Allopurinol-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Complex MONDO:0044739 Pathograph 7 Show in embeddings browser Skin Disease Iatrogenic condition

Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). The reaction is a T-cell-mediated, type IV hypersensitivity strongly gated by the HLA-B*58:01 risk allele: allopurinol and its metabolite oxypurinol are presented in an HLA class I-restricted manner to drug-specific cytotoxic T cells, which kill keratinocytes and produce epidermal necrolysis and detachment. It is the best-characterized pharmacogenomic SCAR and conforms to the conserved drug hypersensitivity (SCAR) mechanism module.

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1
Mappings
5
Pathophys.
5
Phenotypes
7
Pathograph
1
Genes
2
Medical Actions
🔗

Mappings

MONDO
MONDO:0044739 Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome
skos:closeMatch MONDO
MONDO SJS/TEN overlap syndrome captures the cutaneous-reaction spectrum; this entry specializes it to the allopurinol-triggered, HLA-B*58:01-gated form.
⚙

Pathophysiology

5
HLA-B*58:01-restricted allopurinol/oxypurinol presentation
Allopurinol and its active metabolite oxypurinol are presented in an HLA class I-restricted manner to drug-specific T cells; the HLA-B*58:01 allele provides the restricting element, making this the initiating immunological lesion of the conserved SCAR module in its allopurinol-specific form.
CD8-positive cytotoxic T cell CL:0000625 keratinocyte CL:0000312
antigen processing and presentation GO:0019882 ↑ INCREASED
Downstream
Drug-specific cytotoxic T-cell activation HLA-restricted presentation activates drug-specific cytotoxic T cells.
Show evidence (2 references)
PMID:28133001 SUPPORT Other
"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 the SCAR trigger as a type IV hypersensitivity driven by drug, HLA alleles, and T-cell clonotypes, matching the module trigger node this disease conforms to. Evidence source is OTHER because this is a review.
PMID:15743917 SUPPORT Human Clinical
"The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients"
Human case-control data show the HLA-B*58:01 allele in all allopurinol-SCAR patients, identifying the HLA restriction element that gates the trigger.
Drug-specific cytotoxic T-cell activation
Allopurinol/oxypurinol-specific CD8 T cells (and NK cells) are activated and expand, becoming the effector population that targets keratinocytes.
CD8-positive cytotoxic T cell CL:0000625 natural killer cell CL:0000623
T cell activation GO:0042110 ↑ INCREASED
Downstream
Keratinocyte death by cytotoxic mediators Activated cytotoxic lymphocytes release mediators that kill keratinocytes.
Show evidence (1 reference)
PMID:33341195 SUPPORT Other
"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 driving keratinocyte death, matching the module amplifier node. Evidence source is OTHER because this is a review article.
Keratinocyte death by cytotoxic mediators
Activated lymphocytes release granulysin, Fas ligand, and perforin/granzyme, driving keratinocyte apoptosis and necroptosis — the central effector lesion of allopurinol SJS/TEN and the key conformance target of the SCAR module.
keratinocyte CL:0000312
T cell mediated cytotoxicity GO:0001913 ↑ INCREASED apoptotic process GO:0006915 ↑ INCREASED
Downstream
Epidermal necrolysis and detachment Confluent keratinocyte death produces full-thickness epidermal necrosis.
Show evidence (2 references)
PMID:25355273 SUPPORT Other
"With regard to keratinocyte death, several cell death mediators, such as FasL, granulysin and annexin A1, have been proposed as playing a role in SJS/TEN pathogenesis."
Names the cytotoxic mediators (FasL, granulysin) effecting keratinocyte death, matching the module central-effector node. Evidence source is OTHER because this is a review article.
PMID:28133001 SUPPORT Other
"Apoptosis or necroptosis causes keratinocytes to lose their shape and adhesion, and necrosis predominates within a few days."
Specifies apoptosis and necroptosis as the keratinocyte death modalities of SJS/TEN. Evidence source is OTHER because this is a review article.
Epidermal necrolysis and detachment
Confluent keratinocyte death produces full-thickness epidermal necrosis that separates the epidermis from the dermis, manifesting as the skin and mucosal detachment of allopurinol SJS/TEN.
keratinocyte CL:0000312
cell death GO:0008219 ↑ INCREASED
Downstream
Mucocutaneous failure Loss of the epidermal barrier produces systemic consequences.
Show evidence (1 reference)
PMID:28133001 SUPPORT Other
"Total epidermal necrosis separates the epidermis from the dermis."
Describes the full-thickness epidermal necrosis with dermo-epidermal separation that defines TEN, matching the module effector node. Evidence source is OTHER because this is a review article.
Mucocutaneous failure
Extensive epidermal and mucosal detachment causes skin-barrier failure with high morbidity and mortality, the defining consequence of allopurinol SJS/TEN.
keratinocyte CL:0000312
cell death GO:0008219 ↑ INCREASED
Show evidence (1 reference)
PMID:33341195 SUPPORT Other
"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 SJS/TEN. Evidence source is OTHER because this is a review.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Allopurinol-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Cardiovascular 1
Conjunctivitis Conjunctivitis HP:0000509
Show evidence (1 reference)
PMID:37881633 SUPPORT Human Clinical
"conjunctivitis with/without ocular discharge"
Drug-induced SJS/TEN case series reporting conjunctivitis, supporting ocular involvement as a feature.
Head and Neck 1
Oral mucosal ulceration Oral ulcer HP:0000155
Show evidence (1 reference)
PMID:37881633 SUPPORT Human Clinical
"mucosal lesions (15 cases, 88.2%)"
Drug-induced SJS/TEN case series reporting mucosal lesions in the large majority of patients, supporting mucosal/oral involvement as a hallmark.
Integument 2
Skin detachment Skin detachment HP:0032156
Show evidence (1 reference)
PMID:33341195 SUPPORT Other
"immunologically mediated cutaneous adverse reaction characterized by mucous membrane and epidermal detachment, with a mortality ranging from 15% to 25%"
Identifies mucous membrane and epidermal detachment as the defining feature. Evidence source is OTHER because this is a review article.
Abnormal blistering of the skin Abnormal blistering of the skin HP:0008066
Show evidence (1 reference)
PMID:35437717 SUPPORT Other
"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 bullous disorders. Evidence source is OTHER because this is a review article.
Metabolism 1
Fever Fever HP:0001945
Show evidence (1 reference)
PMID:37881633 SUPPORT Human Clinical
"fever (11 cases, 64.7%)"
Drug-induced SJS/TEN case series reporting fever in the majority of patients, supporting fever as a characteristic prodromal feature.
🧬

