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Systemic interventions for treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis: summary of a cochrane review

JAMA Dermatol

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme

Arch Dermatol

Current perspectives on Stevens-Johnson syndrome and toxic epidermal necrolysis

Clin Rev Allergy Immunol

Epidermal Necrolysis (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis)

Update on pathobiology in Stevens-Johnson syndrome and toxic epidermal necrolysis

Dermatol Sin

A review of the systemic treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis

Biomedicines

Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions

Toxins (Basel)

Immunologic mediators in Stevens–Johnson syndrome and toxic epidermal necrolysis

Semin Ophthalmol

Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis

Nat Med

Soluble FAS ligand: a discriminating feature between drug-induced skin eruptions and viral exanthemas

J Invest Dermatol

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Nature

Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis

JAMA Netw Open

Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis

Sci Rep

COVID-19-induced toxic epidermal necrolysis

Clin Exp Dermatol

Case of erythema multiforme/Stevens–Johnson syndrome: an unusual presentation of Covid-19

J R Coll Physicians Edinb

Corona virus disease 2019-associated Stevens-Johnson syndrome: a case report

BMC Ophthalmol

Development of toxic epidermal necrolysis in a coronavirus disease 2019 patient with recurrence of positive SARS-CoV-2 viral RNA

J Dermatol

Stevens-Johnson syndrome as a primary skin manifestation of COVID-19

Postgrad Med J

T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Epstein-Barr virus: the impact of scientific advances on clinical practice

Blood

Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein-Barr virus proteins in oligoarticular juvenile idiopathic arthritis

Arthritis Rheum

The influence of antiviral T-cell responses on the alloreactive repertoire

Immunol Today

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare, potentially life threatening mucocutaneous hypersensitivity reaction resulting in desquamation of the skin and mucosa. These patients are managed on burns units due to the widespread desquamation. We report the largest case series of participants developing SJS/TEN in the setting of recent COVID infection or vaccination. We found a seven-fold increase in SJS/TEN since the COVID pandemic. This increase correlates with an increase in COVID infections and vaccination rates. We explore the immunopathological relationships between COVID and SJS/TEN and propose theories for possible associations.

The seven-fold rise in incidence of Stevens-Johnson syndrome & toxic epidermal necrolysis: Associations with COVID-19 and the vaccine.

The seven-fold rise in incidence of Stevens-Johnson syndrome &amp; toxic epidermal necrolysis: Associations with COVID-19 and the vaccine

JAMA Dermatology

<jats:sec id="ab-doi220074-4"><jats:title>Importance</jats:title><jats:p>Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.</jats:p></jats:sec><jats:sec id="ab-doi220074-5"><jats:title>Objective</jats:title><jats:p>To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.</jats:p></jats:sec><jats:sec id="ab-doi220074-6"><jats:title>Data Sources</jats:title><jats:p>The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.</jats:p></jats:sec><jats:sec id="ab-doi220074-7"><jats:title>Study Selection</jats:title><jats:p>Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.</jats:p></jats:sec><jats:sec id="ab-doi220074-8"><jats:title>Data Extraction and Synthesis</jats:title><jats:p>Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.</jats:p></jats:sec><jats:sec id="ab-doi220074-9"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.</jats:p></jats:sec><jats:sec id="ab-doi220074-10"><jats:title>Results</jats:title><jats:p>Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.</jats:p></jats:sec><jats:sec id="ab-doi220074-11"><jats:title>Conclusion and Relevance</jats:title><jats:p>In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.</jats:p></jats:sec>

Drug causality in Stevens-Johnson syndrome/toxic epidermal necrolysis in Europe: analysis of 10 years RegiSCAR-Study.

Pharmacoepidemiol Drug Saf

Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in United States adults.

The epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK.

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

Long-term physical and psychological outcomes of Stevens-Johnson syndrome/toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs: the EuroSCAR-study.

Clinical, etiologic, and histopathologic features of Stevens-Johnson syndrome during an 8-year period at Mayo Clinic.

Mayo Clin Proc

ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis.

