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 Chemokines in Severe Cutaneous Adverse Reactions (SCARs)

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 847
Author(s):  
Fumi Miyagawa ◽  
Hideo Asada
Keyword(s):  
Adverse Reactions ◽  
Human Herpesvirus ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Migratory Patterns ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Although the incidence of severe cutaneous adverse reactions (SCARs) to medications is very low, SCARs can result in disability or even death if they are not diagnosed and treated properly. As the rapid recognition of SCARs is essential, it is necessary to develop diagnostic markers for them that can also be used to assess severity and predict outcomes in the early phase. In addition, it is important to identify novel therapeutic targets for SCARs. Chemokines are chemotactic cytokines that control the migratory patterns and locations of immune cells and usually exhibit markedly specific associations with certain human diseases. In Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), the Th1-associated chemokines chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 predominate, while in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), the levels of the Th2-associated chemokines chemokine (C-C motif) ligand 17 (CCL17) and CCL22 are markedly elevated. We suggest that the distinct chemokine profiles of SJS/TEN and DIHS/DRESS can be used to aid their differential diagnosis. CXCL10 has also been reported to be associated with the development of long-term sequelae in DIHS/DRESS. This review focuses on the chemokines involved in the pathogenesis and adjuvant diagnosis of SCARs, particularly SJS/TEN and DIHS/DRESS, but also provides a brief overview of SCARs and the chemokine superfamily. As it is being increasingly recognized that an association exists between human herpesvirus 6 (HHV-6) and DIHS/DRESS, the possible roles of the chemokine/chemokine receptor homologs encoded by HHV-6 in the pathogenesis of DIHS/DRESS are also discussed.

Gene expression profiling in allopurinol-induced severe cutaneous adverse reactions in Vietnamese

2020 ◽  
Vol 21 (14) ◽  
pp. 985-994
Author(s):  
Dinh van Nguyen ◽  
Hieu Chi Chu ◽  
Christopher Vidal ◽  
Janet Anderson ◽  
Nguyet Nhu Nguyen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Adverse Reactions ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Drug Rash ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens–Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens–Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.

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 Cephalosporin-Induced Atypical DRESS Syndrome; a Tale of Two Cases

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Ravindranath Brahmadeo Chavan ◽  
Vasudha Abhijit Belgaumkar ◽  
Nitika S. Deshmukh ◽  
Amruta Patil ◽  
Vijay Deepak Joshi
Keyword(s):  
Drug Reaction ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Standard Group ◽  
Erythematous Rash ◽  
Dress Syndrome ◽  
Drug Induced ◽  
Severe Cutaneous Adverse Reactions ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, idiosyncratic subset of drug-induced hypersensitivity syndrome manifesting as skin eruption, fever, lymphadenopathy, hematologic abnormalities, and multi-organ involvement. It presents usually after a latent period of 2 to 6 weeks as a diffuse erythematous rash with systemic symptoms and facial edema. It is now recognized as one of the severe cutaneous adverse reactions (SCAR) associated with high mortality, chiefly because of derangement of renal or liver functions. The cutaneous morphologies can be myriad, encompassing maculopapular, exfoliative dermatitis-like, pustular, erythema multiforme-like, Stevens-Johnson syndrome-like, and toxic epidermal necrolysis-like presentations. Case Presentation: We hereby report two young males who developed pruritic exfoliating erythematous rash after taking cephalosporin with paradoxical worsening despite drug withdrawal. They were diagnosed with ‘atypical DRESS syndrome’ according to the Japanese study group severe cutaneous adverse reactions (J-SCAR) criteria and treated successfully with systemic steroids and emollients. The J-SCAR scoring and the concept of atypical DRESS are useful in situations, where either all clinical and laboratory criteria are not present simultaneously, or typical clinical presentations wherein human herpes virus-6 (HHV-6) reactivation cannot be documented. Conclusions: These two cases were used to illustrate the hitherto obscure concept of atypical DRESS syndrome that presented with compatible clinical features but did not satisfy all the requisite criteria. We also highlight cephalosporins (one of the most commonly prescribed standard group of drugs) as a plausible but infrequently reported cause of this severe adverse cutaneous drug reaction.

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.