Genetic Associations

1
HLA-B*58:01 pharmacogenomic susceptibility (HLA-B*58:01 strongly predisposes to allopurinol-induced SCAR (SJS/TEN))
Gene: HLA-B hgnc:4932 relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (2 references)
PMID:15743917 SUPPORT Human Clinical
"The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients"
Human case-control data establish HLA-B*58:01 as a strong genetic risk factor for allopurinol-induced SCAR.
PMID:25047754 SUPPORT Other
"the HLA-B5801 allele and renal impairment are strongly associated with SCARs"
Confirms the HLA-B*58:01 association (and renal impairment as a cofactor) with allopurinol SCAR. Evidence source is OTHER because this is a cost-effectiveness modeling study.
💊

Medical Actions

2
Causative drug withdrawal and supportive care
Action: supportive care MAXO:0000950
Immediate withdrawal of allopurinol and multidisciplinary supportive care (often in an ICU or burn unit) are the cornerstone of management.
Show evidence (1 reference)
PMID:35437717 SUPPORT Other
"immediate withdrawal of causative agents, and critical multidisciplinary supportive care are key management of SJS/TEN"
Identifies causative-drug withdrawal and supportive care as key management of SJS/TEN. Evidence source is OTHER because this is a review article.
HLA-B*58:01 pre-prescription screening
Action: genetic testing MAXO:0000127
Genotyping for HLA-B*58:01 before allopurinol in high-risk populations to avoid the drug in carriers and prevent SCAR.
Show evidence (1 reference)
PMID:25047754 SUPPORT Other
"Recent American College of Rheumatology guidelines recommend that, prior to treatment with allopurinol, the HLA-B5801 genotype of gout patients at high risk for SCARs, including Korean patients with chronic renal insufficiency, should be determined."
Supports HLA-B*58:01 pre-prescription genotyping as a guideline-recommended preventive strategy. Evidence source is OTHER because this is a cost-effectiveness modeling study.
🌍

Environmental Factors

1
Allopurinol exposure
Therapeutic exposure to allopurinol (for gout/hyperuricemia), especially in HLA-B*58:01 carriers and in renal impairment, is the precipitating exposure.
Show evidence (1 reference)
PMID:15743917 SUPPORT Human Clinical
"Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis."
Establishes allopurinol as a frequent cause of SCAR including SJS/TEN, the exposure that precipitates this disease.
{ }

