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      Incidence, causative drugs, and economic consequences of drug-induced SJS, TEN, and SJS–TEN overlap and potential drug–drug interactions during treatment: a retrospective analysis at an Indonesian referral hospital

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          Abstract

          Background

          Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening adverse drug reactions (ADRs) that are commonly caused by medications. Apart from their contribution to morbidity and mortality, these diseases may also present substantial consequences on health care resources. In this study, we aimed to identify the incidence, causative drugs, and economic consequences of these serious ADRs and potential drug–drug interactions (DDIs) during treatment.

          Methods

          A retrospective study that included 150 patients diagnosed with drug-induced SJS, SJS–TEN overlap, and TEN, from 2009 to 2013 in a referral hospital in West Java Province, Indonesia, was conducted to analyze the causative drugs, cost of illness (COI) as a representation of economic consequences, and potential DDIs during treatment.

          Results

          The results showed that analgesic–antipyretic drugs were the most frequently implicated drugs. The COIs for SJS, SJS–TEN overlap, and TEN patients were 119.49, 139.21, and 162.08 US dollars per day, respectively. Furthermore, potential DDIs with several therapeutic medications and corticosteroids used to treat SJS, SJS–TEN overlap, and TEN were also identified.

          Conclusion

          This study showed that analgesic–antipyretic was the major causative drug which contributed to SJS, SJS–TEN overlap, and TEN. Furthermore, our results also showed that SJS, SJS–TEN overlap, and TEN may cause considerable financial consequences to patients.

          Most cited references35

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

          To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.
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            ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis.

            Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case-control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case-control analysis had described as "probably not associated" and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case-control analysis results, can be considered a reference tool in SJS/TEN.
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              Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel.

              Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions. We sought to update knowledge on the causes of SJS or TEN with a focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN. We conducted a multinational case-control study. In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2017
                21 July 2017
                : 13
                : 919-925
                Affiliations
                [1 ]Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy
                [2 ]Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia
                Author notes
                Correspondence: Rizky Abdulah, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung Sumedang KM 21, Jatinangor 45363, Indonesia, Tel/fax +62 22 779 6200, Email r.abdulah@ 123456unpad.ac.id
                Article
                tcrm-13-919
                10.2147/TCRM.S142226
                5533485
                40a8bb2c-6ca1-4b63-8ccf-c56955883e34
                © 2017 Abdulah et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Original Research

                Medicine
                stevens–johnson syndrome,toxic epidermal necrolysis,adverse drug reactions,cost of illness

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