Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians

Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 78-86 ◽  
Author(s):  
Chun-Bing Chen ◽  
Yi-Hsin Hsiao ◽  
Tony Wu ◽  
Mo-Song Hsih ◽  
Wichittra Tassaneeyakul ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Drug Dosage ◽  
Clinical Severity ◽  
Chinese Patients ◽  
Stevens Johnson Syndrome ◽  
Research Database ◽  
Predictive Values ◽  
Asian Populations ◽  
Incidence And Mortality ◽  
Cutaneous Adverse Reactions

Objective:To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai).Methods:We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)–induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database.Results:We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6  drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10−10; odds ratio 27.90; 95% confidence interval [CI] 7.84–99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077–0.584).Conclusions:Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

2019 ◽  
Vol 25 (36) ◽  
pp. 3872-3880 ◽  
Author(s):  
Marcel M. Bergmann ◽  
Jean-Christoph Caubet
Keyword(s):  
Adverse Reactions ◽  
Lymphocyte Transformation ◽  
Stevens Johnson Syndrome ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Patch Tests ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

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.

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.

CTNI-52. RETROSPECTIVE ANALYSIS OF USING RADIOTHERAPY WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATING FIELDS FOR CHINESE PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi72-vi72
Author(s):  
Yang Wang ◽  
Jingsong Wu ◽  
Zhiyong Qin ◽  
Enmin Wang ◽  
Yu Yao ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adverse Reactions ◽  
Treatment Time ◽  
Synergistic Effects ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Transducer Array ◽  
Nccn Guidelines ◽  
Tumor Treating Fields ◽  
Cutaneous Adverse Reactions

Abstract OBJECTIVES Tumor Treating Fields (TTFields) has been shown to improve the overall survival of newly diagnosed GBM (ndGBM) when combined with Temozolomide (TMZ) in the EF-14 trial. Preclinical studies suggested synergistic effects between TTFields and radiotherapy. This study is aimed to examine the safety and efficacy of combination therapy (chemoradiation concurrent with TTFields treatment) for ndGBM patients in China. METHODS From July 2020 to May 2021, 33 ndGBM patients were treated with combination therapy (radiation target volume following NCCN guidelines). Eight patients had transducer array removed during radiotherapy, others retained transducer array on scalp. All patients had assessment every two months by MRI scan. The adverse reactions and monthly compliance data for TTFields treatment were recorded. RESULTS Twenty-five patients have completed the combination therapy. Three patients retained transducer array during radiotherapy but did not limit the scalp dose (mean: 21.7Gy). As a result, Grade 2 cutaneous adverse reactions developed, and TTFields treatment was suspended. Four patients suspended TTFields treatment due to other adverse reactions. The remaining patients who had limited scalp doses (mean &lt; 20Gy) had no suspension or delay in combination therapy due to cutaneous adverse reactions. The median time of TTFields treatment during radiotherapy is 21.24 hours/day (IQR:19.26,22.08). Two patients had progressive disease, 1 died of pulmonary infection, and 30 had stable disease. The incidence of cutaneous AE was 48.5% (16/33), Grade1: 27.2% (9/33), Grade 2: 21.2% (7/33), and Grade 3: 3% (1/33). CONCLUSIONS The combination therapy was well tolerated in Chinese patients with ndGBM. Removing transducer array during radiotherapy may increase the frequency of array replacement while reducing the patient's daily treatment time. However, retaining transducer array will increase cutaneous adverse reactions. Scalp dose limitation is required yet it allows a maximum duration of TTFields. Further follow-ups are ongoing.

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.

rs9263726 is a specific genetic marker for allopurinol-induced severe cutaneous adverse reactions in Chinese patients

2015 ◽  
Vol 12 (6) ◽  
pp. 585-592 ◽  
Author(s):  
Zhiyao Chen ◽  
Shichao Zhang ◽  
Jingjing Zhang ◽  
Yan Zhang ◽  
Ling Xue ◽  
...  
Keyword(s):  
Genetic Marker ◽  
Adverse Reactions ◽  
Chinese Patients ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

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 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.

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