Source YAML

click to show 
name: Allopurinol-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
creation_date: "2026-06-24T00:00:00Z"
category: Complex
categories:
- Treatment-Related Disorder
- Cutaneous Toxicity
- Adverse Drug Reaction
synonyms:
- allopurinol-induced SJS/TEN
- allopurinol-induced severe cutaneous adverse reaction
- allopurinol SCAR
description: >-
  Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs),
  including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). The
  reaction is a T-cell-mediated, type IV hypersensitivity strongly gated by the
  HLA-B*58:01 risk allele: allopurinol and its metabolite oxypurinol are presented
  in an HLA class I-restricted manner to drug-specific cytotoxic T cells, which
  kill keratinocytes and produce epidermal necrolysis and detachment. It is the
  best-characterized pharmacogenomic SCAR and conforms to the conserved drug
  hypersensitivity (SCAR) mechanism module.
parents:
- Skin Disease
- Iatrogenic condition
disease_term:
  preferred_term: allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis
  term:
    id: MONDO:0044739
    label: Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0044739
      label: Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      MONDO SJS/TEN overlap syndrome captures the cutaneous-reaction spectrum;
      this entry specializes it to the allopurinol-triggered, HLA-B*58:01-gated
      form.
environmental:
- name: Allopurinol exposure
  description: >-
    Therapeutic exposure to allopurinol (for gout/hyperuricemia), especially in
    HLA-B*58:01 carriers and in renal impairment, is the precipitating exposure.
  evidence:
  - reference: PMID:15743917
    reference_title: "HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Allopurinol, a commonly prescribed medication for gout and hyperuricemia,
      is a frequent cause of severe cutaneous adverse reactions (SCAR), which
      include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and
      toxic epidermal necrolysis.
    explanation: >-
      Establishes allopurinol as a frequent cause of SCAR including SJS/TEN, the
      exposure that precipitates this disease.
pathophysiology:
- name: HLA-B*58:01-restricted allopurinol/oxypurinol presentation
  conforms_to: "drug_hypersensitivity_scar#HLA-Restricted Drug Presentation to Drug-Specific T Cells"
  description: >-
    Allopurinol and its active metabolite oxypurinol are presented in an HLA class
    I-restricted manner to drug-specific T cells; the HLA-B*58:01 allele provides
    the restricting element, making this the initiating immunological lesion of
    the conserved SCAR module in its allopurinol-specific form.
  role: trigger
  cell_types:
  - preferred_term: CD8-positive cytotoxic T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: antigen processing and presentation
    term:
      id: GO:0019882
      label: antigen processing and presentation
    modifier: INCREASED
  evidence:
  - reference: PMID:28133001
    reference_title: "A Review of the Pathogenesis of Toxic Epidermal Necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      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.
    explanation: >-
      Frames the SCAR trigger as a type IV hypersensitivity driven by drug, HLA
      alleles, and T-cell clonotypes, matching the module trigger node this
      disease conforms to. Evidence source is OTHER because this is a review.
  - reference: PMID:15743917
    reference_title: "HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The HLA-B*5801 allele was present in all (100%) 51 patients with
      allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients
    explanation: >-
      Human case-control data show the HLA-B*58:01 allele in all allopurinol-SCAR
      patients, identifying the HLA restriction element that gates the trigger.
  downstream:
  - target: Drug-specific cytotoxic T-cell activation
    description: >-
      HLA-restricted presentation activates drug-specific cytotoxic T cells.
- name: Drug-specific cytotoxic T-cell activation
  conforms_to: "drug_hypersensitivity_scar#Drug-Specific Cytotoxic T-Cell and NK-Cell Activation"
  description: >-
    Allopurinol/oxypurinol-specific CD8 T cells (and NK cells) are activated and
    expand, becoming the effector population that targets keratinocytes.
  role: amplifier
  cell_types:
  - preferred_term: CD8-positive cytotoxic T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  - preferred_term: natural killer cell
    term:
      id: CL:0000623
      label: natural killer cell
  biological_processes:
  - preferred_term: T cell activation
    term:
      id: GO:0042110
      label: T cell activation
    modifier: INCREASED
  evidence:
  - reference: PMID:33341195
    reference_title: "Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      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.
    explanation: >-
      Identifies drug-specific CD8 T cells and NK cells as the effector population
      driving keratinocyte death, matching the module amplifier node. Evidence
      source is OTHER because this is a review article.
  downstream:
  - target: Keratinocyte death by cytotoxic mediators
    description: >-
