IgG4-Related Sclerosing Cholangitis

Autoimmune MONDO:0018645 Pathograph 4 Autoimmune Disease Liver Disease

Organ-specific biliary involvement of IgG4-related disease, characterized by inflammatory and fibrostenotic lesions of the intrahepatic and/or extrahepatic bile ducts. The disorder frequently co-occurs with type 1 autoimmune pancreatitis and can present with jaundice, cholestatic liver tests, or bile-duct strictures that mimic primary sclerosing cholangitis or cholangiocarcinoma. Diagnosis requires integration of imaging, serology, histopathology, other-organ involvement, and response to immunosuppressive therapy after malignancy has been excluded.

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3
Pathophys.
2
Histopath.
7
Phenotypes
4
Pathograph
1
Genes
4
Treatments
2
Differentials
14
References
1
Deep Research
⚙

Pathophysiology

3
B Cell and Plasmablast Activation
Upstream adaptive immune activation in IgG4-related hepatobiliary disease includes B-cell and plasmablast expansion alongside T-cell immune features, providing a mechanistic rationale for B-cell depletion therapy in relapsing pancreaticobiliary IgG4-related disease.
B cell link plasmablast link regulatory T cell link
B cell activation link humoral immune response link
Downstream
IgG4-Rich Lymphoplasmacytic Bile Duct Inflammation
Show evidence (1 reference)
PMID:27625195 SUPPORT Human Clinical
"Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system."
This review supports upstream B-cell/plasmablast and T-cell immune features in IgG4-related hepatobiliary disease.
IgG4-Rich Lymphoplasmacytic Bile Duct Inflammation
IgG4-positive plasma cells and lymphocytes infiltrate the bile duct wall, producing an immune-mediated cholangitis focused on the biliary tree rather than a generic systemic IgG4-related disease entry.
Plasma cell link CD4-positive, alpha-beta T cell link
Immune response link Inflammatory response link
Downstream
Bile Duct Fibrostenosis
Show evidence (2 references)
PMID:30575336 SUPPORT Human Clinical
"IgG4-related sclerosing cholangitis (IgG4-SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4-related disease."
The guideline defines IgG4-SC as a distinct bile-duct manifestation of IgG4-related disease, supporting the organ-specific scope of this entry.
PMID:26593290 SUPPORT Human Clinical
"Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the multisystem IgG4-related disease."
This review independently supports the biliary manifestation framing.
Bile Duct Fibrostenosis
Fibroinflammatory remodeling around affected bile ducts narrows the duct lumen and causes cholestasis, biliary obstruction, and downstream liver injury.
Fibroblast link
Extracellular matrix organization link
Show evidence (2 references)
PMID:30205418 SUPPORT Human Clinical
"Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis and currently includes three categories: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing cholangitis..."
The guideline places IgG4-SC within fibrostenotic bile-duct disease and supports bile-duct stenosis and fibrosis as core pathobiology.
PMID:27625195 SUPPORT Human Clinical
"These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies."
This review supports biliary strictures as a core manifestation of IgG4-related hepatobiliary disease.
✶

Histopathology

2
Transmural lymphoplasmacytic inflammation and fibrosis of bile ducts
Affected large bile ducts show transmural lymphoplasmacytic inflammation and fibrosis that thickens the duct wall; IgG4 immunostaining is supportive but not sufficient alone.
Show evidence (1 reference)
PMID:30575336 SUPPORT Human Clinical
"In intrahepatic and extrahepatic large bile ducts, transmural marked lymphoplasmacytic infiltration and fibrosis are observed, which give rise to bile duct wall thickening."
This guideline statement directly supports the microscopic bile-duct inflammatory and fibrotic pattern.
Storiform fibrosis and obliterative phlebitis
Storiform fibrosis and obliterative phlebitis are diagnostically important IgG4-RD-type tissue features when found in bile duct tissue.
Show evidence (1 reference)
PMID:30575336 SUPPORT Human Clinical
"Notably, storiform fibrosis and obliterative phlebitis are important histologic findings for diagnosing IgG4-SC."
Supports these two findings as diagnostic histopathologic features.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for IgG4-Related Sclerosing Cholangitis 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

7
Digestive 4
Sclerosing Cholangitis Sclerosing cholangitis (HP:0030991)
Show evidence (1 reference)
PMID:26593290 SUPPORT Human Clinical
"IgG4-SC presents with biliary strictures and/or masses that can bear a striking similarity to other malignant and inflammatory diseases."
The abstract supports sclerosing cholangitis with biliary strictures as the central clinical phenotype.
Jaundice Jaundice (HP:0000952)
Show evidence (1 reference)
PMID:40191403 SUPPORT Human Clinical
"Patients often present with jaundice and weight loss, mimicking hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer."
This directly supports jaundice as a common presentation of IgG4-related cholangitis.
Cholestasis Cholestasis (HP:0001396)
Show evidence (1 reference)
PMID:30205418 SUPPORT Human Clinical
"SC categories share similar clinical features, such as cholestasis."
Supports cholestasis as a shared clinical feature of sclerosing cholangitis categories, including IgG4-SC.
Autoimmune Pancreatitis Pancreatitis (HP:0001733)
Type 1 autoimmune pancreatitis commonly co-occurs and can help distinguish IgG4-SC from PSC or cholangiocarcinoma.
Show evidence (1 reference)
PMID:30575336 SUPPORT Human Clinical
"IgG4-related sclerosing cholangitis (IgG4-SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4-related disease."
The guideline supports frequent association with autoimmune pancreatitis.
Integument 1
Pruritus Pruritus (HP:0000989)
Show evidence (1 reference)
PMID:30205418 SUPPORT Human Clinical
"Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes."
This review supports pruritus as a cholestatic symptom relevant to sclerosing cholangitis, including IgG4-SC.
Constitutional 1
Abdominal Pain Abdominal pain (HP:0002027)
Growth 1
Weight Loss Weight loss (HP:0001824)
Show evidence (1 reference)
PMID:40191403 SUPPORT Human Clinical
"Patients often present with jaundice and weight loss, mimicking hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer."
This directly supports weight loss as a presenting symptom.
🧬

Genetic Associations

1
HLA-region methylation quantitative trait loci (Susceptibility Factor)
Show evidence (1 reference)
PMID:39819503 SUPPORT Computational
"meQTL analyses to identify genetic determinants of methylation revealed a strong human leucocyte antigen (HLA) signal in both PSC and IgG4-SC (HLA-DQB2, HLA-DPA1, HLA-F and HLA-DRA)."
This human-sample omics study uses methylation/genotyping data and computational meQTL analysis to support HLA-region susceptibility architecture without implying Mendelian inheritance.
💊

Treatments

4
Glucocorticoids
Action: glucocorticoid therapy Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Agent: corticosteroid ↗
First-line anti-inflammatory therapy for active IgG4-related sclerosing cholangitis after diagnosis is secure and malignancy has been excluded.
Show evidence (2 references)
PMID:26593290 SUPPORT Human Clinical
"Corticosteroids are the mainstay of treatment with good clinical, biochemical, and radiological responses."
Directly supports corticosteroids as first-line therapy.
PMID:40191403 SUPPORT Human Clinical
"IRC responds well to corticosteroid therapy, though relapses are common, necessitating long-term immunosuppressive treatment in many cases."
Supports both treatment response and the need to monitor for relapse.
Rituximab
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: rituximab ↗
B-cell depletion therapy used for relapsing, steroid-dependent, or refractory pancreaticobiliary IgG4-related disease, including IgG4-SC.
Mechanism Target:
INHIBITS B Cell and Plasmablast Activation — Rituximab depletes CD20-positive B-cell lineage populations upstream of IgG4-rich tissue inflammation and is used to prolong remission in pancreaticobiliary IgG4-related disease.
Show evidence (2 references)
PMID:29526692 SUPPORT Human Clinical
"Thirty-seven patients (86%) were in steroid-free remission 6 months after rituximab initiation."
Supports rituximab efficacy in pancreaticobiliary IgG4-related disease.
PMID:29526692 SUPPORT Human Clinical
"A higher proportion of patients in group 1 had disease relapse (3-year event rate, 45%) than in group 2 (3-year event rate, 11%) (P = .034)."
Supports maintenance rituximab as relapse-reducing in a pancreaticobiliary IgG4-RD cohort.
Azathioprine
Action: Pharmacotherapy NCIT:C15986
Agent: azathioprine ↗
Steroid-sparing immunomodulator used as a remission-induction or maintenance option when long-term immunosuppression is needed.
Show evidence (1 reference)
PMID:40191403 SUPPORT Human Clinical
"Steroid-sparing agents for remission induction and maintenance therapy comprise immunomodulators, such as azathioprine, as well as B-cell depletion therapies, such as rituximab."
This review supports azathioprine as a steroid-sparing immunomodulator option in IgG4-related cholangitis.
Biliary Drainage or Stenting
Action: therapeutic procedure Ontology label: Therapeutic Procedure NCIT:C49236
Endoscopic decompression is used selectively for clinically significant obstructive jaundice, cholangitis, or dominant biliary strictures; stents should be removed promptly when strictures improve after corticosteroids.
Show evidence (2 references)
PMID:32353060 SUPPORT Human Clinical
"Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation."
Supports real-world use of endoscopic biliary drainage before corticosteroid initiation in a subset of IgG4-SC patients.
PMID:32353060 SUPPORT Human Clinical
"Obstructive jaundice can be treated safely with CS alone in patients without infection."
Supports selective, rather than automatic, stenting when obstructive jaundice is present without infection.
🔬

