Aortitis

Complex MONDO:0006656 Pathograph 13 Show in embeddings browser Vascular disorder Vasculitis Inflammatory disorder

Aortitis is inflammation of the aortic wall, spanning noninfectious large-vessel vasculitis, clinically isolated surgical-pathology aortitis, infectious aortitis, and drug-induced forms such as G-CSF-associated aortitis. The shared disease axis is aortic wall inflammation with risk for aneurysm, dissection, stenotic or occlusive disease, ischemic complications, and aortic valve involvement, but the required management differs sharply by etiology.

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6
Pathophys.
2
Histopath.
8
Phenotypes
2
Gaps
13
Pathograph
5
Medical Actions
5
Subtypes
1
Differentials
1
Datasets
2
Trials
1
Models
2
Deep Research
◆

Subtypes

5
Clinically isolated aortitis
Histology-confirmed aortitis without known systemic inflammatory or infectious disease; many cases are discovered incidentally during aortic surgery.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"The prevalence of aortitis was 10.6% (n = 57), of which 75% were clinically isolated."
This surgical cohort identifies clinically isolated aortitis as the majority subtype among histology-confirmed aortitis cases.
Large-vessel vasculitis-associated aortitis
Aortitis associated with giant cell arteritis, Takayasu arteritis, or other large- and variable-vessel vasculitides.
Show evidence (1 reference)
DOI:10.3390/jcm13216364 SUPPORT Other
"Large vessel vasculitis (LVV), particularly giant cell arteritis (GCA) and Takayasu arteritis (TAK), has garnered attention due to its significant morbidity and mortality."
This review anchors GCA and Takayasu arteritis as major large-vessel vasculitis contexts relevant to aortitis.
Infectious aortitis
Aortitis caused by microbial infection of the aortic wall, often presenting with aneurysm or structural aortic abnormalities and requiring urgent antimicrobial and vascular-surgery evaluation.
Show evidence (1 reference)
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
This multicenter aortitis cohort identifies infectious aortitis cases and their causative organisms.
G-CSF-associated drug-induced aortitis
A rare adverse event after granulocyte-colony stimulating factor exposure, most often reported in oncology supportive-care settings and occasionally in healthy stem-cell donors.
Show evidence (1 reference)
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"Recombinant human granulocyte-colony stimulating factors (G-CSF)-induced aortitis is a rare but particularly serious adverse event, commonly seen in cancer patients undergoing chemotherapy."
This literature review supports G-CSF exposure as a drug-induced aortitis subtype, especially in chemotherapy care.
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Discussions and Knowledge Gaps

2
Does postoperative immunosuppression improve aortic outcomes in clinically isolated aortitis?
KNOWLEDGE GAP OPEN disc_aortitis_cia_immunosuppression
Attached to
has_subtypes#Clinically isolated aortitis treatments#Specialist multidisciplinary follow-up and aortic surveillance
Clinically isolated aortitis is often discovered only after resection and carries subsequent vascular risk, but surveillance is better supported than a uniform immunosuppressive regimen. Etiology, residual active inflammation, and surgical selection complicate treatment comparisons; no disease-level efficacy claim was added.
Posed 2026-08-05T00:00:00Z
Show evidence (1 reference)
PMID:40099651 SUPPORT Other
"Surveillance of patients with IA with repeated clinical assessments and imaging is recommended."
Supports surveillance while leaving postoperative immunosuppression unresolved.
Which experimental model can reproduce chronic human aortic inflammation, remodeling, and aneurysm formation?
HUMAN MODEL MISMATCH OPEN disc_aortitis_model_fidelity
Attached to
animal_models#Mouse (Mus musculus)
The human temporal-artery SCID chimera preserves an arterial immune lesion and enables perturbation studies, but its anatomy and time course do not model chronic aortic remodeling. Aortic-tissue and longitudinal models are needed before extrapolating model interventions to aortic outcomes.
Posed 2026-08-05T00:00:00Z
Show evidence (1 reference)
PMID:9185506 SUPPORT Model Organism
"GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo."
Defines what the model supports and, by its temporal-artery anatomy, the principal mismatch.
⚙

