Pharmacogenetic Testing for Prevention of Severe Cutaneous Adverse Drug Reactions

Chang, Chi-Jen; Chen, Chun‐Bing; Hung, Shuen‐Iu; Ji, Chao; Chung, Wen‐Hung

doi:10.3389/fphar.2020.00969

Cited by 45 publications

(58 citation statements)

References 110 publications

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“…Severe cutaneous adverse drug reactions (SCAR) such as the epidermal necrolysis characteristic of the Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the morbilliform exanthematous rash with the systemic involvement characteristic of drug-induced hypersensitivity syndrome (DIHS) are classified as delayed type (type-IV) hypersensitivity reactions [ 1 ]. Type IV hypersensitivity reactions are characterized by the activation of CD4 and CD8 lymphocytes and often develop 7 days to several weeks after drug exposure [ 1 ]. Many studies have elucidated an interaction between human leukocyte antigen (HLA) and drugs in inducing T-cell receptor (TCR) signaling and subsequent lymphocyte activation.…”

Section: Introductionmentioning

confidence: 99%

“…There are several examples of specific HLA alleles associated with SCAR. Notably, carbamazepine and lamotrigine, commonly used anticonvulsant drugs, are associated with SCAR in patients of Asian ethnicity and the HLA-B*15:02 allele and in patients of European ancestry and the HLA-A*31:01 allele [ 1 ]. Similarly, the presence of the HLA-B*57:01 allele is associated with abacavir DIHS [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Notably, carbamazepine and lamotrigine, commonly used anticonvulsant drugs, are associated with SCAR in patients of Asian ethnicity and the HLA-B*15:02 allele and in patients of European ancestry and the HLA-A*31:01 allele [ 1 ]. Similarly, the presence of the HLA-B*57:01 allele is associated with abacavir DIHS [ 1 ]. In all these examples, pre-emptive screening has been shown to reduce the incidence of SCAR [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, the presence of the HLA-B*57:01 allele is associated with abacavir DIHS [ 1 ]. In all these examples, pre-emptive screening has been shown to reduce the incidence of SCAR [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Allopurinol-induced SCAR is associated with the presence of the HLA-B*58:01 allele [ 1 ]. Pre-emptive screening for the HLA-B*58:01 allele has been shown to reduce the incidence of SCAR in new users of allopurinol in Europe, Asia and the US [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

Ikediobi

Schneider

2021

JPM

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Severe cutaneous adverse drug reactions (SCAR) such as the Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DIHS) can be induced by a plethora of medications. The field of pharmacogenomics aims to prevent severe adverse drug reactions by using our knowledge of the inherited or acquired genetic risk of drug metabolizing enzymes, drug targets, or the human leukocyte antigen (HLA) genotype. Dermatologists are experts in the diagnosis and management of severe cutaneous adverse drug reactions (SCAR) in both the inpatient and outpatient setting. However, most dermatologists in the US have not focused on the prevention of SCAR. Therefore, this paper presents a case series and review of the literature highlighting salient examples of how dermatologists can apply pharmacogenomics in the diagnosis and especially in the prevention of SCAR induced by allopurinol and sulfamethoxazole/trimethoprim, two commonly prescribed medications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

Ikediobi

Schneider

2021

JPM

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Race and Pharmacogenomics—Personalized Medicine or Misguided Practice?

Goodman

Brett

2021

JAMA

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The use of race in clinical decision-making is coming under increasing scrutiny, in part because of growing recognition that race-based diagnosis and treatment reflect flawed social, biological, and genetic assumptions. Despite this concern, guidelines, algorithms, and advisory and regulatory bodies (including the US Food and Drug Administration [FDA]) regularly use race in ways that influence clinical decisions. For example, race-based "corrections" have been deemed problematic in algorithms, risk scores, and physiologic calculations used in cardiology, nephrology, urology, and obstetrics. 1,2 Pharmacogenomics is a field that explores relationships between genes and drug effects, with potential to "personalize" medical therapy. For clinical scenarios in which a genotype is clearly linked to important outcomes, direct genetic testing would appear to obviate the need to use race as a surrogate for genetic predisposition in decision-making. However, pharmacogenomics research often invokes race to stratify genetic risk: The assumption is that racial categories can sufficiently distinguish populations with high or low prevalences of certain genes, allowing clinicians to identify

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Evaluation of ProspectiveHLA-B*13:01Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

Liu¹,

Wang²,

Bao³

et al. 2019

JAMA Dermatol

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; and the Dapsone Hypersensitivity Syndrome Prevention Working Group IMPORTANCE Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. OBJECTIVE To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. EXPOSURES Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. RESULTS Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10 −5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. CONCLUSIONS AND RELEVANCE Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

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Pharmacogenetic Testing for Prevention of Severe Cutaneous Adverse Drug Reactions

Cited by 45 publications

References 110 publications

Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

Race and Pharmacogenomics—Personalized Medicine or Misguided Practice?

Evaluation of ProspectiveHLA-B*13:01Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

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