Biochemical Markers

2
Serum IgG4 (Elevated)
Context: Serum IgG4 elevation supports the diagnosis but is not specific and cannot exclude PSC or cholangiocarcinoma by itself.
Show evidence (2 references)
PMID:30575336 SUPPORT Human Clinical
"An elevation of serum IgG4 levels is seen in most cases of IgG4-SC, so it is useful for the diagnosis of IgG4-SC."
Supports serum IgG4 as a useful diagnostic biochemical feature.
PMID:30575336 SUPPORT Human Clinical
"However, an elevation of serum IgG4 levels is not specific for the diagnosis of IgG4-SC."
Captures the limitation that IgG4 elevation is supportive but not independently diagnostic.
Alkaline Phosphatase (Elevated)
Context: Cholestatic liver enzyme pattern due to bile duct obstruction.
Show evidence (1 reference)
PMID:30205418 SUPPORT Human Clinical
"Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes."
Supports cholestatic enzyme elevation; alkaline phosphatase is the clinically emphasized cholestatic enzyme in this entry.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from IgG4-Related Sclerosing Cholangitis:

Primary Sclerosing Cholangitis MONDO:0013433
Overlapping Features PSC can produce similar multifocal bile-duct strictures and cholestatic symptoms but is usually not steroid-responsive and has different comorbidity and outcome patterns.
Distinguishing Features
  • IgG4-SC often co-occurs with autoimmune pancreatitis or other IgG4-related organ disease.
  • PSC is strongly associated with inflammatory bowel disease and does not respond to steroid therapy.
Show evidence (1 reference)
PMID:30205418 SUPPORT Human Clinical
"Although the presentation of IgG4-SC and PSC are similar, the comorbidities, treatment response, and outcomes differ significantly, and therefore, it is strongly advisable to be familiar with these two diseases to make a correct diagnosis."
Supports PSC as a key mimic and highlights distinguishing clinical dimensions.
Cholangiocarcinoma MONDO:0019087
Overlapping Features Cholangiocarcinoma can mimic focal or hilar IgG4-SC strictures and must be excluded before steroid-response is used as diagnostic support.
Distinguishing Features
  • Tissue sampling, cytology, imaging, and repeat evaluation are needed when malignancy remains possible.
  • Steroid trials should be avoided when neoplasia has not been reasonably excluded.
Show evidence (2 references)
PMID:30575336 SUPPORT Human Clinical
"Cholangiographic findings of IgG4-SC involving the hilar and/or intrahepatic bile ducts are similar to those of hilar cholangiocarcinoma or primary sclerosing cholangitis (PSC)."
Supports cholangiocarcinoma as a central imaging mimic.
PMID:30575336 SUPPORT Human Clinical
"If IgG4-SC cannot be clinically ruled out, a patient must not be treated with facile steroid therapy but should be referred to a specialized medical facility."
Supports caution with empiric steroid trials during the differential diagnosis of malignant biliary disease.
{ }