Pathophysiology

6
Immune-mediated aortic wall inflammation in large-vessel vasculitis
Large-vessel vasculitis-associated aortitis involves immune-mediated inflammation of the vascular wall, including inflammatory cell accumulation in aortic tissue in Takayasu arteritis.
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology. macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology. granulocyte CL:0000094 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves granulocyte (CL:0000094). CL:0000094 is a cell type from the Cell Ontology. endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology. smooth muscle cell CL:0000192 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves smooth muscle cell (CL:0000192). CL:0000192 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED adaptive immune response GO:0002250 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal adaptive immune response (GO:0002250). GO:0002250 is a biological process from the Gene Ontology. ⚠ ABNORMAL
aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in aorta (UBERON:0000947). UBERON:0000947 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Aortic wall structural remodeling Persistent vascular inflammation contributes to later remodeling and structural complications such as aneurysm, dissection, or ischemia.
Tenascin-C and IL-6 inflammatory persistence Immune-mediated giant-cell aortitis is associated with lesion-localized tenascin-C accumulation and stromal inflammatory modulation.
Show evidence (3 references)
DOI:10.3390/jcm13216364 SUPPORT Other
"Both conditions involve immune-mediated inflammation of the vascular wall, despite differing in epidemiology and presentation."
Supports immune-mediated vascular-wall inflammation as a shared mechanism in the GCA/TAK large-vessel vasculitis context.
DOI:10.1177/000331970005100705 SUPPORT Human Clinical
"CD68 (macrophages), CD15 (granulocytes), von Willebrand factor (endothelial cells), and alpha-smooth muscle actin (smooth muscle cells)."
Directly supports macrophage and granulocyte involvement in affected aortic wall tissue in Takayasu arteritis.
DOI:10.1177/000331970005100705 SUPPORT Human Clinical
"(endothelial cells), and alpha-smooth muscle actin (smooth muscle cells)."
Supports endothelial-cell and smooth-muscle-cell assessment in affected aortic wall tissue.
Infectious aortic wall infection
Infectious aortitis is initiated by microbial infection of native aortic tissue. Acute reported causes include Salmonella species, Staphylococcus species, Streptococcus pneumoniae, and other streptococci; syphilitic and tuberculous forms may be subacute. Infection may produce wall thickening or aneurysmal distortion and a higher-mortality phenotype than noninfectious aortitis.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in aorta (UBERON:0000947). UBERON:0000947 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Aortic aneurysm Infectious wall injury commonly presents with aneurysmal aortic disease.
Show evidence (3 references)
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
Identifies causative organisms in infectious aortitis and supports microbial infection as the upstream etiology.
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P < .001), especially located in the abdominal aorta (69.7% vs 23.1%, P < .001)."
Links infectious aortitis to aneurysmal aortic injury more strongly than noninfectious aortitis in the comparison cohort.
PMID:26775836 SUPPORT Human Clinical
"The syphilitic or tubercular forms can be subacute. When it is caused by Salmonella sp., Staphylococcus sp. or Streptococcus pneumoniae, the aortitis is acute with alarming symptoms."
Names representative acute microbial causes and distinguishes subacute syphilitic or tuberculous disease.
G-CSF-associated aortic inflammation
Exogenous G-CSF exposure can trigger aortitis as a serious adverse event, most often detected by CT in the aortic arch and branch vessels.
cytokine-mediated signaling pathway GO:0019221 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal cytokine-mediated signaling pathway (GO:0019221). GO:0019221 is a biological process from the Gene Ontology. ⚠ ABNORMAL inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in aorta (UBERON:0000947). UBERON:0000947 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Aortic wall structural remodeling Rare reported G-CSF-associated cases progressed to aneurysm or dissection.
Show evidence (2 references)
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
Identifies G-CSF exposure, particularly pegfilgrastim, as the most common trigger in the case-review dataset.
PMID:38521841 SUPPORT Human Clinical
"switching from one short-acting G-CSF to another does not prevent recurrence of G-CSF-associated aortitis."
The case supports recurrence after switching short-acting G-CSF preparations and helps explain why re-exposure should be treated cautiously.
Tenascin-C and IL-6 inflammatory persistence
In resected giant-cell, clinically isolated, and IgG4-related aortitis specimens, tenascin-C accumulated in lesions and stromal cells showed phenotypic modulation. Primary human smooth-muscle-cell experiments support a TNC-TLR4/NF-kappaB-IL-6-STAT3 inflammatory loop; this mechanistic component is experimental and not yet a validated therapeutic biomarker.
smooth muscle cell CL:0000192 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves smooth muscle cell (CL:0000192). CL:0000192 is a cell type from the Cell Ontology. fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
cytokine-mediated signaling pathway GO:0019221 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cytokine-mediated signaling pathway (GO:0019221). GO:0019221 is a biological process from the Gene Ontology. ↑ INCREASED
aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in aorta (UBERON:0000947). UBERON:0000947 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Aortic wall structural remodeling Lesion-associated stromal modulation accompanies aortic wall remodeling.
Show evidence (2 references)
PMID:41948935 SUPPORT Human Clinical
"We confirmed these findings histologically using diseased aortas resected from individuals with giant cell arteritis and clinically isolated aortitis."
Confirms lesion-associated findings in human resected aortas.
PMID:41948935 SUPPORT In Vitro
"Mechanistically, our data suggest that TNC promotes a proinflammatory phenotype in primary human SMCs, elevating IL-6 levels partially through the TLR4/NF-κB pathway. IL-6 signaling propagates the proinflammatory loop by activating STAT3."
Supports the proposed signaling loop in primary human smooth-muscle-cell experiments.
Aortic wall structural remodeling
Inflammatory injury can weaken and remodel the aortic wall, producing aneurysm or dissection and driving the need for long-term aortic follow-up.
smooth muscle cell CL:0000192 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves smooth muscle cell (CL:0000192). CL:0000192 is a cell type from the Cell Ontology. fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
extracellular matrix organization GO:0030198 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal extracellular matrix organization (GO:0030198). GO:0030198 is a biological process from the Gene Ontology. ⚠ ABNORMAL
aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in aorta (UBERON:0000947). UBERON:0000947 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Aortic aneurysm Aortic wall remodeling can present as aneurysmal dilation.
Aortic dissection Weakened and inflamed aortic wall can dissect.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
Directly links aortic inflammation to the principal structural complications of aneurysm and dissection.
✶

