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.

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.

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 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 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.

scholarly journals Diagnostic Tools and Biomarkers for Severe Drug Eruptions

2021 ◽  
Vol 22 (14) ◽  
pp. 7527
Author(s):  
Manabu Yoshioka ◽  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Drug Eruption ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Diagnostic Tools ◽  
Clinical Aspects ◽  
Drug Eruptions ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.

scholarly journals Genetics of Severe Cutaneous Adverse Reactions

2021 ◽  
Vol 8 ◽  
Author(s):  
Shang-Chen Yang ◽  
Chun-Bing Chen ◽  
Mao-Ying Lin ◽  
Zhi-Yang Zhang ◽  
Xiao-Yan Jia ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adverse Reactions ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Stevens Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Advances in identification of multiple genetic alleles associated with specific drugs related SCARS in different populations is an important breakthrough in recent years for prevention of SCARs. This article summarized the findings on genetic factors related to SJS/TEN, especially for HLA.

Sign in / Sign up

Export Citation Format

Share Document