Source YAML

click to show 
name: IgG4-Related Sclerosing Cholangitis
creation_date: "2026-05-07T02:02:26Z"
updated_date: "2026-05-07T02:57:39Z"
category: Autoimmune
parents:
- Autoimmune Disease
- Liver Disease
synonyms:
- IgG4-related cholangitis
- IgG4-associated sclerosing cholangitis
disease_term:
  preferred_term: IgG4-related sclerosing cholangitis
  term:
    id: MONDO:0018645
    label: IgG4-related sclerosing cholangitis
references:
- reference: DOI:10.1002/jhbp.596
  title: Clinical practice guidelines for IgG4-related sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1002/jhbp.70056
  title: Multicenter validation study of the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020 in Japan
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1007/s00535-020-01714-7
  title: "The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience"
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1016/j.cgh.2018.02.049
  title: Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin G4-related disease
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1016/j.cld.2015.08.004
  title: New thoughts on immunoglobulin G4-related sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1038/nrgastro.2016.132
  title: "IgG4-related hepatobiliary disease: an overview"
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1053/j.gastro.2015.01.041
  title: Association between HLA haplotypes and increased serum levels of IgG4 in patients with primary sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1055/a-2588-3875
  title: IgG4-related cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1093/gastro/goaf032
  title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance"
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1136/flgastro-2018-101001
  title: Diagnosis and management of IgG4-related disease
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1186/s13148-024-01803-x
  title: Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.1371/journal.pone.0232089
  title: Management of biliary stricture in patients with IgG4-related sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.3389/fmed.2026.1732637
  title: "IgG4-related sclerosing cholangitis: navigating diagnostic dilemmas and the challenge of relapse"
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
- reference: DOI:10.5009/gnl18085
  title: IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
  found_in:
  - IgG4-Related_Sclerosing_Cholangitis-deep-research-falcon.md
  findings: []
description: >-
  Organ-specific biliary involvement of IgG4-related disease, characterized by
  inflammatory and fibrostenotic lesions of the intrahepatic and/or
  extrahepatic bile ducts. The disorder frequently co-occurs with type 1
  autoimmune pancreatitis and can present with jaundice, cholestatic liver
  tests, or bile-duct strictures that mimic primary sclerosing cholangitis or
  cholangiocarcinoma. Diagnosis requires integration of imaging, serology,
  histopathology, other-organ involvement, and response to immunosuppressive
  therapy after malignancy has been excluded.
pathophysiology:
- name: B Cell and Plasmablast Activation
  description: >-
    Upstream adaptive immune activation in IgG4-related hepatobiliary disease
    includes B-cell and plasmablast expansion alongside T-cell immune features,
    providing a mechanistic rationale for B-cell depletion therapy in relapsing
    pancreaticobiliary IgG4-related disease.
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  - preferred_term: plasmablast
    term:
      id: CL:0000980
      label: plasmablast
  - preferred_term: regulatory T cell
    term:
      id: CL:0000815
      label: regulatory T cell
  biological_processes:
  - preferred_term: B cell activation
    term:
      id: GO:0042113
      label: B cell activation
  - preferred_term: humoral immune response
    term:
      id: GO:0006959
      label: humoral immune response
  downstream:
  - target: IgG4-Rich Lymphoplasmacytic Bile Duct Inflammation
  evidence:
  - reference: PMID:27625195
    reference_title: "IgG4-related hepatobiliary disease: an overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Insights into the genetic and immunological features of the disease have
      increased over the past decade, with an emphasis on HLAs, T cells,
      circulating memory B cells and plasmablasts, chemokine-mediated
      trafficking, as well as the role of the innate immune system.
    explanation: >-
      This review supports upstream B-cell/plasmablast and T-cell immune
      features in IgG4-related hepatobiliary disease.
- name: IgG4-Rich Lymphoplasmacytic Bile Duct Inflammation
  description: >-
    IgG4-positive plasma cells and lymphocytes infiltrate the bile duct wall,
    producing an immune-mediated cholangitis focused on the biliary tree rather
    than a generic systemic IgG4-related disease entry.
  cell_types:
  - preferred_term: Plasma cell
    term:
      id: CL:0000786
      label: plasma cell
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: Immune response
    term:
      id: GO:0006955
      label: immune response
  - preferred_term: Inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Bile Duct Fibrostenosis
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      IgG4-related sclerosing cholangitis (IgG4-SC) is a distinct type of
      cholangitis frequently associated with autoimmune pancreatitis and
      currently recognized as a biliary manifestation of IgG4-related disease.
    explanation: >-
      The guideline defines IgG4-SC as a distinct bile-duct manifestation of
      IgG4-related disease, supporting the organ-specific scope of this entry.
  - reference: PMID:26593290
    reference_title: New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is the
      biliary manifestation of the multisystem IgG4-related disease.
    explanation: >-
      This review independently supports the biliary manifestation framing.
- name: Bile Duct Fibrostenosis
  description: >-
    Fibroinflammatory remodeling around affected bile ducts narrows the duct
    lumen and causes cholestasis, biliary obstruction, and downstream liver
    injury.
  cell_types:
  - preferred_term: Fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: Extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:30205418
    reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sclerosing cholangitis (SC) is defined as a condition with progressive
      stenosis and destruction of the bile ducts due to diffuse inflammation
      and fibrosis and currently includes three categories: primary sclerosing
      cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing
      cholangitis (IgG4-SC).
    explanation: >-
      The guideline places IgG4-SC within fibrostenotic bile-duct disease and
      supports bile-duct stenosis and fibrosis as core pathobiology.
  - reference: PMID:27625195
    reference_title: "IgG4-related hepatobiliary disease: an overview."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      These diseases can present with biliary strictures and/or mass lesions,
      making them difficult to differentiate from primary sclerosing
      cholangitis (PSC) or other hepatobiliary malignancies.
    explanation: >-
      This review supports biliary strictures as a core manifestation of
      IgG4-related hepatobiliary disease.
progression:
  - phase: Chronic relapsing fibroinflammatory disease
    notes: >-
      Disease often improves with corticosteroids but relapse is common and
      fixed fibrotic strictures can require long-term surveillance or
      endoscopic management.
    evidence:
    - reference: PMID:40191403
      reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        IRC responds well to corticosteroid therapy, though relapses are common,
        necessitating long-term immunosuppressive treatment in many cases.
      explanation: >-
        This recent review supports a steroid-responsive but relapsing clinical
        course.
phenotypes:
- category: Hepatobiliary
  name: Sclerosing Cholangitis
  diagnostic: true
  phenotype_term:
    preferred_term: Sclerosing cholangitis
    term:
      id: HP:0030991
      label: Sclerosing cholangitis
  evidence:
  - reference: PMID:26593290
    reference_title: New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      IgG4-SC presents with biliary strictures and/or masses that can bear a
      striking similarity to other malignant and inflammatory diseases.
    explanation: >-
      The abstract supports sclerosing cholangitis with biliary strictures as
      the central clinical phenotype.
- category: Hepatobiliary
  name: Jaundice
  phenotype_term:
    preferred_term: Jaundice
    term:
      id: HP:0000952
      label: Jaundice
  evidence:
  - reference: PMID:40191403
    reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients often present with jaundice and weight loss, mimicking
      hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing
      cholangitis, and pancreatic cancer.
    explanation: >-
      This directly supports jaundice as a common presentation of
      IgG4-related cholangitis.
- category: Constitutional
  name: Weight Loss
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: PMID:40191403
    reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients often present with jaundice and weight loss, mimicking
      hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing
      cholangitis, and pancreatic cancer.
    explanation: >-
      This directly supports weight loss as a presenting symptom.
- category: Dermatological
  name: Pruritus
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: PMID:30205418
    reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with SC present with cholestatic symptoms, including jaundice and
      pruritus, and blood tests reveal elevation of cholestatic enzymes.
    explanation: >-
      This review supports pruritus as a cholestatic symptom relevant to
      sclerosing cholangitis, including IgG4-SC.
- category: Gastrointestinal
  name: Abdominal Pain
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
- category: Hepatobiliary
  name: Cholestasis
  phenotype_term:
    preferred_term: Cholestasis
    term:
      id: HP:0001396
      label: Cholestasis
  evidence:
  - reference: PMID:30205418
    reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SC categories share similar clinical features, such as cholestasis.
    explanation: >-
      Supports cholestasis as a shared clinical feature of sclerosing
      cholangitis categories, including IgG4-SC.
- category: Gastrointestinal
  name: Autoimmune Pancreatitis
  notes: >-
    Type 1 autoimmune pancreatitis commonly co-occurs and can help distinguish
    IgG4-SC from PSC or cholangiocarcinoma.
  phenotype_term:
    preferred_term: Pancreatitis
    term:
      id: HP:0001733
      label: Pancreatitis
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      IgG4-related sclerosing cholangitis (IgG4-SC) is a distinct type of
      cholangitis frequently associated with autoimmune pancreatitis and
      currently recognized as a biliary manifestation of IgG4-related disease.
    explanation: >-
      The guideline supports frequent association with autoimmune pancreatitis.
histopathology:
- name: Transmural lymphoplasmacytic inflammation and fibrosis of bile ducts
  diagnostic: true
  description: >-
    Affected large bile ducts show transmural lymphoplasmacytic inflammation
    and fibrosis that thickens the duct wall; IgG4 immunostaining is supportive
    but not sufficient alone.
  finding_term:
    preferred_term: transmural lymphoplasmacytic bile-duct inflammation and fibrosis
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In intrahepatic and extrahepatic large bile ducts, transmural marked
      lymphoplasmacytic infiltration and fibrosis are observed, which give rise
      to bile duct wall thickening.
    explanation: >-
      This guideline statement directly supports the microscopic bile-duct
      inflammatory and fibrotic pattern.
- name: Storiform fibrosis and obliterative phlebitis
  diagnostic: true
  description: >-
    Storiform fibrosis and obliterative phlebitis are diagnostically important
    IgG4-RD-type tissue features when found in bile duct tissue.
  finding_term:
    preferred_term: storiform fibrosis and obliterative phlebitis
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Notably, storiform fibrosis and obliterative phlebitis are important
      histologic findings for diagnosing IgG4-SC.
    explanation: >-
      Supports these two findings as diagnostic histopathologic features.
biochemical:
- name: Serum IgG4
  presence: Elevated
  context: >-
    Serum IgG4 elevation supports the diagnosis but is not specific and cannot
    exclude PSC or cholangiocarcinoma by itself.
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An elevation of serum IgG4 levels is seen in most cases of IgG4-SC, so it
      is useful for the diagnosis of IgG4-SC.
    explanation: >-
      Supports serum IgG4 as a useful diagnostic biochemical feature.
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      However, an elevation of serum IgG4 levels is not specific for the
      diagnosis of IgG4-SC.
    explanation: >-
      Captures the limitation that IgG4 elevation is supportive but not
      independently diagnostic.
- name: Alkaline Phosphatase
  presence: Elevated
  context: Cholestatic liver enzyme pattern due to bile duct obstruction.
  evidence:
  - reference: PMID:30205418
    reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with SC present with cholestatic symptoms, including jaundice and
      pruritus, and blood tests reveal elevation of cholestatic enzymes.
    explanation: >-
      Supports cholestatic enzyme elevation; alkaline phosphatase is the
      clinically emphasized cholestatic enzyme in this entry.
genetic:
- name: HLA-region methylation quantitative trait loci
  association: Susceptibility Factor
  relationship_type: SUSCEPTIBILITY
  notes: >-
    No monogenic cause is established. Recent whole-blood methylation and
    genotyping data implicate HLA-region genetic variation in shaping the
    methylome in IgG4-SC.
  evidence:
  - reference: PMID:39819503
    reference_title: Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      meQTL analyses to identify genetic determinants of methylation revealed a
      strong human leucocyte antigen (HLA) signal in both PSC and IgG4-SC
      (HLA-DQB2, HLA-DPA1, HLA-F and HLA-DRA).
    explanation: >-
      This human-sample omics study uses methylation/genotyping data and
      computational meQTL analysis to support HLA-region susceptibility
      architecture without implying Mendelian inheritance.
diagnosis:
- name: Integrated HISORt and IgG4-SC diagnostic criteria
  description: >-
    Diagnosis integrates histology, imaging/cholangiography, serum IgG4,
    other-organ involvement, and response to immunosuppressive therapy, with
    careful exclusion of malignancy.
  results: >-
    Bile-duct narrowing or wall thickening plus supportive serology,
    histopathology, other IgG4-related organ involvement, and/or treatment
    response supports IgG4-SC.
  evidence:
  - reference: PMID:40191403
    reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Accurate diagnosis is challenging due to the absence of pathognomonic
      findings but can be achieved using the HISORt criteria (histology,
      imaging, serology, other organ involvement, and response to
      immunosuppressive therapy).
    explanation: >-
      Supports the integrated diagnostic framework and the absence of a single
      pathognomonic test.
  - reference: PMID:41500843
    reference_title: Multicenter Validation Study of the Clinical Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis 2020 in Japan.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      METHODS: We conducted a multicenter validation study to evaluate the
      diagnostic performance of IgG4-SC2020 using clinical data collected from
      1034 patients with IgG4-SC and 447 patients with mimickers, including 143
      with pancreatic cancer, 157 with primary sclerosing cholangitis, and 147
      with cholangiocarcinoma in Japan.
    explanation: >-
      Documents large-scale validation against the main differential mimics.
  - reference: PMID:41500843
    reference_title: Multicenter Validation Study of the Clinical Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis 2020 in Japan.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The sensitivity of IgG4-SC2020 was significantly higher than that of
      IgG4-SC2012 (99.0% vs. 89.1%; p < 0.001).
    explanation: >-
      Supports the improved performance of the 2020 criteria.
- name: Bile IgG4 diagnostic biomarker research
  description: >-
    Bile IgG4 concentration is being evaluated as a diagnostic biomarker for
    differentiating IgG4-SC from PSC, cholangiocarcinoma, and other biliary
    strictures.
  evidence:
  - reference: clinicaltrials:NCT02616705
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The investigators aim to evaluate the sensitivity and specificity of bile
      for the diagnosis of IgG4-SC.
    explanation: >-
      This completed observational study evaluates bile IgG4 as a diagnostic
      biomarker rather than as treatment.
differential_diagnoses:
- name: Primary Sclerosing Cholangitis
  disease_term:
    preferred_term: primary sclerosing cholangitis
    term:
      id: MONDO:0013433
      label: primary sclerosing cholangitis
  description: >-
    PSC can produce similar multifocal bile-duct strictures and cholestatic
    symptoms but is usually not steroid-responsive and has different
    comorbidity and outcome patterns.
  distinguishing_features:
  - IgG4-SC often co-occurs with autoimmune pancreatitis or other IgG4-related organ disease.
  - PSC is strongly associated with inflammatory bowel disease and does not respond to steroid therapy.
  evidence:
  - reference: PMID:30205418
    reference_title: IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although the presentation of IgG4-SC and PSC are similar, the
      comorbidities, treatment response, and outcomes differ significantly, and
      therefore, it is strongly advisable to be familiar with these two diseases
      to make a correct diagnosis.
    explanation: >-
      Supports PSC as a key mimic and highlights distinguishing clinical
      dimensions.
- name: Cholangiocarcinoma
  disease_term:
    preferred_term: cholangiocarcinoma
    term:
      id: MONDO:0019087
      label: cholangiocarcinoma
  description: >-
    Cholangiocarcinoma can mimic focal or hilar IgG4-SC strictures and must be
    excluded before steroid-response is used as diagnostic support.
  distinguishing_features:
  - Tissue sampling, cytology, imaging, and repeat evaluation are needed when malignancy remains possible.
  - Steroid trials should be avoided when neoplasia has not been reasonably excluded.
  evidence:
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cholangiographic findings of IgG4-SC involving the hilar and/or
      intrahepatic bile ducts are similar to those of hilar cholangiocarcinoma
      or primary sclerosing cholangitis (PSC).
    explanation: >-
      Supports cholangiocarcinoma as a central imaging mimic.
  - reference: PMID:30575336
    reference_title: Clinical practice guidelines for IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      If IgG4-SC cannot be clinically ruled out, a patient must not be treated
      with facile steroid therapy but should be referred to a specialized
      medical facility.
    explanation: >-
      Supports caution with empiric steroid trials during the differential
      diagnosis of malignant biliary disease.
treatments:
- name: Glucocorticoids
  description: >-
    First-line anti-inflammatory therapy for active IgG4-related sclerosing
    cholangitis after diagnosis is secure and malignancy has been excluded.
  treatment_term:
    preferred_term: glucocorticoid therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  evidence:
  - reference: PMID:26593290
    reference_title: New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Corticosteroids are the mainstay of treatment with good clinical,
      biochemical, and radiological responses.
    explanation: >-
      Directly supports corticosteroids as first-line therapy.
  - reference: PMID:40191403
    reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      IRC responds well to corticosteroid therapy, though relapses are common,
      necessitating long-term immunosuppressive treatment in many cases.
    explanation: >-
      Supports both treatment response and the need to monitor for relapse.
- name: Rituximab
  description: >-
    B-cell depletion therapy used for relapsing, steroid-dependent, or
    refractory pancreaticobiliary IgG4-related disease, including IgG4-SC.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: rituximab
      term:
        id: NCIT:C1702
        label: Rituximab
  target_mechanisms:
  - target: B Cell and Plasmablast Activation
    treatment_effect: INHIBITS
    description: >-
      Rituximab depletes CD20-positive B-cell lineage populations upstream of
      IgG4-rich tissue inflammation and is used to prolong remission in
      pancreaticobiliary IgG4-related disease.
  evidence:
  - reference: PMID:29526692
    reference_title: Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thirty-seven patients (86%) were in steroid-free remission 6 months after
      rituximab initiation.
    explanation: >-
      Supports rituximab efficacy in pancreaticobiliary IgG4-related disease.
  - reference: PMID:29526692
    reference_title: Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A higher proportion of patients in group 1 had disease relapse (3-year
      event rate, 45%) than in group 2 (3-year event rate, 11%) (P = .034).
    explanation: >-
      Supports maintenance rituximab as relapse-reducing in a pancreaticobiliary
      IgG4-RD cohort.
- name: Azathioprine
  description: >-
    Steroid-sparing immunomodulator used as a remission-induction or
    maintenance option when long-term immunosuppression is needed.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  evidence:
  - reference: PMID:40191403
    reference_title: "Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Steroid-sparing agents for remission induction and maintenance therapy
      comprise immunomodulators, such as azathioprine, as well as B-cell
      depletion therapies, such as rituximab.
    explanation: >-
      This review supports azathioprine as a steroid-sparing immunomodulator
      option in IgG4-related cholangitis.
- name: Biliary Drainage or Stenting
  description: >-
    Endoscopic decompression is used selectively for clinically significant
    obstructive jaundice, cholangitis, or dominant biliary strictures; stents
    should be removed promptly when strictures improve after corticosteroids.
  treatment_term:
    preferred_term: therapeutic procedure
    term:
      id: NCIT:C49236
      label: Therapeutic Procedure
  evidence:
  - reference: PMID:32353060
    reference_title: Management of biliary stricture in patients with IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-eight patients (40.6%) were treated with EBD for biliary stricture
      before CS initiation.
    explanation: >-
      Supports real-world use of endoscopic biliary drainage before
      corticosteroid initiation in a subset of IgG4-SC patients.
  - reference: PMID:32353060
    reference_title: Management of biliary stricture in patients with IgG4-related sclerosing cholangitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Obstructive jaundice can be treated safely with CS alone in patients
      without infection.
    explanation: >-
      Supports selective, rather than automatic, stenting when obstructive
      jaundice is present without infection.
epidemiology:
- name: Older male predominance
  description: >-
    Mayo Clinic cohort data show predominance in older men, consistent with the
    Falcon report's guideline synthesis.
  evidence:
  - reference: PMID:32770464
    reference_title: "The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      RESULTS: We identified 89 patients with IgG4-SC; median age at diagnosis
      was 67 years, 81% were males, and the median follow-up was 5.7 years.
    explanation: >-
      Supports older age and male predominance in a large single-center cohort.
- name: Lower hepatobiliary event rate than matched PSC cohort
  description: >-
    Long-term outcomes appear more favorable than PSC in immunosuppressed
    cohorts, though cirrhosis and cholangiocarcinoma still occur.
  evidence:
  - reference: PMID:32770464
    reference_title: "The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The probability of development of a hepatobiliary adverse event within 10
      years was 11% in the IgG4-SC compared to 45% in the PSC group (P = 0.0001).
    explanation: >-
      Supports a lower long-term risk of cirrhosis or cholangiocarcinoma than
      PSC in the matched Mayo cohort.
datasets:
📚

