scholarly journals Real-time clinical note monitoring to detect conditions for rapid follow-up: A case study of clinical trial enrollment in drug-induced torsades de pointes and Stevens-Johnson syndrome

2020 ◽  
Author(s):  
Sarah DeLozier ◽  
Peter Speltz ◽  
Jason Brito ◽  
Leigh Anne Tang ◽  
Janey Wang ◽  
...  
Keyword(s):  
Real Time ◽  
Adverse Drug Events ◽  
Text Processing ◽  
Processing System ◽  
Torsades De Pointes ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Large Hospital ◽  
Automated Method ◽  
Johnson Syndrome

Abstract Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms.

An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

2019 ◽  
Vol 2 (2) ◽  
pp. 1-17
Author(s):  
Sue-Mian Then ◽  
Azman Ali Raymond
Keyword(s):  
Single Gene ◽  
Hypersensitivity Syndrome ◽  
Allelic Frequency ◽  
Stevens Johnson Syndrome ◽  
Case Control Studies ◽  
Drug Induced ◽  
Hla Alleles ◽  
Exfoliative Dermatitis ◽  
Johnson Syndrome ◽  
Systemic Symptoms

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainly on the type of seizure. However, the use of AEDs may also lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discovered that the HLA-B*15:02 allele was strongly associated with carbamazepine (CBZ)-induced SJS/TEN among Han Chinese and this led to the discovery of other HLA alleles and cytochrome P450 (CYP) genes that were significantly associated with various AED-induced cADRs across various populations.  This mini review is an update on the latest findings of the involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamitrogine (LTG) in different case-control studies around the world. From our review, we found that CBZ- and PHT-induced cADRs were more commonly reported than the other AEDs. Therefore, there were more robust pharmacogenetics studies related to these AEDs. OXC- and LTG-induced cADRs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported HLA alleles with these AEDs. It is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for AED-induced cADR.

Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

2020 ◽  
Author(s):  
Dinh van Nguyen ◽  
Hieu Chi Chu ◽  
Christopher Vidal ◽  
Richard B Fulton ◽  
Nguyet Nhu Nguyen ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Surrogate Marker ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Strongly Correlated ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

scholarly journals Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis; Extensive Review of Reports of Drug-Induced Etiologies, and Possible Therapeutic Modalities

2018 ◽  
Vol 6 (4) ◽  
pp. 730-738 ◽  
Author(s):  
Adegbenro Omotuyi John Fakoya ◽  
Princess Omenyi ◽  
Precious Anthony ◽  
Favour Anthony ◽  
Precious Etti ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Toxic Epidermal Necrolysis ◽  
Stevens Johnson Syndrome ◽  
Hypersensitivity Reactions ◽  
Extensive Review ◽  
Drug Induced ◽  
Therapeutic Modalities ◽  
Johnson Syndrome ◽  
Mucous Membranes ◽  
Degrees Of Severity

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles information on the details of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, the pathophysiology, therapeutic management, and largely considers the drug-induced etiologies associated with these conditions.

scholarly journals DRUG INDUCED DERMATOLOGICAL REACTION OF THE 100 MOST COMMONLY PRESCRIBED MEDICATIONS IN UK HOSPITALS

2019 ◽  
pp. 54-57
Author(s):  
MOHAMMED AL-ABADIE ◽  
FARIS OUMEISH ◽  
MOHAMMED AL-RUBAYE ◽  
DINA AL-ABADIE ◽  
PATRICK ANTHONY BALL ◽  
...  
Keyword(s):  
United Kingdom ◽  
Side Effects ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
The United Kingdom ◽  
Johnson Syndrome ◽  
Medication Side ◽  
Drug Adverse Reaction ◽  
Skin Conditions ◽  
Dermatological Side Effects