The association between HLA-B*15:02 and phenytoin-induced severe cutaneous adverse reactions: a meta-analysis

2021 ◽  
Author(s):  
Thanh Huong Phung ◽  
Khanh Ngoc Cong Duong ◽  
Mac Ardy Junio Gloria ◽  
Thien Khac Nguyen
Keyword(s):  
Drug Reaction ◽  
Adverse Reactions ◽  
Meta Analysis ◽  
Stevens Johnson Syndrome ◽  
Random Effects Model ◽  
Systemic Symptom ◽  
Anticonvulsant Agent ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Aim: Phenytoin (PHT) is a common anticonvulsant agent known for inducing severe cutaneous adverse reactions (SCARs). HLA-B*15:02 as a risk factor of PHT-induced SCARs was reported in numerous studies with inconsistent results. This meta-analysis aimed to establish pooling evidence of this association. Materials & methods: Pooled odds ratios (ORs) with 95% CIs were estimated using a random-effects model. Results: A total of 11 studies on 1389 patients, were included for the analyses. There was a significant association between HLA-B*15:02 and PHT-induced SCAR (pooled OR = 2.29, 95% CI: 1.25–4.19, p = 0.008). Furthermore, there was a significant association regarding Stevens–Johnson syndrome/toxic epidermal necrolysis (OR = 3.63, 95% CI: 2.15–6.13, p < 0.001) but no association regarding drug reaction with eosinophilia and systemic symptom. Conclusion: The results supported the recommendations of HLA-B*15:02 screening before treatment with PHT.

scholarly journals Case Report: Suspected Case of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Overlap Due to Ursodeoxycholic Acid

2020 ◽  
pp. 96-99
Author(s):  
Shatavisa Mukherjee ◽  
Debajyoti Saha ◽  
Shreyashi Dasgupta ◽  
Santanu Kumar Tripathi
Keyword(s):  
Ursodeoxycholic Acid ◽  
Toxic Epidermal Necrolysis ◽  
Adverse Reactions ◽  
Whole Body ◽  
Stevens Johnson Syndrome ◽  
Suspected Case ◽  
Human Bile ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Stevens–Johnson syndrome and toxic epidermal necrolysis are well-known severe cutaneous adverse reactions, with >100 medications previously implicated, most frequently sulfonamide antibiotics. Ursodeoxycholic acid (UDCA), normally present in human bile at a low concentration, is used for the treatment of various cholestatic disorders. Reports of UDCA causing cutaneous complications are, however, rare. The present report describes a suspected case of UDCA-induced Stevens–Johnson syndrome–toxic epidermal necrolysis overlap in a 24-year-old female, admitted with a whole-body maculopapular rash with oromucocutaneous ulceration and skin desquamation. The patient was managed with supportive care, including fluid and electrolyte replacement, corticosteroids, antibiotics, antihistamines, and intravenous Ig. Early identification, prompt intervention with effective care, and support are the key action points in these severe cutaneous adverse reactions.

scholarly journals Dermoscopic Aspects of Cutaneous Adverse Drug Reactions

2021 ◽  
pp. e2021136
Author(s):  
Gabriela Rossi ◽  
André Da Silva Cartell ◽  
Renato Marchiori Bakos
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Acute Generalized Exanthematous Pustulosis ◽  
Johnson Syndrome ◽  
Vascular Structures ◽  
Systemic Symptoms ◽  
Exanthematous Pustulosis ◽  
Cutaneous Adverse Reactions

Background: Little is known about the dermoscopic evaluation of cutaneous adverse drug reactions (CADRs). Objectives: To evaluate the dermoscopic patterns of CADRs and identify those associated with severe cutaneous adverse reactions to drugs (SCARDs). Patients and Methods: Patients included in this study from May 2015 to April 2016 had presented with CADRs. CADR presentation and classification were based on standard criteria. SCARDs included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), overlap SJS/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The dermoscopic features of CADRs were described and compared according to the severity of the reactions. Results: Sixty-nine patients were included. Sixteen patients (23.2%) presented SCARDs. The main dermoscopic findings in SJS, overlap SJS/TEN and TEN were black dots or necrotic areas (100%). Erosion [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1 (100%)], necrotic borders [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1, (100%)] and epidermal detachment [respectively, 5/6 (83.3%); 2/3 (66.7%) and 1/1 (100%)] were also common among these reactions. Erythema and purpuric dots were the main dermoscopic findings [respectively, 5/6 (83.3%) and 4/6 (66.7%)] in DRESS. In non-severe reactions, the most prevalent structures were erythema and purpura in exanthema [respectively, 31/33 (93.9%) and 24/33 (72.7%)] and erythema and vascular structures in urticarial reactions [respectively, 6/6 (100%) and 3/6 (50%)]. Black dots or necrotic areas, epidermal detachment, necrotic borders and erosion were highly associated with SCARDs (P < 0.001). Conclusions: Dermoscopy improves clinical recognition of SCARDs.

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