References & Deep Research

References

14
DOI:10.1002/jhbp.596
Clinical practice guidelines for IgG4-related sclerosing cholangitis
No top-level findings curated for this source.
DOI:10.1002/jhbp.70056
Multicenter validation study of the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020 in Japan
No top-level findings curated for this source.
DOI:10.1007/s00535-020-01714-7
The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience
No top-level findings curated for this source.
DOI:10.1016/j.cgh.2018.02.049
Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin G4-related disease
No top-level findings curated for this source.
DOI:10.1016/j.cld.2015.08.004
New thoughts on immunoglobulin G4-related sclerosing cholangitis
No top-level findings curated for this source.
DOI:10.1038/nrgastro.2016.132
IgG4-related hepatobiliary disease: an overview
No top-level findings curated for this source.
DOI:10.1053/j.gastro.2015.01.041
Association between HLA haplotypes and increased serum levels of IgG4 in patients with primary sclerosing cholangitis
No top-level findings curated for this source.
DOI:10.1055/a-2588-3875
IgG4-related cholangitis
No top-level findings curated for this source.
DOI:10.1093/gastro/goaf032
Management of IgG4-related cholangitis: diagnosis, therapy, and long-term surveillance
No top-level findings curated for this source.
DOI:10.1136/flgastro-2018-101001
Diagnosis and management of IgG4-related disease
No top-level findings curated for this source.
DOI:10.1186/s13148-024-01803-x
Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis
No top-level findings curated for this source.
DOI:10.1371/journal.pone.0232089
Management of biliary stricture in patients with IgG4-related sclerosing cholangitis
No top-level findings curated for this source.
DOI:10.3389/fmed.2026.1732637
IgG4-related sclerosing cholangitis: navigating diagnostic dilemmas and the challenge of relapse
No top-level findings curated for this source.
DOI:10.5009/gnl18085
IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
1. Disease Information
Edison Scientific Literature 41 citations 2026-05-06T22:24:30.309673