Objective: It is commonly reported that medicines have side effects related to dermatological practice. However, it is extremely difficult to establish how commonly, or rarely skin-related medication side effects occur. Common dermatological side effects include rash, pruritus, and photosensitivity. Objective: To demonstrate the dermatological side-effects of the most commonly prescribed medications in the United Kingdom. Methods: This paper discusses dermatological side-effects of the commonly prescribed medications, including uncommon or rare manifestations such as angioedema and Stevens - Johnson syndrome (SJS). The list used for the most frequently prescribed drugs in the United Kingdom was created by nurses. This list was compared to the British National Formulary to demonstrate the reported frequency of occurrence of dermatological side-effects or complications. Conclusion: The top 100 prescribed medication cause a number of dermatological side effects that need to be considered when they are prescribed to patients who have pre-existing skin conditions. Additionally, when confronted with a common dermatological problem in any patient, clinicians should always consider the possibility of a drug adverse reaction.

scholarly journals Causative drugs and HLA-B polymorphism in drug-induced Stevens-Johnson syndrome - toxic epidermal necrolysis: A study in five hospitals in Jakarta

2019 ◽  
Author(s):  
Anesia Tania ◽  
Evita Halim Effendi ◽  
Inge Ade Krisanti ◽  
Yulia Ariani
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Drug Eruption ◽  
Stevens Johnson Syndrome ◽  
Allele Polymorphism ◽  
Exclusion Criteria ◽  
Drug Induced ◽  
Causative Drug ◽  
Johnson Syndrome ◽  
Luminex Technology ◽  
Referral Hospitals

Stevens-Johnson syndrome and toxic epidermal necrolysis is a very rare but lifethreatening form of cutaneous drug eruption. In recent years, several countries in Asia had succeded in preventing carbamazepine induced SJS/TEN by screening for HLA-B*15:02 before prescribing carbamazepine. This study aimed to acquire data regarding causative drugs and HLA-B allele polymorphism in SJS/TEN patient in Jakarta. We acquired data from 5 referral hospitals from March 2015 to March 2017. Subject fulfilling the inclusion and exclusion criteria was interviewed and blood sample was taken for DNA extraction. The DNA was examined with PCR SSOP and Luminex technology for high resolution HLA-B typing. We studied 22 subjects. The median age was 45,4 years old (14-74). The most common causative drug in this study is carbamazepine. HLA-B*15:02 and HLAB* 18:01 were the most common allele in all subjects. HLA-B*15:02 was found in five (72%) out of seven subjects whose condition was caused by carbamazepine. The most common causative drug of SJS/TEN in five hospitals in Jakarta is carbamazepine, with five (72%) out seven subjects had HLA-B*15:02 allele.

scholarly journals Overlapping DRESS and Stevens-Johnson Syndrome: Case Report and Review of the Literature

2017 ◽  
Vol 9 (2) ◽  
pp. 1-7 ◽  
Author(s):  
Aneline Casagranda ◽  
Mariano Suppa ◽  
Florence Dehavay ◽  
Véronique del Marmol
Keyword(s):  
Diagnostic Criteria ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Systemic Symptoms ◽  
The Right ◽  
Exanthematous Pustulosis ◽  
Cutaneous Adverse Reactions

Drug-induced severe cutaneous adverse reactions (SCARs) include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), and epidermal necrolysis (Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis). The identification of the causal drug is crucial in order to avoid further exposure, but making the right differential diagnosis of the type of SCAR is equally important since treatment, follow-up, and prognosis of different SCARs are not the same. These syndromes are distinct entities with different clinical, biological, and histological patterns, but sometimes the early distinction between 2 SCARs can be extremely challenging, and overlapping conditions could therefore be taken into consideration, although true overlapping SCARs are very rare when using strict diagnostic criteria (described by the RegiSCAR group). Only a better understanding of the physiopathology of the SCARs could possibly explain these ambiguities and overlaps. We report a case of SCAR in an 86-year-old patient probably induced by allopurinol and simultaneously fulfilling the diagnostic criteria for DRESS and SJS, thus considered as an overlapping case of SCARs.