Clin Pharmacol Ther

Stevens-Johnson syndrome and toxic epidermal necrolysis standard reporting and evaluation guidelines: results of a National Institutes of Health working group.

The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis.

Expert Rev Clin Immunol

Recurrence and mortality following severe cutaneous adverse reactions.

JAMA

Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Trends in outpatient antibiotic use and prescribing practice among US older adults, 2011-15: observational study.

Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Br J Dermatol

Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment.

J Am Acad Dermatol

Central limit theorem: the cornerstone of modern statistics.

Korean J Anesthesiol

GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.

Review of culprit drugs associated with patients admitted to the burn unit with the diagnosis of Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome.

Toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in pediatric patients with a focus on newer antiepileptic drugs: a 25-year retrospective study at a single tertiary care center.

Pediatr Dermatol

Retrospective study of patients with SJS/TEN treated at a tertiary burn unit in Canada: overview of 17 years of treatment.

J Cutan Med Surg

A retrospective, 5-year, clinicoepidemiological study of severe cutaneous adverse reactions (SCARs).

Int J Dermatol

Factors predicting the outcome in Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study over a 5-year period.

Severe cutaneous adverse drug reactions: incidence, clinical patterns, causative drugs and modalities of treatment in Assiut University Hospital, Upper Egypt.

Dermatol Ther

The link between HLA-B alleles and causative drugs in Vietnamese patients with Stevens-Johnson syndrome/toxic epidermal necrolysis.

Open Access Maced J Med Sci

Retrospective study of 213 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis from China.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective descriptive study.

A 10-year retrospective cohort study of the management of toxic epidermal necrolysis and Stevens-Johnson syndrome in a New South Wales state referral hospital from 2006 to 2016.

Ocular and mucocutaneous sequelae among survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis in Togo.

Dermatol Res Pract

Stevens-Johnson syndrome and toxic epidermal necrolysis: retrospective review of 10-year experience.

Causative factors and clinical outcome in Steven Johnson syndrome and toxic epidermal necrolysis.

J Postgrad Med Inst

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children: 20 years study in a tertiary care hospital.

World J Pediatr

Genitourinary involvement and management in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

J Pediatr Urol

Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 88 Chinese patients.

Chin Med J (Engl)

Steven Johnson syndrome and toxic epidermal necrolysis in a burn unit: a 15-year experience.

Stevens-Johnson syndrome and toxic epidermal necrolysis: an analysis of triggers and implications for improving prevention.

Am J Med

Severe cutaneous adverse drug reactions in pediatric patients: a multicenter study.

J Allergy Clin Immunol Pract

Stevens-Johnson syndrome and toxic epidermal necrolysis in Dr. Hasan Sadikin General Hospital Bandung, Indonesia from 2009-2013.

Asia Pac Allergy

Risk factors and mortality among patients with severe muco-cutaneous drug reactions.

Dan Med J

A 15-year review of pediatric toxic epidermal necrolysis.

J Burn Care Res

Stevens-Johnson syndrome and toxic epidermal necrolysis: a multi-aspect comparative 7-year study from the People’s Republic of China.

Drug Des Dev Ther

Stevens-Johnson syndrome and toxic epidermal necrolysis: a 20-year single-center experience.

Stevens-Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africa: a multicentric study in four countries.

An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

Indian J Dermatol Venereol Leprol

Toxic epidermal necrolysis: five years of treatment experience from a burn unit.

SCORTEN and impaired renal function related to mortality of toxic epidermal necrolysis syndrome patients in the Asian population.

J Eur Acad Dermatol Venereol

Causes and treatment outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in 82 adult patients.

Korean J Intern Med

Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

Pediatrics

Epidemiological study of Stevens-Johnson syndrome and toxic epidermal necrolysis: retrospective analysis of Southern Taiwanese population during 2002 to 2007.

Zhonghua Pifuke Yixue Zazhi

Seasonal variation of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with trimethoprim-sulfamethoxazole.

Combination therapy of intravenous immunoglobulin and corticosteroid in the treatment of toxic epidermal necrolysis and Stevens-Johnson syndrome: a retrospective comparative study in China.