1. Disease Information

1.1 What is the disease?

IgG4-SC is an immune-mediated chronic fibroinflammatory cholangitis characterized by bile-duct strictures and wall thickening, lymphoplasmacytic inflammation rich in IgG4-positive plasma cells, fibrosis, and a typically strong response to glucocorticoids. It is widely recognized as the biliary manifestation of IgG4-RD and frequently occurs with type 1 AIP. (kamisawa2019clinicalpracticeguidelines pages 2-4, ali2020thelongtermoutcomes pages 1-2, beuers2025igg4relatedcholangitis pages 1-3)

1.2 Key identifiers (OMIM, Orphanet, ICD-10/ICD-11, MeSH, MONDO)

  • ICD-10 / ICD-11 / MeSH / MONDO / Orphanet / OMIM: Not explicitly provided in the full-text evidence retrievable in this run; therefore these IDs cannot be asserted here without external ontology lookups. (hegade2019diagnosisandmanagement pages 1-2)

1.3 Synonyms and alternative names

  • IgG4-related cholangitis (IRC) (synonym/alternative name) (herta2025managementofigg4related pages 1-2, beuers2025igg4relatedcholangitis pages 1-3)
  • IgG4-associated cholangitis (common earlier terminology in reviews; overlaps with IgG4-SC/IRC concept) (cargill2017igg4relatedsclerosingcholangitis pages 2-4)
  • Broader/related historical umbrella terms for IgG4-RD include IgG4-related sclerosing disease, IgG4-multiorgan lymphoproliferative syndrome, etc. (hegade2019diagnosisandmanagement pages 1-2)

1.4 Evidence source type (individual vs aggregated)

The report is derived from aggregated disease-level resources (clinical practice guidelines, multicenter diagnostic validation, and large cohorts) and selected trial registry entries. (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 1-2, naitoh2026multicentervalidationstudy pages 1-2, NCT02616705 chunk 1)

2. Etiology

2.1 Disease causal factors (mechanistic)

IgG4-SC is best understood as an immune-mediated, antigen-driven fibroinflammatory disease in genetically susceptible individuals. Mechanistically, a dysregulated adaptive immune response (including Th2/Treg-skewed cytokine milieu) promotes B-cell activation and expansion of IgG4+ B cells/plasmablasts, contributing to chronic inflammation and progressive fibrosis. (ren2026igg4relatedsclerosingcholangitis pages 2-3, smit2016newthoughtson pages 12-14)

2.2 Risk factors

Demographic

  • Predominantly affects older men (guideline summary: ~80% male; typical age at diagnosis ~60–70 years; Mayo cohort median 67 years, 81% male). (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 2-4)

Clinical

  • Strong association with type 1 autoimmune pancreatitis (AIP) (≈90% concomitance in guideline summary; 72% with past/present pancreatitis in Mayo cohort). (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 2-4)

Environmental/occupational (evidence limited)

Occupational antigen exposure has been proposed in some cohorts (e.g., high rates of “blue-collar” work reported in certain populations), but robust causal data for IgG4-SC specifically were not available in the retrieved excerpts. (tanaka2019igg4relatedsclerosingcholangitis pages 1-2)

2.3 Protective factors

No protective genetic or environmental factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

Not established in the retrieved evidence. However, the conceptual model emphasizes genetic susceptibility and environmental triggers acting together. (ren2026igg4relatedsclerosingcholangitis pages 2-3)

3. Phenotypes

3.1 Core clinical phenotypes (with suggested HPO terms)

Common presentations and laboratory abnormalities include:

  1. Obstructive jaundice (HPO: Jaundice HP:0000952) (herta2025managementofigg4related pages 1-2, kamisawa2019clinicalpracticeguidelines pages 6-7)
  2. Upper abdominal pain/discomfort (HPO: Abdominal pain HP:0002027) (herta2025managementofigg4related pages 1-2, ali2020thelongtermoutcomes pages 2-4)
  3. Cholestatic liver enzyme elevation (HPO: Elevated alkaline phosphatase HP:0003155; Elevated gamma-glutamyltransferase HP:0031304) (ali2020thelongtermoutcomes pages 2-4)
  4. Biliary strictures (HPO: Bile duct stenosis HP:0031783 [term mapping may vary]) (kamisawa2019clinicalpracticeguidelines pages 2-4, naitoh2026multicentervalidationstudy pages 2-2)
  5. Weight loss (HPO: Weight loss HP:0001824)—also contributes to malignancy mimicry (herta2025managementofigg4related pages 1-2)

Phenotype characteristics: * Typical onset: adult/older adult (no pediatric cases reported in Japan guideline summary). (kamisawa2019clinicalpracticeguidelines pages 6-7) * Variable severity; a meaningful fraction may be asymptomatic at diagnosis (28%) in Japanese experience. (kamisawa2019clinicalpracticeguidelines pages 6-7)

3.2 Quality of life impact

Specific QoL instruments (SF-36/EQ-5D/PROMIS) were not reported in the retrieved evidence for IgG4-SC.

4. Genetic/Molecular Information

4.1 Causal genes

No monogenic causal gene for IgG4-SC was identified in the retrieved evidence; the condition is best supported as complex immune-mediated with susceptibility signals rather than Mendelian inheritance. (ren2026igg4relatedsclerosingcholangitis pages 2-3)

4.2 Susceptibility genetics / loci (strength: moderate)

  • Whole-blood methylation/genotyping study in IgG4-SC showed a strong HLA-region signal in meQTL analyses, implicating loci including HLA-DQB2, HLA-DPA1, HLA-F, HLA-DRA in shaping methylation patterns. (noble2025epigeneticageacceleration pages 1-2)
  • Related PSC research demonstrates that elevated IgG4 in PSC associates with specific HLA haplotypes (lower HLA-B08; higher HLA-B07 and DRB1*15), underscoring shared immunogenetic architecture relevant for differential diagnosis contexts. (berntsen2015associationbetweenhla pages 1-1)

4.3 Epigenetic information (recent “omics”)

Noble et al. profiled whole-blood DNA methylation in 47 IgG4-SC, 65 PSC, 64 UC, 88 controls and found: * 19 significant methylation differences vs controls in IgG4-SC (38 in PSC). * Epigenetic age acceleration in IgG4-SC (not PSC/UC). * Dysregulated methylation in inflammatory genes including IFNAR1, TXK, HERC6, etc. (noble2025epigeneticageacceleration pages 1-2)

4.4 Chromosomal abnormalities

Not reported.

5. Environmental Information

No specific toxins, lifestyle exposures, or infectious triggers were established in the retrieved evidence for IgG4-SC. (ren2026igg4relatedsclerosingcholangitis pages 2-3)

6. Mechanism / Pathophysiology

6.1 Current mechanistic model (causal chain)

  1. Predisposition/trigger: genetic susceptibility and possible environmental triggers (incompletely defined). (ren2026igg4relatedsclerosingcholangitis pages 2-3)
  2. Immune activation: Th2/Treg-skewed responses with B-cell activation; oligoclonal expansion of IgG4+ plasmablasts. (ren2026igg4relatedsclerosingcholangitis pages 2-3, smit2016newthoughtson pages 12-14)
  3. Tissue inflammation: lymphoplasmacytic infiltrate rich in IgG4+ plasma cells; formation of fibroinflammatory lesions causing biliary wall thickening/strictures. (herta2025managementofigg4related pages 1-2, smit2016newthoughtson pages 6-8)
  4. Fibrosis and remodeling: storiform fibrosis and profibrotic cytokine signaling (e.g., TGF-β) contribute to progressive stricturing and potential secondary biliary cirrhosis in a minority. (ren2026igg4relatedsclerosingcholangitis pages 2-3, ali2020thelongtermoutcomes pages 7-8)

6.2 Key immune cells (suggested CL terms)

  • CD4-positive T cell (CL:0000624)
  • Regulatory T cell (Treg) (CL:0000815)
  • B cell (CL:0000236)
  • Plasmablast/plasma cell (CL:0000980 / CL:0000786) Mechanistic support for T-cell/B-cell involvement and plasmablast expansion is described in mechanistic reviews. (ren2026igg4relatedsclerosingcholangitis pages 2-3, smit2016newthoughtson pages 12-14)

6.3 Key biological processes (suggested GO terms)

  • GO:0006954 inflammatory response
  • GO:0006955 immune response
  • GO:0042113 B cell activation
  • GO:0006959 humoral immune response
  • GO:0042060 wound healing / fibrosis-related processes (fibrogenesis) These are consistent with the described immune activation and fibroinflammatory phenotype. (ren2026igg4relatedsclerosingcholangitis pages 2-3, smit2016newthoughtson pages 12-14)

6.4 Histopathology (defining features)

Diagnostic histology requires combinations of: * Dense lymphoplasmacytic infiltrate * Storiform fibrosis * Obliterative phlebitis with IgG4+ plasma cell thresholds of >10/HPF (biopsy) or >50/HPF (resection) and IgG4+/IgG+ ratio >0.4. (herta2025managementofigg4related pages 1-2, smit2016newthoughtson pages 6-8)

