirakiAAoeKMurakamiT, et al.Stevens-Johnson syndrome induced by paclitaxel in a patient with squamous cell carcinoma of the lung: a case report. Anticancer Res2004; 24(2C): 1135–1138.
41.
KandilAODvorakTMignanoJ, et al.Multifocal Stevens-Johnson syndrome after concurrent phenytoin and cranial and thoracic radiation treatment, a case report. Radiat Oncol2010; 5: 1–5.
42.
KhanAARashidFKhanFU, et al.Diagnosis and treatment of flurbiprofen-induced Stevens–Johnson syndrome: a rare case report. Clin Case Rep2022; 10(9): e6365.
43.
KhorAHLimKTanC, et al.Cross-reactivity in AED-induced severe cutaneous adverse reaction: a case report. J Investig Allergol Clin Immunol2016; 26(5): 329–331.
44.
KurianCJDesaiARaffertyW, et al.Case report: alpelisib-induced stevens–johnson syndrome. Front Oncol2022; 12: 954027.
45.
LiXLiGChenD, et al.Case Report: sintilimab-induced Stevens-Johnson Syndrome in a patient with advanced lung adenocarcinoma. Front Oncol2023; 13: 912168.
46.
LinL-CLaiP-CYangS-F, et al.Oxcarbazepine-induced Stevens-Johnson syndrome: a case report. Kaohsiung J Med Sci2009; 25(2): 82–86.
47.
López-GómezVYarzaRMuñoz-GonzálezH, et al.Ribociclib-related stevens-johnson syndrome: oncologic awareness, case report, and literature review. J Breast Cancer2019; 22(4): 661–666.
48.
MachidaMYamazakiCKoudaN, et al.A case report involving suppressed nuclear receptor transcription factors 4a1 and Stevens-Johnson syndrome induced by a single dose of pembrolizumab and successfully treated with early steroid administration, resulting in complete remission of stage III lung cancer. J Pharm Health Care Sci2022; 8(1): 29.
49.
MishraMSinghGGaurA, et al.Lip synechiae: a rare complication of azithromycin-associated Stevens–Johnson syndrome. Natl J Maxillofac Surg2019; 10(2): 232–234.
50.
MkhoyanAHashmiMFKhanF, et al.Stevens-Johnson syndrome: a case report of possible cephalosporin-induced cutaneous adverse reaction. J Infect Dev Ctries2023; 17(10): 1493–1496.
51.
NakamuraROchiFChisakaT, et al.Acetaminophen‐induced Stevens–Johnson syndrome with lethal lung injury: a case report. Clin Case Rep2022; 10(9): e6294.
52.
PaikSSenSDasJ, et al.Allopurinol induced stevens - johnson syndrome - a case report. J Clin Diagn Res2015; 9(2): Wj01–Wj02.
53.
RajputRSagariSDurgavanshiA, et al.Paracetamol induced Steven-Johnson syndrome: a rare case report. Contemp Clin Dent2015; 6(Suppl 1): S278–S281.
54.
SalamaMLawranceIC. Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease. World J Gastroenterol2009; 15(35): 4449–4452.
55.
SandhuMBinodKBhandariJ, et al.Pembrolizumab-associated Stevens-Johnson syndrome in a patient with metastatic non-small cell lung cancer: a case report. Cureus2023; 15(7):e41439.
56.
ShabrawishiMQanashSA. Bronchiolitis obliterans after cefuroxime-induced Stevens-Johnson syndrome. Am J Case Rep2019; 20: 171–174.
57.
SharmaSSharmaNYeolekarM. Oxcarbazepine-induced Stevens Johnson syndrome: a rare case report. Indian Dermatol Online J2011; 2(1): 13–15.
58.
ShawBMaddenMCrespoA, et al.A rare case of severe stevens-johnson syndrome triggered by topical Ofloxacin. Am J Case Rep2023; 24: e941992.
59.
ShettySRChatraLShenaiP, et al.Stevens-Johnson syndrome: a case report. J Oral Sci2010; 52(2): 343–346.
60.
ShresthaABShresthaSYadavPK, et al.Cefixime induced Steven Johnson syndrome: a case report from Bangladesh. Ann Med Surg2022; 79: 104089.
61.
WuJ-YKangKYiJ, et al.Pembrolizumab-induced Stevens-Johnson syndrome in advanced squamous cell carcinoma of the lung: a case report and review of literature. World J Clin Cases2022; 10(18): 6110–6118.
62.
WuM-KChungWWuC-K, et al.The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report. Neuropsychiatr Dis Treat2015; 11: 1039–1041.
63.
XuLZhuYYuJ, et al.Nursing care of a boy seriously infected with Steven–Johnson syndrome after treatment with azithromycin: a case report and literature review. Medicine2018; 97(1): e9112.
64.
Yasui-FurukoriNHashimotoKTsurugaK, et al.Comorbidity of Stevens–Johnson syndrome and neutropenia associated with lamotrigine: a case report. Gen Hosp Psychiatry2014; 36(6): e9–e11.
65.
Rahim AiAIbrahimMISalim FnA, et al.Health information engagement factors in Malaysia: a content analysis of facebook use by the ministry of health in 2016 and 2017. Int J Environ Res Publ Health2019; 16(4): 591.
66.
Arrieta-BolañosEHernández-ZaragozaDIBarqueraR. An HLA map of the world: a comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II. Front Genet2023; 14: 866407.
67.
ChanSLJinSLohM, et al.Progress in understanding the genomic basis for adverse drug reactions: a comprehensive review and focus on the role of ethnicity. Pharmacogenomics2015; 16(10): 1161–1178.
68.
TsuchikamaKAnamiYHaSYY, et al.Exploring the next generation of antibody-drug conjugates. Nat Rev Clin Oncol2024; 21(3): 203–223.
EllisSRVierraATMillsopJW, et al.Dermatologic toxicities to immune checkpoint inhibitor therapy: a review of histopathologic features. J Am Acad Dermatol2020; 83(4): 1130–1143.
71.
GrünwaldPMockenhauptMPanzerR, et al.Erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis - diagnosis and treatment. J Dtsch Dermatol Ges2020; 18(6): 547–553.
72.
ChangH-CWangT-JLinM-H, et al.A review of the systemic treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis. Biomedicines2022; 10(9): 2105.
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