Cutaneous adverse drug reactions: a 9-year study from a south Indian hospital.

A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century.

J Burn Care Rehabil

Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum.

Ophthalmology

Stevens-Johnson syndrome and toxic epidermal necrolysis in Thailand.

The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyell’s syndrome).

Assessment of treatment approaches and outcomes in Stevens-Johnson syndrome and toxic epidermal necrolysis: insights from a pan-European multicenter study.

Stevens-Johnson syndrome and toxic epidermal necrolysis—retrospective review of cases in a high complexity hospital in Brazil.

Aetiopathogenesis of severe cutaneous adverse reactions (SCARs) in children: a 9-year experience in a tertiary care paediatric hospital setting.

Clin Exp Allergy

Severe cutaneous adverse reactions: a single-center retrospective study of 173 patients in China.

Ann Dermatol

Stevens Johnson syndrome and toxic epidermal necrolysis—an Australian analysis of treatment outcomes and mortality.

J Dermatolog Treat

Steven-Johnson syndrome and toxic epidermal necrolysis at a tertiary care centre in South India: a 12 year retrospective analysis.

J Pakistan Assoc Dermatol

An epidemiological study of Stevens-Johnson syndrome and toxic epidermal necrolysis during 2010-2015 at Shahid Faghihi hospital, Shiraz, Iran.

Iran J Med Sci

Stevens-Johnson syndrome/toxic epidermal necrolysis: a multicenter retrospective study of 377 adult patients from the United States.

Trends in culprit drugs and clinical entities in cutaneous adverse drug reactions: a retrospective study.

Cutan Ocul Toxicol

Characterization of Stevens-Johnson syndrome and toxic epidermal necrolysis among patients admitted to Kenyatta National Hospital: a retrospective cross-sectional study.

Drugs Real World Outcomes

Drug-induced Stevens-Johnson syndrome in Indian population: a multicentric retrospective analysis.

Niger J Clin Pract

Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients—treatment and outcome.

Allergol Int

Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992-2012.

Asian Biomed

Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional analysis of patients in an integrated allergy repository of a large health care system.

Retrospective analysis of corticosteroid treatment in Stevens-Johnson syndrome and/or toxic epidermal necrolysis over a period of 10 years in Vajira Hospital, Navamindradhiraj University, Bangkok.

Clinical profiles of Stevens-Johnson syndrome among Thai patients.

Factors associated with increased mortality in a predominantly HIV-infected population with Stevens Johnson syndrome and toxic epidermal necrolysis.

PLoS One

Severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap in children, a 10 years survey.

Eur J Pediatr Dermatol

Toxic epidermal necrolysis and Stevens-Johnson syndrome in South Africa: a 3-year prospective study.

Drug-induced Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap: a multicentric retrospective study.

J Postgrad Med

Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia.

Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: a retrospective study of causative drugs and clinical outcome.

Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management.

Cornea

Carbamazepine—the commonest cause of toxic epidermal necrolysis and Stevens-Johnson syndrome: a study of 7 years.

A 10-year experience with toxic epidermal necrolysis.

Stevens-Johnson syndrome in children.

Pediatr Infect Dis

Distinguishing case series from cohort studies.

Ann Intern Med

Global antibiotic consumption and usage in humans, 2000-18: a spatial modelling study.

Lancet Planet Health

A systematic review of Stevens-Johnson syndrome and/or toxic epidermal necrolysis over a period of 20 years in Thailand.

J Med Assoc Thai

Severe cutaneous adverse drug reactions of Chinese inpatients: a meta-analysis.

An Bras Dermatol

Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions.

Pharmacogenet Genomics

Association of HLA-A*11:01 with sulfonamide-related severe cutaneous adverse reactions in Japanese patients.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

J Allergy Clin Immunol

Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction.

Lancet

Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.

Clin Infect Dis

Cotrimoxazole: rationale for re-examining its indications for use.

Drug Saf

Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.
To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.
The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.
Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.
Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.
Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.
In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis.

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

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