7. Anatomical Structures Affected

7.1 Organ/tissue level (suggested UBERON terms)

  • Extrahepatic bile duct (UBERON:0003707)
  • Intrahepatic bile duct (UBERON:0003708)
  • Liver (UBERON:0002107)
  • Often associated organ involvement: pancreas (UBERON:0001264) via type 1 AIP. (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 2-4)

7.2 Localization patterns

IgG4-SC has diverse cholangiographic patterns; Japanese guidance describes four cholangiographic types, with national survey frequencies: type 1 64%, type 2a 5%, type 2b 8%, type 3 10%, type 4 10%. (kamisawa2019clinicalpracticeguidelines pages 2-4)

8. Temporal Development

8.1 Onset

Typically adult/older adult onset; Japan guideline reports no pediatric/adolescent cases. (kamisawa2019clinicalpracticeguidelines pages 6-7)

8.2 Progression/course

Course is often responsive to steroids but relapsing. Reviews cite relapse rates commonly 30–50% despite high initial response, and post-steroid relapse rates around 40–50% in cited studies. (ren2026igg4relatedsclerosingcholangitis pages 2-3, hegade2019diagnosisandmanagement pages 4-5)

9. Inheritance and Population

9.1 Epidemiology

Japan guideline estimates prevalence 2.0 per 100,000 (~2,500 patients) and extrapolated prevalence/incidence based on AIP data of 1.8 per 100,000 and 0.5 per 100,000, respectively. (kamisawa2019clinicalpracticeguidelines pages 6-7)

9.2 Population demographics

  • Sex ratio: ~80% male (Japan guideline), 81% male in Mayo cohort. (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 2-4)
  • Typical age: 60–70s. (kamisawa2019clinicalpracticeguidelines pages 6-7, ali2020thelongtermoutcomes pages 2-4)

9.3 Inheritance pattern

No Mendelian inheritance is established; evidence supports a complex immune-mediated condition with genetic susceptibility signals. (ren2026igg4relatedsclerosingcholangitis pages 2-3)

10. Diagnostics

10.1 Clinical criteria and diagnostic frameworks

HISORt

HISORt integrates Histology, Imaging, Serology, Other organ involvement, and Response to therapy; it is emphasized because no single pathognomonic test exists and mimics are common. (herta2025managementofigg4related pages 1-2, smit2016newthoughtson pages 6-8)

Japanese clinical diagnostic criteria (2012; revision 2020)

The IgG4-SC2020 criteria include six domains: bile-duct narrowing, bile-duct wall thickening, serology, pathology, other-organ involvement, and response to treatment. (naitoh2026multicentervalidationstudy pages 2-2)

A multicenter validation (Japan; 1,034 IgG4-SC and 447 mimickers) found sensitivity 99.0% (2020) vs 89.1% (2012) while maintaining specificity 100% vs pancreatic cancer and cholangiocarcinoma, and 97.5% vs PSC (2020). (naitoh2026multicentervalidationstudy pages 1-2)

10.2 Key diagnostic thresholds and pitfalls

  • Serum IgG4 elevated in ~80% but not diagnostic alone; modest elevations can occur in 10–15% of PSC/CCA; >4× ULN is highly specific but insensitive. (ren2026igg4relatedsclerosingcholangitis pages 2-3)
  • Histology cutoffs: >10/HPF biopsy; >50/HPF resection; IgG4+/IgG+ >0.4. (herta2025managementofigg4related pages 1-2)
  • Tissue pitfalls: IgG4+ cells can appear in PSC/CCA biopsies; thus malignancy must be excluded carefully. (herta2025managementofigg4related pages 1-2, smit2016newthoughtson pages 6-8)

10.3 Differential diagnosis

Primary mimickers: * Cholangiocarcinoma (CCA) * Primary sclerosing cholangitis (PSC) The need to differentiate these is a central theme across guidelines and diagnostic reviews. (herta2025managementofigg4related pages 1-2, kamisawa2019clinicalpracticeguidelines pages 2-4, ren2026igg4relatedsclerosingcholangitis pages 2-3)

10.4 Biomarker development and real-world diagnostic implementation

  • ClinicalTrials.gov observational cohort NCT02616705 assessed bile IgG4 concentration as a diagnostic biomarker to distinguish IgG4-SC from PSC/CCA and other strictures (enrollment 511; completed 2019-09-30). (NCT02616705 chunk 1)

11. Outcome / Prognosis

11.1 Cohort outcomes

In the Mayo Clinic IgG4-SC cohort (n=89; 1999–2018), hepatobiliary adverse events occurred less frequently than in matched PSC patients: 15.6 vs 52.6 events/1000 person-years, with 10-year hepatobiliary event probability 11% vs 45%. Ten-year survival was 79% in IgG4-SC vs 68% in PSC (trend). (ali2020thelongtermoutcomes pages 1-2)

11.2 Cirrhosis and cholangiocarcinoma risk

The Mayo experience excerpt reports progression to cirrhosis in ~5.2–7.5% across reports and an estimated lifetime CCA risk of 3.4% in that cohort; CCA cases occurred 1.5–5.8 years after IgG4-SC diagnosis in that cohort. (ali2020thelongtermoutcomes pages 7-8)

11.3 Prognostic factors

Relapse risk is highlighted as substantial; in pancreaticobiliary IgG4-RD cohorts, relapse risk relates to factors such as younger age and higher post-induction disease activity indices (IgG4-RI) and alkaline phosphatase in one rituximab maintenance analysis. (majumder2018rituximabmaintenancetherapy pages 1-2)

12. Treatment

12.1 First-line: glucocorticoids

Steroids are first-line once diagnosis is confirmed.

Evidence-supported regimens and relapse statistics: * Expert centers use prednisolone 0.5 mg/kg (30–40 mg/day) for 2–4 weeks, then taper by 5 mg steps. (hegade2019diagnosisandmanagement pages 5-6) * Reported post-steroid relapse rates include 40% after an 11-week course and 50% at median 4.6 months after stopping first course in cited studies. (hegade2019diagnosisandmanagement pages 4-5)

MAXO suggestions: * MAXO: glucocorticoid therapy (term label varies by MAXO release).

12.2 Steroid-sparing immunomodulators

Steroid-sparing regimens listed in hepatobiliary IgG4-RD review include: * Azathioprine 2 mg/kg daily * Mycophenolate mofetil 750–1,000 mg BID * Methotrexate 10–25 mg weekly (+ folate) * Tacrolimus (target level 4–11 ng/mL) * Rituximab 1,000 mg at week 0 and week 2 (B-cell depletion) (culver2016igg4relatedhepatobiliarydisease pages 7-8)

MAXO suggestions: * MAXO: immunosuppressive agent administration.

12.3 B-cell depletion: rituximab (real-world implementation)

In pancreaticobiliary IgG4-RD cohorts: * 6-month steroid-free remission after rituximab: 86%. * 3-year relapse/event rate 45% (induction only) vs 11% (maintenance) (P=.034). * Clinically significant infections occurred in 6/43, largely during maintenance. (majumder2018rituximabmaintenancetherapy pages 1-2)

MAXO suggestions: * MAXO: rituximab therapy / B cell depletion therapy.

12.4 Endoscopic management of biliary strictures (real-world)

In a 69-patient IgG4-SC cohort treated with corticosteroids: * 40.6% underwent endoscopic biliary drainage (EBD) before steroids. * Planned stent removal: 84.6% of removals occurred within 1 month after steroids with no early recurrence. * Spontaneous stent dislodgement occurred in 35.7% after steroids; 70% of dislodgements occurred between 2 weeks and 2 months. * Bile-duct stones developed in 4.3% (all in EBD group), and none in steroid-only group (p=0.032). (miyazawa2020managementofbiliary pages 1-2)

Supporting visual tables are available from the paper’s extracted tables. (miyazawa2020managementofbiliary media 3f18bf73, miyazawa2020managementofbiliary media a80fe471, miyazawa2020managementofbiliary media 500893f9)

MAXO suggestions: * MAXO: endoscopic biliary stenting; endoscopic stent removal.

12.5 Emerging/novel therapies

Recent reviews note emerging B-cell–targeting approaches (e.g., anti-CD19), but IgG4-SC–specific primary efficacy data were not retrievable in this run. (herta2025managementofigg4related pages 1-2)

13. Prevention

No established primary prevention strategies are described in the retrieved evidence. Secondary/tertiary prevention centers on early diagnosis to avoid unnecessary surgery and prevent fibrotic complications, plus surveillance for relapse and biliary complications. (herta2025managementofigg4related pages 1-2)

14. Other Species / Natural Disease

No naturally occurring animal disease or zoonotic aspects were identified in the retrieved evidence.

15. Model Organisms

No specific animal models or in vitro models of IgG4-SC were identified in the retrieved evidence.