      Activated cytotoxic lymphocytes release mediators that kill keratinocytes.
- name: Keratinocyte death by cytotoxic mediators
  conforms_to: "drug_hypersensitivity_scar#Cytotoxic Mediator Release and Keratinocyte Death"
  description: >-
    Activated lymphocytes release granulysin, Fas ligand, and perforin/granzyme,
    driving keratinocyte apoptosis and necroptosis — the central effector lesion
    of allopurinol SJS/TEN and the key conformance target of the SCAR module.
  role: central_effector
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: T cell mediated cytotoxicity
    term:
      id: GO:0001913
      label: T cell mediated cytotoxicity
    modifier: INCREASED
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
    modifier: INCREASED
  evidence:
  - reference: PMID:25355273
    reference_title: "Immunological response in Stevens-Johnson syndrome and toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      With regard to keratinocyte death, several cell death mediators, such as
      FasL, granulysin and annexin A1, have been proposed as playing a role in
      SJS/TEN pathogenesis.
    explanation: >-
      Names the cytotoxic mediators (FasL, granulysin) effecting keratinocyte
      death, matching the module central-effector node. Evidence source is OTHER
      because this is a review article.
  - reference: PMID:28133001
    reference_title: "A Review of the Pathogenesis of Toxic Epidermal Necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Apoptosis or necroptosis causes keratinocytes to lose their shape and
      adhesion, and necrosis predominates within a few days.
    explanation: >-
      Specifies apoptosis and necroptosis as the keratinocyte death modalities of
      SJS/TEN. Evidence source is OTHER because this is a review article.
  downstream:
  - target: Epidermal necrolysis and detachment
    description: >-
      Confluent keratinocyte death produces full-thickness epidermal necrosis.
- name: Epidermal necrolysis and detachment
  conforms_to: "drug_hypersensitivity_scar#Epidermal Necrolysis and Detachment"
  description: >-
    Confluent keratinocyte death produces full-thickness epidermal necrosis that
    separates the epidermis from the dermis, manifesting as the skin and mucosal
    detachment of allopurinol SJS/TEN.
  role: effector
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: cell death
    term:
      id: GO:0008219
      label: cell death
    modifier: INCREASED
  evidence:
  - reference: PMID:28133001
    reference_title: "A Review of the Pathogenesis of Toxic Epidermal Necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Total epidermal necrosis separates the epidermis from the dermis.
    explanation: >-
      Describes the full-thickness epidermal necrosis with dermo-epidermal
      separation that defines TEN, matching the module effector node. Evidence
      source is OTHER because this is a review article.
  downstream:
  - target: Mucocutaneous failure
    description: >-
      Loss of the epidermal barrier produces systemic consequences.
- name: Mucocutaneous failure
  conforms_to: "drug_hypersensitivity_scar#Mucocutaneous Failure and Systemic Complications"
  description: >-
    Extensive epidermal and mucosal detachment causes skin-barrier failure with
    high morbidity and mortality, the defining consequence of allopurinol SJS/TEN.
  role: consequence
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: cell death
    term:
      id: GO:0008219
      label: cell death
    modifier: INCREASED
  evidence:
  - reference: PMID:33341195
    reference_title: "Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      immunologically mediated cutaneous adverse reaction characterized by mucous
      membrane and epidermal detachment, with a mortality ranging from 15% to 25%
    explanation: >-
      Documents the mucocutaneous detachment and high mortality that define the
      consequence of SJS/TEN. Evidence source is OTHER because this is a review.
genetic:
- name: HLA-B*58:01 pharmacogenomic susceptibility
  gene_term:
    preferred_term: HLA-B
    term:
      id: hgnc:4932
      label: HLA-B
  association: HLA-B*58:01 strongly predisposes to allopurinol-induced SCAR (SJS/TEN)
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  notes: >-
    HLA-B*58:01 is a clinically actionable pharmacogenomic risk allele; American
    College of Rheumatology guidance recommends HLA-B*58:01 genotyping before
    allopurinol in high-risk groups (e.g. patients of Han Chinese, Korean, and
    Thai ancestry, and those with chronic kidney disease).
  variants:
  - name: HLA-B*58:01
    description: >-
      Class I HLA allele present in essentially all allopurinol-SCAR patients in
      the index Han Chinese case-control study; the restricting element for
      drug-specific T-cell recognition.
  evidence:
  - reference: PMID:15743917
    reference_title: "HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The HLA-B*5801 allele was present in all (100%) 51 patients with
      allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients
    explanation: >-
      Human case-control data establish HLA-B*58:01 as a strong genetic risk
      factor for allopurinol-induced SCAR.
  - reference: PMID:25047754
