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

Lee, Erika Yue; Knox, Christopher; Phillips, Elizabeth

doi:10.1001/jamadermatol.2022.6378

Cited by 29 publications

(30 citation statements)

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“…4 Circulating anti-Dp I and II antibodies in the sera, and dense IgG deposits in the intercellular spaces and cytoplasmic membrane of epidermal cells have also been demonstrated in SJS/TEN patients. 8 Anti-Dp I and Dp II antibodies from EM/SJS/TEN patients react with fragmented Dp I and II proteins but not with intact Dps. 25 These findings overall suggest that CD8+ cytotoxic T-cells may expose Dp I/II intracellular proteins, in effect priming the environment for a humoral immune response and further epitope spreading.…”

Section: Discussionmentioning

confidence: 99%

“…Dp I and II antibodies induce EM/SJS/TEN‐like skin lesions when injected into the skin of mice 4 . Circulating anti‐Dp I and II antibodies in the sera, and dense IgG deposits in the intercellular spaces and cytoplasmic membrane of epidermal cells have also been demonstrated in SJS/TEN patients 8 . Anti‐Dp I and Dp II antibodies from EM/SJS/TEN patients react with fragmented Dp I and II proteins but not with intact Dps 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Dp autoantibodies may then bind to the cell surface of keratinocytes, become internalized by plasmalemmal vesicles, and attach to desmosomal plaques to exert pathogenic effects 26 . Though existing studies are limited, 11 of 20 patients with EM major and 11 of 13 patients with SJS/TEN have had anti‐Dp antibodies identified in known studies to date 3,6–8,25 …”

Section: Discussionmentioning

confidence: 99%

“…Desmoplakin (Dp) I and II are intracellular, desmosomal plaque proteins responsible for the assembly of intermediate keratin filaments and subsequent attachment to other structural components of desmosomes 3–7 . Prior studies have demonstrated Dp I and II autoantibodies in patients with EM/SJS/TEN, with some proposing that these antibodies may play a pathogenic role via disruption of Dp 3–9 . Loss of Dp I/II immunoreactivity may distinguish EM/SJS/TEN from other histopathologic mimickers, including cGVHD 9 .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7] Prior studies have demonstrated Dp I and II autoantibodies in patients with EM/SJS/TEN, with some proposing that these antibodies may play a pathogenic role via disruption of Dp. [3][4][5][6][7][8][9] Loss of Dp I/II immunoreactivity may distinguish EM/SJS/TEN from other histopathologic mimickers, including cGVHD. 9 We aimed to further assess the use of Dp I/II immunohistochemical stain in discriminating skin biopsy specimens from patients with EM/SJS/TEN from those with cGVHD.…”

Section: Introductionmentioning

confidence: 99%

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Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis spectrum disorders

Irwin,

Yeung,

Shinohara

2023

J Cutan Pathol

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Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis spectrum disorders

Irwin,

Yeung,

Shinohara

2023

J Cutan Pathol

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Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions

Lee,

Gomes,

Drucker

et al. 2024

JAMA

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ImportanceSerious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes.ObjectivesTo explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them.Design, Setting, and ParticipantsNested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.ExposureVarious classes of oral antibiotics.Main Outcomes and MeasuresConditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.ResultsDuring the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.Conclusion and RelevanceCommonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

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Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

Gu,

Shih,

Geevasinga

et al. 2024

JAMA Dermatol

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ImportanceThe HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia.ObjectiveTo evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy.Design, Setting, and ParticipantsA model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023.InterventionNo HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers.Main Outcomes and MeasuresLife-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios.ResultsHLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, −A$83 to A$374; US$76; 95% CI, −US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, −0.0247 to −0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations.Conclusions and RelevanceThe results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

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

Cited by 29 publications

References 100 publications

Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis spectrum disorders

Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis spectrum disorders

Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

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