Recent developments and latest research emphasis (2023–2025 within retrieved sources)

  • Diagnostic criteria modernization: IgG4-SC2020 criteria show markedly improved sensitivity vs 2012 while maintaining high specificity in a large Japanese multicenter validation (published 2026, but directly relevant to the “current understanding”). (naitoh2026multicentervalidationstudy pages 1-2)
  • Epigenetic/omics: First whole-blood methylation study in IgG4-SC identifies disease-specific methylation differences and epigenetic age acceleration; HLA-region meQTL signals suggest genotype–methylome relationships. (noble2025epigeneticageacceleration pages 1-2)
  • Real-world diagnostic biomarker efforts: NCT02616705 tests bile IgG4 as a biomarker to distinguish IgG4-SC from PSC/CCA/other strictures in a large prospective cohort (completed 2019; continued relevance for implementation). (NCT02616705 chunk 1)

Direct abstract-supported quotations (for key claims)

  • IgG4-SC definition/diagnostic challenge and need for consensus guidance: “IgG4‐related sclerosing cholangitis (IgG4‐SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4‐related disease.” (kamisawa2019clinicalpracticeguidelines pages 2-4)
  • HISORt-based diagnostic concept and relapse: “Diagnosis is challenging due to the absence of pathognomonic findings but can be achieved using the HISORt criteria (histology, imaging, serology, other organ involvement, and response to immunosuppressive therapy).” (herta2025managementofigg4related pages 1-2)
  • Steroid response but relapse: “IgG4-SC often has a good response to initial steroid therapy, but a high relapse rate during follow-up.” (majumder2018rituximabmaintenancetherapy pages 1-2)

Limitations of this evidence package

  • Formal ontology identifiers (MONDO/MeSH/Orphanet/ICD) and many ontology mappings (HPO/GO/CL/UBERON/MAXO) were not explicitly provided in retrieved full-text sources; ontology suggestions are therefore limited to widely used terms and should be validated against the relevant ontology releases.
  • Several key 2023–2024 primary papers/guidelines relevant to IgG4-SC may be unobtainable in this run (e.g., certain systematic reviews/meta-analyses and some 2023 nationwide relapse/cancer-risk studies), so some “latest” claims (e.g., anti-CD19 trial outcomes in IgG4-RD) are discussed only at a high level.

References

  1. (herta2025managementofigg4related pages 1-2): Toni Herta, Maik Schröder, Dominik Geisel, Cornelius Engelmann, and Frank Tacke. Management of igg4-related cholangitis: diagnosis, therapy, and long-term surveillance. Gastroenterology Report, Apr 2025. URL: https://doi.org/10.1093/gastro/goaf032, doi:10.1093/gastro/goaf032. This article has 1 citations and is from a peer-reviewed journal.

  2. (ali2020thelongtermoutcomes pages 1-2): Ahmad Hassan Ali, Yan Bi, Jorge D. Machicado, Sushil Garg, Ryan J. Lennon, Lizhi Zhang, Naoki Takahashi, Elizabeth J. Carey, Keith D. Lindor, J. Gage Buness, James H. Tabibian, and Suresh T. Chari. The long-term outcomes of patients with immunoglobulin g4-related sclerosing cholangitis: the mayo clinic experience. Journal of Gastroenterology, 55:1087-1097, Aug 2020. URL: https://doi.org/10.1007/s00535-020-01714-7, doi:10.1007/s00535-020-01714-7. This article has 37 citations and is from a domain leading peer-reviewed journal.

  3. (majumder2018rituximabmaintenancetherapy pages 1-2): Shounak Majumder, Sonmoon Mohapatra, Ryan J. Lennon, Guilherme Piovezani Ramos, Neil Postier, Ferga C. Gleeson, Michael J. Levy, Randall K. Pearson, Bret T. Petersen, Santhi Swaroop Vege, Suresh T. Chari, Mark D. Topazian, and Thomas E. Witzig. Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin g4-related disease. Clinical Gastroenterology and Hepatology, 16:1947-1953, Dec 2018. URL: https://doi.org/10.1016/j.cgh.2018.02.049, doi:10.1016/j.cgh.2018.02.049. This article has 101 citations and is from a domain leading peer-reviewed journal.

  4. (kamisawa2019clinicalpracticeguidelines pages 6-7): Terumi Kamisawa, Takahiro Nakazawa, Susumu Tazuma, Yoh Zen, Atsushi Tanaka, Hirotaka Ohara, Takashi Muraki, Kazuo Inui, Dai Inoue, Takayoshi Nishino, Itaru Naitoh, Takao Itoi, Kenji Notohara, Atsushi Kanno, Kensuke Kubota, Kenji Hirano, Hiroyuki Isayama, Kyoko Shimizu, Toshio Tsuyuguchi, Tooru Shimosegawa, Shigeyuki Kawa, Tsutomu Chiba, Kazuichi Okazaki, Hajime Takikawa, Wataru Kimura, Michiaki Unno, and Masahiro Yoshida. Clinical practice guidelines for igg4‐related sclerosing cholangitis. Journal of Hepato-Biliary-Pancreatic Sciences, 26:9-42, Jan 2019. URL: https://doi.org/10.1002/jhbp.596, doi:10.1002/jhbp.596. This article has 225 citations and is from a peer-reviewed journal.

  5. (ali2020thelongtermoutcomes pages 2-4): Ahmad Hassan Ali, Yan Bi, Jorge D. Machicado, Sushil Garg, Ryan J. Lennon, Lizhi Zhang, Naoki Takahashi, Elizabeth J. Carey, Keith D. Lindor, J. Gage Buness, James H. Tabibian, and Suresh T. Chari. The long-term outcomes of patients with immunoglobulin g4-related sclerosing cholangitis: the mayo clinic experience. Journal of Gastroenterology, 55:1087-1097, Aug 2020. URL: https://doi.org/10.1007/s00535-020-01714-7, doi:10.1007/s00535-020-01714-7. This article has 37 citations and is from a domain leading peer-reviewed journal.

  6. (smit2016newthoughtson pages 6-8): Wouter L. Smit, Emma L. Culver, and Roger W. Chapman. New thoughts on immunoglobulin g4-related sclerosing cholangitis. Clinics in liver disease, 20 1:47-65, Feb 2016. URL: https://doi.org/10.1016/j.cld.2015.08.004, doi:10.1016/j.cld.2015.08.004. This article has 21 citations and is from a peer-reviewed journal.

  7. (ren2026igg4relatedsclerosingcholangitis pages 2-3): Xiangxiang Ren, Xiaoshi Jin, Litao Liu, and Meng Zhang. Igg4-related sclerosing cholangitis: navigating diagnostic dilemmas and the challenge of relapse. Frontiers in Medicine, 13:1732637, Feb 2026. URL: https://doi.org/10.3389/fmed.2026.1732637, doi:10.3389/fmed.2026.1732637. This article has 0 citations.

  8. (naitoh2026multicentervalidationstudy pages 2-2): Itaru Naitoh, Takahiro Nakazawa, Kensuke Kubota, Takayoshi Nishino, Akira Nakamura, Dai Inoue, Takanori Sano, Kazuhiro Kikuta, Yusuke Kurita, Kazuro Chiba, Tsukasa Ikeura, Hiroyuki Matsubayashi, Takuya Ishikawa, Masaki Kuwatani, Terumi Kamisawa, Ichiro Yasuda, Mitsuhiro Kawano, and Atsushi Masamune. Multicenter validation study of the clinical diagnostic criteria for igg4 ‐related sclerosing cholangitis 2020 in japan. Journal of Hepato-Biliary-Pancreatic Sciences, 33:294-303, Jan 2026. URL: https://doi.org/10.1002/jhbp.70056, doi:10.1002/jhbp.70056. This article has 3 citations and is from a peer-reviewed journal.

  9. (naitoh2026multicentervalidationstudy pages 1-2): Itaru Naitoh, Takahiro Nakazawa, Kensuke Kubota, Takayoshi Nishino, Akira Nakamura, Dai Inoue, Takanori Sano, Kazuhiro Kikuta, Yusuke Kurita, Kazuro Chiba, Tsukasa Ikeura, Hiroyuki Matsubayashi, Takuya Ishikawa, Masaki Kuwatani, Terumi Kamisawa, Ichiro Yasuda, Mitsuhiro Kawano, and Atsushi Masamune. Multicenter validation study of the clinical diagnostic criteria for igg4 ‐related sclerosing cholangitis 2020 in japan. Journal of Hepato-Biliary-Pancreatic Sciences, 33:294-303, Jan 2026. URL: https://doi.org/10.1002/jhbp.70056, doi:10.1002/jhbp.70056. This article has 3 citations and is from a peer-reviewed journal.

