This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "drug_hypersensitivity_scar#Cytotoxic Mediator Release and Keratinocyte Death"). Conforming nodes should substitute the drug-specific culprit and its HLA risk allele (e.g. HLA-B*58:01/allopurinol, HLA-B*15:02/carbamazepine, HLA-B*57:01/abacavir) while preserving the conserved HLA-restricted presentation → cytotoxic T-cell activation → keratinocyte death → epidermal necrolysis → mucocutaneous failure chain. The key conformance / central-effector target is "drug_hypersensitivity_scar#Cytotoxic Mediator Release and Keratinocyte Death".
HLA-Restricted Drug Presentation to Drug-Specific T Cells
trigger
The conserved initiating lesion is immunological recognition of the drug: the drug or its metabolite is presented in an HLA class I-restricted manner to drug-specific T cells (via hapten, p-i, or altered-peptide mechanisms). Risk arises from the combination of drug structure/metabolism, HLA alleles, and the T-cell receptor repertoire — a type IV (delayed) hypersensitivity reaction.
Downstream
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Drug-Specific Cytotoxic T-Cell and NK-Cell Activation
HLA-restricted presentation activates and expands drug-specific cytotoxic lymphocytes.
Show evidence (2 references)
"acute TEN is considered a T-cell mediated, type IV hypersensitivity disorder. It mostly results from a cumulative effect of risks from the drug structure, drug metabolism, HLA alleles and T cell clonotypes."
Frames SCAR as a type IV hypersensitivity driven by the combination of drug structure/metabolism, HLA alleles, and T-cell clonotypes — the insult-agnostic trigger of this module. Evidence source is OTHER because this is a review article.
"immune synapse composed of cytotoxic T cells with drug-specific human leukocyte antigen (HLA) class I restriction and T cell receptors (TCR) repertoire is the key pathogenic for SJS/TEN"
Identifies the HLA class I-restricted, drug-specific cytotoxic T-cell immune synapse as the key pathogenic event, matching this trigger node. Evidence source is OTHER because this is a review article.
Drug-Specific Cytotoxic T-Cell and NK-Cell Activation
amplifier
Drug-specific CD8 T cells and natural killer cells are activated and expand, becoming the effector population that targets keratinocytes — the amplifying step linking antigen recognition to tissue injury.
Downstream
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Cytotoxic Mediator Release and Keratinocyte Death
Activated cytotoxic lymphocytes release mediators that kill keratinocytes.
Show evidence (1 reference)
"Drug-specific CD8 T-cells and natural killer cells are thought to be the major inducers of keratinocyte apoptosis via release of soluble cytotoxic mediators, including Fas ligand, perforin/granzyme, tumor necrosis factor, and granulysin."
Identifies drug-specific CD8 T cells and NK cells as the effector population that drives keratinocyte death, the amplifier captured here. Evidence source is OTHER because this is a review article.
Epidermal Necrolysis and Detachment
effector
Confluent keratinocyte death produces full-thickness epidermal necrosis that separates the epidermis from the dermis, the histopathologic hallmark of SJS/TEN that manifests as widespread skin and mucosal detachment.
Downstream
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Mucocutaneous Failure and Systemic Complications
Loss of the epidermal barrier produces life-threatening systemic consequences.
Show evidence (2 references)
"Total epidermal necrosis separates the epidermis from the dermis."
Describes full-thickness epidermal necrosis with dermo-epidermal separation, the effector lesion of this module. Evidence source is OTHER because this is a review article.
"severe mucocutaneous bullous disorders characterized by widespread skin and mucosal necrosis and detachment, which are most commonly triggered by medications"
Characterizes SJS/TEN as drug-triggered mucocutaneous necrosis and detachment, the clinical expression of this node. Evidence source is OTHER because this is a review article.
Mucocutaneous Failure and Systemic Complications
consequence
Extensive epidermal and mucosal detachment causes failure of the skin barrier, with fluid loss, infection risk, and multi-organ involvement, producing the high mortality of SJS/TEN — the defining consequence of the module.
Show evidence (2 references)
"immunologically mediated cutaneous adverse reaction characterized by mucous membrane and epidermal detachment, with a mortality ranging from 15% to 25%"
Documents the mucocutaneous detachment and high mortality that define the consequence of this module. Evidence source is OTHER because this is a review article.
"life-threatening cutaneous adverse drug reactions that induce widespread epidermal necrosis"
Frames SJS/TEN as life-threatening drug reactions producing widespread epidermal necrosis. Evidence source is OTHER because this is a review article.