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Medicina (Kaunas, Lithuania) Aug 2021Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare diseases that are characterized by widespread epidermal necrosis and sloughing of skin. They... (Review)
Review
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare diseases that are characterized by widespread epidermal necrosis and sloughing of skin. They are associated with significant morbidity and mortality, and early diagnosis and treatment is critical in achieving favorable outcomes for patients. In this scoping review, Excerpta Medica dataBASE and PubMed were searched for publications that addressed recent advances in the diagnosis and management of the disease. Multiple proteins (galectin 7 and RIP3) were identified that are promising potential biomarkers for SJS/TEN, although both are still in early phases of research. Regarding treatment, cyclosporine is the most effective therapy for the treatment of SJS, and a combination of intravenous immunoglobulin (IVIg) and corticosteroids is most effective for SJS/TEN overlap and TEN. Due to the rare nature of the disease, there is a lack of prospective, randomized controlled trials and conducting these in the future would provide valuable insights into the management of this disease.
Topics: Adrenal Cortex Hormones; Cyclosporine; Humans; Immunoglobulins, Intravenous; Skin; Stevens-Johnson Syndrome
PubMed: 34577817
DOI: 10.3390/medicina57090895 -
F1000Research 2020Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane.... (Review)
Review
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane. SJS/TEN are considered to be on the same spectrum of diseases with different severities. They are classified by the percentage of skin detachment area. SJS/TEN can also cause several complications in the liver, kidneys, and respiratory tract. The pathogenesis of SJS/TEN is still unclear. Although it is difficult to diagnose early stage SJS/TEN, biomarkers for diagnosis or severity prediction have not been well established. Furthermore, optimal therapeutic options for SJS/TEN are still controversial. Several drugs, such as carbamazepine and allopurinol, are reported to have a strong relationship with a specific human leukocyte antigen (HLA) type. This relationship differs between different ethnicities. Recently, the usefulness of HLA screening before administering specific drugs to decrease the incidence of SJS/TEN has been investigated. Skin detachment in SJS/TEN skin lesions is caused by extensive epidermal cell death, which has been considered to be apoptosis via the Fas-FasL pathway or perforin/granzyme pathway. We reported that necroptosis, i.e. programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, and its interaction with the formyl peptide receptor 1 induce necroptosis. Several diagnostic or prognostic biomarkers for SJS/TEN have been reported, such as CCL-27, IL-15, galectin-7, and RIP3. Supportive care is recommended for the treatment of SJS/TEN. However, optimal therapeutic options such as systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-α antagonists are still controversial. Recently, the beneficial effects of cyclosporine and TNF-α antagonists have been explored. In this review, we discuss recent advances in the pathophysiology and management of SJS/TEN.
Topics: Apoptosis; Epidermis; Humans; Necrosis; Stevens-Johnson Syndrome
PubMed: 32595945
DOI: 10.12688/f1000research.24748.1 -
Psychopharmacology Bulletin Mar 2021Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The... (Review)
Review
Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.
Topics: Anticonvulsants; Carbamazepine; HLA-B Antigens; Humans; Lamotrigine; Stevens-Johnson Syndrome; United States
PubMed: 34092825
DOI: No ID Found -
Orphanet Journal of Rare Diseases Dec 2010Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes.... (Review)
Review
Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP), disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS). Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease.
Topics: Asian People; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; HLA-B Antigens; Humans; Stevens-Johnson Syndrome
PubMed: 21162721
DOI: 10.1186/1750-1172-5-39 -
JAMA Dermatology Apr 2023Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
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.
OBJECTIVE
To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.
DATA SOURCES
The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.
STUDY SELECTION
Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.
DATA EXTRACTION AND SYNTHESIS
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.
MAIN OUTCOMES AND MEASURES
Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.
RESULTS
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.
CONCLUSION AND RELEVANCE
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.
Topics: Humans; Stevens-Johnson Syndrome; Anti-Bacterial Agents; Prevalence; Sulfanilamide; Retrospective Studies
PubMed: 36790777
DOI: 10.1001/jamadermatol.2022.6378 -
Acta Bio-medica : Atenei Parmensis Jan 2019Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be considered a late-onset allergic reaction, can cause serious long-term sequelae.... (Review)
Review
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be considered a late-onset allergic reaction, can cause serious long-term sequelae. SJS/TEN are considered a spectrum of life-threatening adverse drug reactions. They have the same clinical manifestations and the only difference is in the extent of epidermal detachment. These conditions are associated with high mortality, although incidence of SJS/TEN is rare in children. SJS/TEN is an adverse drug reaction influenced by genes that involve pharmacokinetics, pharmacodynamics and immune response. Infective agents are additional influencing factors. Anticonvulsants and antibiotics, and especially sulphonamides and non-steroidal anti-inflammatory drugs, are among the drugs that were predominantly suspected of triggering SJS/TEN. No evidence-based standardized treatment guidelines for SJS or TEN are currently available. The usual treatment is mainly founded on the withdrawal of the suspected causative agent and supportive therapy. In pediatric patients, the specific therapeutic strategies are controversial and comprise systemic corticosteroids and the use of intravenous immunoglobulin (IVIG). More recently, new therapeutic approaches have been used, such as immunosuppressive therapies, including cyclosporine and TNF-α inhibitors.
Topics: Child; Humans; Stevens-Johnson Syndrome
PubMed: 30830062
DOI: 10.23750/abm.v90i3-S.8165 -
Journal of Plastic, Reconstructive &... Jun 2016The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson...
The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to.
Topics: Adult; Diagnosis, Differential; Disease Management; Evidence-Based Practice; Humans; Patient Acuity; Practice Guidelines as Topic; Skin; Stevens-Johnson Syndrome; United Kingdom
PubMed: 27287213
DOI: 10.1016/j.bjps.2016.01.034 -
Skin Therapy Letter Sep 2022Toxic epidermal necrolysis (TEN) is an immune mediated, severe cutaneous adverse drug reaction characterized by epidermal detachment affecting greater than 30% body... (Review)
Review
Toxic epidermal necrolysis (TEN) is an immune mediated, severe cutaneous adverse drug reaction characterized by epidermal detachment affecting greater than 30% body surface area. The mortality rate of TEN exceeds 20% and is usually caused by infection and respiratory compromise. Withdrawal of the causative drug, supportive care, and adjuvant therapy improve prognosis. Over the past decade, randomized controlled trials and meta-analyses have supported a role for cyclosporine, tumor necrosis factor alpha inhibitors, and combination therapy with intravenous immune globulin and corticosteroids. This review summarizes the medical management of TEN in adult patients.
Topics: Adult; Humans; Stevens-Johnson Syndrome; Immunoglobulins, Intravenous; Cyclosporine; Adrenal Cortex Hormones; Immunologic Factors
PubMed: 36469487
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Sep 2021Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is... (Review)
Review
Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive care, topical and/or systemic steroids, and, recently, cyclosporine, the mainstay of management involves identifying and discontinuing the causative drug. This review article will provide an overview of FDE with an emphasis on its generalized bullous variant.
Topics: Diagnosis, Differential; Drug Eruptions; Humans; Recurrence; Skin; Stevens-Johnson Syndrome
PubMed: 34577848
DOI: 10.3390/medicina57090925 -
Revista Da Associacao Medica Brasileira... 2016Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These... (Review)
Review
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs). Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal.
Topics: Humans; Prognosis; Risk Assessment; Risk Factors; Skin; Stevens-Johnson Syndrome
PubMed: 27656858
DOI: 10.1590/1806-9282.62.05.468