  10. (kamisawa2019clinicalpracticeguidelines pages 2-4): Terumi Kamisawa, Takahiro Nakazawa, Susumu Tazuma, Yoh Zen, Atsushi Tanaka, Hirotaka Ohara, Takashi Muraki, Kazuo Inui, Dai Inoue, Takayoshi Nishino, Itaru Naitoh, Takao Itoi, Kenji Notohara, Atsushi Kanno, Kensuke Kubota, Kenji Hirano, Hiroyuki Isayama, Kyoko Shimizu, Toshio Tsuyuguchi, Tooru Shimosegawa, Shigeyuki Kawa, Tsutomu Chiba, Kazuichi Okazaki, Hajime Takikawa, Wataru Kimura, Michiaki Unno, and Masahiro Yoshida. Clinical practice guidelines for igg4‐related sclerosing cholangitis. Journal of Hepato-Biliary-Pancreatic Sciences, 26:9-42, Jan 2019. URL: https://doi.org/10.1002/jhbp.596, doi:10.1002/jhbp.596. This article has 225 citations and is from a peer-reviewed journal.

  11. (ali2020thelongtermoutcomes pages 7-8): Ahmad Hassan Ali, Yan Bi, Jorge D. Machicado, Sushil Garg, Ryan J. Lennon, Lizhi Zhang, Naoki Takahashi, Elizabeth J. Carey, Keith D. Lindor, J. Gage Buness, James H. Tabibian, and Suresh T. Chari. The long-term outcomes of patients with immunoglobulin g4-related sclerosing cholangitis: the mayo clinic experience. Journal of Gastroenterology, 55:1087-1097, Aug 2020. URL: https://doi.org/10.1007/s00535-020-01714-7, doi:10.1007/s00535-020-01714-7. This article has 37 citations and is from a domain leading peer-reviewed journal.

  12. (hegade2019diagnosisandmanagement pages 5-6): Vinod S Hegade, Maria B Sheridan, and Matthew T Huggett. Diagnosis and management of igg4-related disease. Frontline Gastroenterology, 10:275-283, Oct 2019. URL: https://doi.org/10.1136/flgastro-2018-101001, doi:10.1136/flgastro-2018-101001. This article has 46 citations and is from a peer-reviewed journal.

  13. (hegade2019diagnosisandmanagement pages 4-5): Vinod S Hegade, Maria B Sheridan, and Matthew T Huggett. Diagnosis and management of igg4-related disease. Frontline Gastroenterology, 10:275-283, Oct 2019. URL: https://doi.org/10.1136/flgastro-2018-101001, doi:10.1136/flgastro-2018-101001. This article has 46 citations and is from a peer-reviewed journal.

  14. (miyazawa2020managementofbiliary pages 1-2): Masaki Miyazawa, Hajime Takatori, Kazunori Kawaguchi, Kazuya Kitamura, Kuniaki Arai, Koichiro Matsuda, Takeshi Urabe, Katsuhisa Inamura, Takuya Komura, Hideki Mizuno, Uichiro Fuchizaki, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, and Shuichi Kaneko. Management of biliary stricture in patients with igg4-related sclerosing cholangitis. PLoS ONE, 15:e0232089, Apr 2020. URL: https://doi.org/10.1371/journal.pone.0232089, doi:10.1371/journal.pone.0232089. This article has 18 citations and is from a peer-reviewed journal.

  15. (beuers2025igg4relatedcholangitis pages 1-3): Ulrich Beuers and David C. Trampert. Igg4-related cholangitis. Seminars in Liver Disease, May 2025. URL: https://doi.org/10.1055/a-2588-3875, doi:10.1055/a-2588-3875. This article has 1 citations and is from a peer-reviewed journal.

  16. (hegade2019diagnosisandmanagement pages 1-2): Vinod S Hegade, Maria B Sheridan, and Matthew T Huggett. Diagnosis and management of igg4-related disease. Frontline Gastroenterology, 10:275-283, Oct 2019. URL: https://doi.org/10.1136/flgastro-2018-101001, doi:10.1136/flgastro-2018-101001. This article has 46 citations and is from a peer-reviewed journal.

  17. (cargill2017igg4relatedsclerosingcholangitis pages 2-4): T. Cargill, E. Culver, and R. Chapman. Igg4-related sclerosing cholangitis. Biliary Disease, pages 243-261, Jan 2017. URL: https://doi.org/10.1007/978-3-319-50168-0_12, doi:10.1007/978-3-319-50168-0_12. This article has 29 citations.

  18. (NCT02616705 chunk 1): Lewis R. Roberts. Bile Usefulness for Detecting IgG4-related Sclerosing Cholangitis. Mayo Clinic. 2015. ClinicalTrials.gov Identifier: NCT02616705

  19. (smit2016newthoughtson pages 12-14): Wouter L. Smit, Emma L. Culver, and Roger W. Chapman. New thoughts on immunoglobulin g4-related sclerosing cholangitis. Clinics in liver disease, 20 1:47-65, Feb 2016. URL: https://doi.org/10.1016/j.cld.2015.08.004, doi:10.1016/j.cld.2015.08.004. This article has 21 citations and is from a peer-reviewed journal.

  20. (tanaka2019igg4relatedsclerosingcholangitis pages 1-2): Atsushi Tanaka. Igg4-related sclerosing cholangitis and primary sclerosing cholangitis. Gut and Liver, 13:300-307, May 2019. URL: https://doi.org/10.5009/gnl18085, doi:10.5009/gnl18085. This article has 84 citations and is from a peer-reviewed journal.

  21. (noble2025epigeneticageacceleration pages 1-2): Alexandra Noble, Rodrigo Motta, Silvia Cabras, Belen Moron Flores, Jan Nowak, Aleksandra Glapa-Nowak, Alessandra Geremia, Jack Satsangi, and Emma Culver. Epigenetic age acceleration and methylation differences in igg4-related cholangitis and primary sclerosing cholangitis. Clinical Epigenetics, Jan 2025. URL: https://doi.org/10.1186/s13148-024-01803-x, doi:10.1186/s13148-024-01803-x. This article has 2 citations and is from a peer-reviewed journal.

  22. (berntsen2015associationbetweenhla pages 1-1): Natalie L. Berntsen, Olav Klingenberg, Brian D. Juran, Maria Benito de Valle, Björn Lindkvist, Konstantinos N. Lazaridis, Kirsten Muri Boberg, Tom H. Karlsen, and Johannes Roksund Hov. Association between hla haplotypes and increased serum levels of igg4 in patients with primary sclerosing cholangitis. Gastroenterology, 148 5:924-927.e2, May 2015. URL: https://doi.org/10.1053/j.gastro.2015.01.041, doi:10.1053/j.gastro.2015.01.041. This article has 59 citations and is from a highest quality peer-reviewed journal.

  23. (culver2016igg4relatedhepatobiliarydisease pages 7-8): Emma L. Culver and Roger W. Chapman. Igg4-related hepatobiliary disease: an overview. Nature Reviews Gastroenterology &Hepatology, 13:601-612, Oct 2016. URL: https://doi.org/10.1038/nrgastro.2016.132, doi:10.1038/nrgastro.2016.132. This article has 109 citations.

  24. (miyazawa2020managementofbiliary media 3f18bf73): Masaki Miyazawa, Hajime Takatori, Kazunori Kawaguchi, Kazuya Kitamura, Kuniaki Arai, Koichiro Matsuda, Takeshi Urabe, Katsuhisa Inamura, Takuya Komura, Hideki Mizuno, Uichiro Fuchizaki, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, and Shuichi Kaneko. Management of biliary stricture in patients with igg4-related sclerosing cholangitis. PLoS ONE, 15:e0232089, Apr 2020. URL: https://doi.org/10.1371/journal.pone.0232089, doi:10.1371/journal.pone.0232089. This article has 18 citations and is from a peer-reviewed journal.

  25. (miyazawa2020managementofbiliary media a80fe471): Masaki Miyazawa, Hajime Takatori, Kazunori Kawaguchi, Kazuya Kitamura, Kuniaki Arai, Koichiro Matsuda, Takeshi Urabe, Katsuhisa Inamura, Takuya Komura, Hideki Mizuno, Uichiro Fuchizaki, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, and Shuichi Kaneko. Management of biliary stricture in patients with igg4-related sclerosing cholangitis. PLoS ONE, 15:e0232089, Apr 2020. URL: https://doi.org/10.1371/journal.pone.0232089, doi:10.1371/journal.pone.0232089. This article has 18 citations and is from a peer-reviewed journal.

  26. (miyazawa2020managementofbiliary media 500893f9): Masaki Miyazawa, Hajime Takatori, Kazunori Kawaguchi, Kazuya Kitamura, Kuniaki Arai, Koichiro Matsuda, Takeshi Urabe, Katsuhisa Inamura, Takuya Komura, Hideki Mizuno, Uichiro Fuchizaki, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, and Shuichi Kaneko. Management of biliary stricture in patients with igg4-related sclerosing cholangitis. PLoS ONE, 15:e0232089, Apr 2020. URL: https://doi.org/10.1371/journal.pone.0232089, doi:10.1371/journal.pone.0232089. This article has 18 citations and is from a peer-reviewed journal.