    reference_title: "Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the HLA-B5801 allele and renal impairment are strongly associated with
      SCARs
    explanation: >-
      Confirms the HLA-B*58:01 association (and renal impairment as a cofactor)
      with allopurinol SCAR. Evidence source is OTHER because this is a
      cost-effectiveness modeling study.
phenotypes:
- name: Skin detachment
  description: >-
    Widespread epidermal and mucosal detachment, the defining feature of SJS/TEN.
  phenotype_term:
    preferred_term: Skin detachment
    term:
      id: HP:0032156
      label: Skin detachment
  evidence:
  - reference: PMID:33341195
    reference_title: "Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      immunologically mediated cutaneous adverse reaction characterized by mucous
      membrane and epidermal detachment, with a mortality ranging from 15% to 25%
    explanation: >-
      Identifies mucous membrane and epidermal detachment as the defining feature.
      Evidence source is OTHER because this is a review article.
- name: Abnormal blistering of the skin
  description: >-
    Mucocutaneous bullae preceding epidermal detachment.
  phenotype_term:
    preferred_term: Mucocutaneous blistering
    term:
      id: HP:0008066
      label: Abnormal blistering of the skin
  evidence:
  - reference: PMID:35437717
    reference_title: "Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Era of Systems Medicine."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      severe mucocutaneous bullous disorders characterized by widespread skin and
      mucosal necrosis and detachment, which are most commonly triggered by
      medications
    explanation: >-
      Characterizes SJS/TEN as drug-triggered mucocutaneous bullous disorders.
      Evidence source is OTHER because this is a review article.
- name: Oral mucosal ulceration
  description: >-
    Painful oral/mucosal erosions; mucosal involvement is a diagnostic hallmark of
    SJS/TEN and is present in the large majority of patients.
  phenotype_term:
    preferred_term: Oral mucosal ulceration
    term:
      id: HP:0000155
      label: Oral ulcer
  evidence:
  - reference: PMID:37881633
    reference_title: "Analysis of clinical features of oxcarbazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      mucosal lesions (15 cases, 88.2%)
    explanation: >-
      Drug-induced SJS/TEN case series reporting mucosal lesions in the large
      majority of patients, supporting mucosal/oral involvement as a hallmark.
- name: Conjunctivitis
  description: >-
    Ocular surface inflammation; ocular involvement is common in SJS/TEN and can
    cause long-term sequelae.
  phenotype_term:
    preferred_term: Conjunctivitis
    term:
      id: HP:0000509
      label: Conjunctivitis
  evidence:
  - reference: PMID:37881633
    reference_title: "Analysis of clinical features of oxcarbazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      conjunctivitis with/without ocular discharge
    explanation: >-
      Drug-induced SJS/TEN case series reporting conjunctivitis, supporting ocular
      involvement as a feature.
- name: Fever
  description: >-
    Prodromal fever characteristically precedes and accompanies the cutaneous
    eruption.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:37881633
    reference_title: "Analysis of clinical features of oxcarbazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      fever (11 cases, 64.7%)
    explanation: >-
      Drug-induced SJS/TEN case series reporting fever in the majority of
      patients, supporting fever as a characteristic prodromal feature.
treatments:
- name: Causative drug withdrawal and supportive care
  description: >-
    Immediate withdrawal of allopurinol and multidisciplinary supportive care
    (often in an ICU or burn unit) are the cornerstone of management.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:35437717
    reference_title: "Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Era of Systems Medicine."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      immediate withdrawal of causative agents, and critical multidisciplinary
      supportive care are key management of SJS/TEN
    explanation: >-
      Identifies causative-drug withdrawal and supportive care as key management
      of SJS/TEN. Evidence source is OTHER because this is a review article.
- name: HLA-B*58:01 pre-prescription screening
  description: >-
    Genotyping for HLA-B*58:01 before allopurinol in high-risk populations to
    avoid the drug in carriers and prevent SCAR.
  treatment_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: PMID:25047754
    reference_title: "Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Recent American College of Rheumatology guidelines recommend that, prior to
      treatment with allopurinol, the HLA-B5801 genotype of gout patients at high
      risk for SCARs, including Korean patients with chronic renal insufficiency,
      should be determined.
    explanation: >-
      Supports HLA-B*58:01 pre-prescription genotyping as a guideline-recommended
      preventive strategy. Evidence source is OTHER because this is a
      cost-effectiveness modeling study.