Back to Search
Start Over
Analysis of HLA-B Allelic Variation and IFN-γ ELISpot Responses in Patients with Severe Cutaneous Adverse Reactions Associated with Drugs.
- Source :
-
The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2019 Jan; Vol. 7 (1), pp. 219-227.e4. Date of Electronic Publication: 2018 May 22. - Publication Year :
- 2019
-
Abstract
- Background: The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult.<br />Objective: To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs.<br />Methods: A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured.<br />Results: The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia and systemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the "probable" category based on the Naranjo algorithm scale, as the culprit drugs.<br />Conclusions: HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.<br /> (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Alleles
Allopurinol adverse effects
Allopurinol therapeutic use
Anticonvulsants adverse effects
Anticonvulsants therapeutic use
Cells, Cultured
Drug Hypersensitivity immunology
Drug Hypersensitivity Syndrome
Drug-Related Side Effects and Adverse Reactions immunology
Enzyme-Linked Immunospot Assay
Female
Genetic Association Studies
Humans
Lymphocyte Activation
Male
Middle Aged
Polymorphism, Genetic
Skin Diseases immunology
Thailand
beta-Lactams adverse effects
beta-Lactams therapeutic use
Drug Hypersensitivity genetics
Drug-Related Side Effects and Adverse Reactions genetics
Genotype
HLA-B Antigens genetics
Interferon-gamma metabolism
Leukocytes, Mononuclear immunology
Skin Diseases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2213-2201
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The journal of allergy and clinical immunology. In practice
- Publication Type :
- Academic Journal
- Accession number :
- 29800753
- Full Text :
- https://doi.org/10.1016/j.jaip.2018.05.004