GenotypingHLAalleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

Abstract

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests. Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Associations of HLA genetic variants with carbamazepine‐induced cutaneous adverse drug reactions: An updated meta‐analysis

“…Cutaneous adverse drug reactions (cADRs) such as Stevens−Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), and drug reaction with eosinophilia and systemic symptoms (DRESS) are life‐threatening hypersensitivity reactions affecting predominantly the mucous membranes and skin 1–3 . The incidence of cADRs is generally found to be low, but the mortality rates associated with cADRs are high enough (SJS ~1–5%, TEN ~25–35%, DRESS ~10%) to be clinically concerning as reported elsewhere 4 . Medication use (~80% of cases) is one of the most identified and widely accepted reasons for developing life‐threatening cADRs.…”

“… 1 , 2 , 3 The incidence of cADRs is generally found to be low, but the mortality rates associated with cADRs are high enough (SJS ~1–5%, TEN ~25–35%, DRESS ~10%) to be clinically concerning as reported elsewhere. 4 Medication use (~80% of cases) is one of the most identified and widely accepted reasons for developing life‐threatening cADRs. Although different medications such as allopurinol, phenytoin, abacavir, dapsone, flucloxacillin, and cotrimoxazole have been strongly associated with cADRs, carbamazepine (CBZ) is the most studied and causes SJS/TEN in a considerable proportion of patients.…”

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

“…The future of pharmacogenomics-guided therapy in clinical settings across Thailand appears promising because of the availability of evidence of clinical validity of the pharmacogenomics testing (Sukasem et al, 2021a). The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-theart laboratory; multidisciplinary team approach, and healthcare provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomic tests and reimbursement (Jantararoungtong et al, 2021a).…”

Differences in beta-lactam and penicillin allergy: Beyond the West and focusing on Asia-Pacific

“…Reasons for these observed regional variations are likely multifactorial, whether it be more robust electronic health record documentation ( 37 ), or genuine biological ethnic-specific differences. Historically, certain high-risk HLA alleles were identified to be associated with carbamazepine and allopurinol-induced drug allergy among Asian patients, but not BL or anti-microbials ( 38 , 39 ). Interestingly, a recent Thai study found HLA-B*48:01 to be associated with immediate-type reactions to BL, whereas HLA-C*04:06, HLA-C*08:01 and HLA-DRB1*04:06 were associated with delayed reactions ( 40 ).…”