Thyrotropin receptor antibodies and a genetic hint in antithyroid drug-induced adverse drug reactions

2018 ◽  
Vol 17 (8) ◽  
pp. 775-784 ◽  
Author(s):  
Lin-Chau Chang ◽  
Chien-Ching Chang ◽  
Pei-Lung Chen ◽  
Shun-Huo Wang ◽  
Yi-Hsuan Chen ◽  
...  
2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-Lang Fan ◽  
Meng-Shin Shiao ◽  
Rosaline Chung-Yee Hui ◽  
Shih-Chi Su ◽  
Chuang-Wei Wang ◽  
...  

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.


2021 ◽  
Vol 22 (12) ◽  
pp. 6480
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Thorsten Mikoteit ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.


Author(s):  
Danilo Villagelin ◽  
Roberto Bernardo Santos ◽  
João Hamilton Romaldini

Context: Graves’ disease is an autoimmune disease caused by thyrotropin receptor antibodies (TRAb). These antibodies can be measured and used for the diagnosis, prediction of remission, and risk of Graves’ orbitopathy development. There are three treatments for Graves’ disease that have remained unchanged for the last 75 years: Antithyroid drugs, radioiodine, and surgery. Antithyroid drugs are the first treatment option worldwide and are usually used for 12 - 18 months. Recent reports suggest the use of antithyroid drugs for more than 18 months with better outcomes. This review focuses on two aspects of treatment with antithyroid drugs: The impact of using antithyroid drugs for more than 12 - 18 months on remission rates and the trend of TRAb during prolonged antithyroid drug treatment. Evidence Acquisition: A review was performed in Medline on the published work regarding the duration of ATD treatment and remission of Graves' disease and also ATD treatment and TRAb status during the 1990 - 2019 period. Results: Remission rates are variable (30% - 80%), and many clinical and genetic factors serve as predictors. The long-term use of antithyroid drugs appears to increase remission rates. TRAb values usually decline during ATD treatment, but the trend could occur in two ways: Becoming negative or showing a fluctuating pattern. However, approximately 10% of the patients will remain TRAb-positive after five years of treatment with antithyroid drugs. Conclusions: Antithyroid drugs can be used for long periods with an increase in remission rates, and a gradual decrease in TRAb levels, with the disappearance of TRAb in 90% of the patients after 60 months.


2014 ◽  
pp. 375-383 ◽  
Author(s):  
Renato Tozzoli ◽  
Marcello Bagnasco ◽  
Danilo Villalta

2020 ◽  
pp. 5752-5760
Author(s):  
Sarah Walsh ◽  
Daniel Creamer ◽  
Haur Yueh Lee

Adverse reactions to medications are common and important cause of iatrogenic illness. Severe cutaneous adverse drug reactions include toxic epidermal necrolysis, Stevens–Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis, which together constitute 2% of all adverse drug reactions and may be life-threatening. Less severe drug-induced skin reactions such as exanthems, urticaria, lichenoid drug rashes, and fixed drug eruptions are more common, sometimes termed benign cutaneous adverse reactions, and generally resolve without sequelae. Drugs may also cause adverse events due to alteration of the normal function of the skin or its appendages. This may take the form of photosensitivity, abnormal pigmentation, or disrupted growth of hair or nails.


1999 ◽  
Vol 45 (3) ◽  
pp. 407-409 ◽  
Author(s):  
Yukihiko Watanabe ◽  
Hisato Tada ◽  
Yoh Hidaka ◽  
Toru Takano ◽  
Keiko Takeoka ◽  
...  

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