Expert Reviewed By: Dr. Brandon Colby MD
Severe cutaneous adverse reactions (SCARs) are a group of life-threatening skin conditions often triggered by medications. These reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DiHS). Genetic factors play a significant role in an individual's susceptibility to SCARs, and recent advancements in genetic testing can help identify those at risk and guide treatment decisions. This article delves into understanding, diagnosing, and using genetic testing for susceptibility to SCARs.
Understanding Severe Cutaneous Adverse Reactions
SCARs are rare but serious skin reactions that can be life-threatening. They often occur as a response to medications such as antiepileptic drugs, antibiotics, and antiviral agents. The exact cause of SCARs remains unclear, but it is believed that genetic factors play a crucial role in determining an individual's susceptibility to these reactions. Studies have identified associations between specific human leukocyte antigen (HLA) genotypes and cytochrome P450 (CYP) gene variants with an increased risk of SCARs [2] [3].
Diagnosing Severe Cutaneous Adverse Reactions
Diagnosing SCARs can be challenging due to their rarity and the wide range of clinical presentations. A thorough medical history, physical examination, and laboratory tests are essential for an accurate diagnosis. In some cases, a skin biopsy may be necessary to confirm the diagnosis. Identifying the causative drug is crucial for proper management, as discontinuing the offending medication can significantly improve the prognosis.
Genetic Testing for Susceptibility to Severe Cutaneous Adverse Reactions
Recent advancements in genetic testing have made it possible to identify individuals at risk of developing SCARs. Genetic testing can detect specific HLA genotypes and CYP gene variants associated with an increased risk of these severe skin reactions. This information can be invaluable for guiding treatment decisions and preventing life-threatening complications.
HLA Genotyping
HLA genotyping is a genetic test that identifies specific HLA alleles associated with an increased risk of SCARs. For example, HLA-B*15:02 and HLA-A*31:01 have been linked to carbamazepine-induced SCARs [4]. HLA genotyping can help determine an individual's risk of developing a severe skin reaction in response to certain medications, allowing healthcare providers to make informed treatment decisions and avoid potentially harmful drugs.
Cytochrome P450 Genotyping
Cytochrome P450 (CYP) enzymes are responsible for metabolizing many medications, and genetic variations in CYP genes can affect drug metabolism and increase the risk of SCARs. CYP2C9 genotyping can help identify individuals at risk of co-trimoxazole-induced SCARs, including SJS/TEN and DRESS in Thai patients [3]. By identifying these genetic variations, healthcare providers can adjust medication doses or select alternative treatments to minimize the risk of severe cutaneous adverse reactions.
Benefits of Genetic Testing for Susceptibility to Severe Cutaneous Adverse Reactions
Genetic testing for SCARs susceptibility offers several benefits, including:
- Improved patient safety by identifying individuals at risk of life-threatening skin reactions
- Guidance for healthcare providers in selecting safer medications and avoiding potentially harmful drugs
- Reduced healthcare costs by preventing severe complications and hospitalizations associated with SCARs
- Increased patient confidence in their treatment plan, knowing that their genetic risk has been considered
In conclusion, understanding, diagnosing, and using genetic testing for susceptibility to severe cutaneous adverse reactions can greatly improve patient outcomes and safety. By identifying individuals at risk and guiding treatment decisions, healthcare providers can minimize the occurrence of these life-threatening skin reactions and provide better care for their patients.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)