Related Experiment Video
Updated: Mar 21, 2026
07:22
A Standardized Procedure of Dressing Management for Toxic Epidermal Necrolysis
Published on: March 14, 2025
1.3K
Severe cutaneous adverse drug reactions.
Wen-Hung Chung1,2,3,4, Chuang-Wei Wang1,3, Ro-Lan Dao1
1Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Tapei, Linko and Keelung, Taiwan.
The Journal of Dermatology
|May 8, 2016
Summary
Severe cutaneous adverse drug reactions (SCAR) range from mild rashes to fatal conditions. Understanding the complex interplay of human leukocyte antigen (HLA), drug, and T-cell receptor (TCR) interactions is key to developing better prevention and treatment strategies.
Area of Science:
- Immunology
- Pharmacology
- Genetics
Background:
- Drug eruptions present a spectrum from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
- Pathogens can also trigger skin reactions that mimic SCAR.
- Several theoretical models explain the interactions between human leukocyte antigen (HLA), drugs, and T-cell receptors (TCR) in SCAR pathogenesis.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying SCAR.
- To explore the roles of specific HLA-drug associations and T-cell responses in SCAR.
- To investigate the contribution of metabolic factors and genetic variations to SCAR development.
Main Methods:
- Review of existing models for HLA-drug-TCR interactions (hapten/prohapten, p-i concept, altered peptide/TCR repertoire).
- Analysis of molecular checkpoints including specific HLA loci (e.g., HLA-B*15:02, HLA-B*58:01), TCR involvement, T-cell-mediated responses (granulysin, Fas ligand, perforin/granzyme B, cytokines), and cell death pathways (apoptosis, necroptosis).
- Inclusion of metabolic factors such as CYP2C9*3 and renal function in SCAR pathogenesis.
Main Results:
- Specific HLA alleles are strongly associated with particular drug-induced SCAR (e.g., carbamazepine-SJS/TEN with HLA-B*15:02, allopurinol-SCAR with HLA-B*58:01).
- Molecular mechanisms involve specific drug-antigen/HLA interactions, TCR engagement, and the induction of cytotoxic T-cell responses and keratinocyte death.
- Metabolism, including CYP2C9*3 and impaired renal function, significantly contributes to SCAR development.
Conclusions:
- A comprehensive understanding of SCAR molecular mechanisms, encompassing immune and metabolic pathways, is crucial.
- Identifying specific HLA associations and T-cell responses provides insights into SCAR pathogenesis.
- Improved understanding facilitates the development of more effective SCAR therapeutics and prevention strategies.
Related Concept Videos
01:30Drug Toxicity: Allergic Reactions
126
Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial...
126
01:01Hypersensitivity Reactions: Cytolytic Reactions
115
Type II hypersensitivity involves IgG and IgM antibodies targeting cell surface antigens, leading to cell destruction. This can occur through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or acting as opsonins for phagocytosis. When excessive, these reactions cause significant tissue damage.Drug-induced hemolytic anemia is a common example, where drugs like penicillin or cephalosporins bind to red blood cells, forming drug-protein complexes. These complexes...
115
01:27Allergic Drug Reactions
1.6K
Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing...
1.6K
01:29Staphylococcal Skin Infections
19
Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
19
01:00Drug Toxicity: Overview
163
Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
163
01:19Pharmacovigilance
1.9K
Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
1.9K