scholarly journals Drug-induced liver injury associated with stevens-Johnson syndrome/toxic epidermal necrolysis: Patient characteristics, causes, and outcome in 36 cases

Hepatology ◽  
2015 ◽  
Vol 63 (3) ◽  
pp. 993-999 ◽  
Author(s):  
Harshad Devarbhavi ◽  
Sujata Raj ◽  
Venu H. Aradya ◽  
Vijaykumar T. Rangegowda ◽  
Girish P. Veeranna ◽  
...  
Keyword(s):  
Liver Injury ◽  
Toxic Epidermal Necrolysis ◽  
Patient Characteristics ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Johnson Syndrome

Drug-Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Call for Optimum Patient Stratification and Theranostics via Pharmacogenomics

2018 ◽  
Vol 19 (1) ◽  
pp. 329-353 ◽  
Author(s):  
Chonlaphat Sukasem ◽  
Theodora Katsila ◽  
Therdpong Tempark ◽  
George P. Patrinos ◽  
Wasun Chantratita
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Clinical Care ◽  
Genomic Medicine ◽  
Stevens Johnson Syndrome ◽  
Future Research ◽  
Great Promise ◽  
Patient Stratification ◽  
Clinical Implementation ◽  
Drug Induced ◽  
Johnson Syndrome

The Global Genomic Medicine Collaborative, a multinational coalition of genomic and policy experts working to implement genomics in clinical care, considers pharmacogenomics to be among the first areas in genomic medicine that can provide guidance in routine clinical practice, by linking genetic variation and drug response. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening reactions to medications with a high incidence worldwide. Genomic screening prior to drug administration is a key opportunity and potential paradigm for using genomic medicine to reduce morbidity and mortality and ultimately eliminate one of the most devastating adverse drug reactions. This review focuses on the current understanding of the surveillance, pathogenesis, and treatment of SJS/TEN, including the role of genomics and pharmacogenomics in the etiology, treatment, and eradication of preventable causes of drug-induced SJS/TEN. Gaps, unmet needs, and priorities for future research have been identified for the optimal management of drug-induced SJS/TEN in various ethnic populations. Pharmacogenomics holds great promise for optimal patient stratification and theranostics, yet its clinical implementation needs to be cost-effective and sustainable.

scholarly journals Stevens–Johnson syndrome and acute vanishing bile duct syndrome after the use of amoxicillin and naproxen in a child

2019 ◽  
Vol 47 (9) ◽  
pp. 4537-4543 ◽  
Author(s):  
Lu Li ◽  
Sujun Zheng ◽  
Yu Chen
Keyword(s):  
Case Report ◽  
Bile Duct ◽  
Epithelial Cells ◽  
Hypersensitivity Reaction ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Vanishing Bile Duct Syndrome ◽  
Johnson Syndrome ◽  
Vanishing Bile Duct ◽  
Duct Syndrome

We present the case report of a 6-year-old patient who developed Stevens–Johnson syndrome (SJS) and acute vanishing bile duct syndrome (VBDS) after taking oral amoxicillin and naproxen. SJS, an immune complex-mediated hypersensitivity reaction involving the skin and mucosa, is usually drug-induced, and it can lead to systemic symptoms. Acute VBDS is rare, often presenting with progressive loss of the intrahepatic biliary tract. VBDS is an immune-mediated bile duct-associated disease, and immunological damage to the bile duct system is an important mechanism for VBDS. Serious drug-induced liver injury (DILI) is also associated with immunity. The drug acts as a hapten with keratin on the surface of biliary epithelial cells. The autoantibodies produced by this action can damage the bile duct epithelial cells and cause the bile duct to disappear. SJS is a serious type of polymorphic erythema that is mainly considered to be a hypersensitivity reaction to drugs, and it may involve multiple factors.  The patient in this case report was treated with glucocorticoids, plasma exchange, ursodeoxycholic acid, and traditional Chinese medicine. He recovered completely within 5 months. This case report indicates that caution should be used because amoxicillin and naproxen can cause SJS and VBDS in children.

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