Histopathology

2
Aortic wall inflammatory infiltrates
Aortitis can show inflammatory infiltrates in the aortic wall, with lymphocytes, dendritic cells, macrophages, granulocytes, endothelial cells, and smooth muscle cells characterized in Takayasu aortic tissue.
Show evidence (1 reference)
DOI:10.1177/000331970005100705 SUPPORT Human Clinical
"All specimens showed distinctive histologic features of Takayasu's arteritis and contained inflammatory infiltrates"
Histologic inflammatory infiltrates in aortic wall tissue support this microscopic aortitis feature.
Histology-confirmed clinically isolated aortitis
Clinically isolated aortitis is often diagnosed through intra-operative aortic sampling rather than through preoperative clinical symptoms.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
Supports intra-operative histologic sampling as a key diagnostic route for clinically isolated aortitis.
⬡

Pathograph

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

8
Cardiovascular 3
Aortic aneurysm HP:0004942 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aortic aneurysm (HP:0004942). HP:0004942 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
The abstract directly names aneurysm as a complication of aortitis.
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P < .001), especially located in the abdominal aorta (69.7% vs 23.1%, P < .001)."
The infectious/noninfectious comparison shows a strong association between infectious aortitis and aortic aneurysm.
Aortic dissection HP:0002647 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aortic dissection (HP:0002647). HP:0002647 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
The abstract directly names dissection as a complication of aortitis.
Aortic regurgitation HP:0001659 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aortic regurgitation (HP:0001659). HP:0001659 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.62186/001c.146456 SUPPORT Human Clinical
"Due to severe aortic regurgitation limiting her activity and aortic root aneurysm"
This case report links giant cell aortitis with severe aortic regurgitation and aortic root aneurysm.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40272133 SUPPORT Human Clinical
"The diagnosis of G-CSF-induced aortitis should be considered in patients with fever after G-CSF treatment, particularly if adequate antibiotic treatment does not lead to improvement."
The case report interpretation explicitly links fever after G-CSF exposure to consideration of G-CSF-induced aortitis.
PMID:34448091 SUPPORT Human Clinical
"If a patient develops a persistent high fever of unknown origin after pegfilgrastim administration, drug-induced aortitis should be considered during investigations for causes of fever."
The case-report conclusion supports persistent high fever as a key clinical clue for pegfilgrastim-induced aortitis.
Other 4
Aortitis HP:6001461 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aortitis (HP:6001461). HP:6001461 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
The abstract defines aortitis as inflammation of the aorta.
Elevated C-reactive protein Elevated circulating C-reactive protein concentration HP:0011227 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating C-reactive protein concentration (HP:0011227). HP:0011227 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40272133 SUPPORT Human Clinical
"After four days, C-reactive protein (CRP) had increased from 104 to 331, but the patient's condition was largely unchanged."
The case report documents marked CRP increase during G-CSF-associated aortitis evaluation.
PMID:34448091 SUPPORT Human Clinical
"Therefore, C-reactive protein (CRP) is currently used to assess disease activity in clinical practice."
The full-text case report notes CRP use for assessing G-CSF-associated aortitis activity.
Elevated erythrocyte sedimentation rate HP:0003565 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated erythrocyte sedimentation rate (HP:0003565). HP:0003565 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36843728 SUPPORT Human Clinical
"The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated, and he also had inflammatory anemia with a hemoglobin of 11.7 g/L."
This giant-cell-aortitis case report documents elevated ESR and CRP in the inflammatory presentation.
Increased circulating IgG4 level HP:0032300 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Increased circulating IgG4 level (HP:0032300). HP:0032300 is a phenotype from the Human Phenotype Ontology.
↑ INCREASED
Show evidence (1 reference)
DOI:10.3389/fimmu.2025.1625456 SUPPORT Other
"IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
Supports elevated serum IgG4 in the parent IgG4-related disease while preserving its nonspecificity for aortitis.
💊

Medical Actions

5
Glucocorticoid therapy for noninfectious aortitis
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: glucocorticoid CHEBI:24261 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses glucocorticoid (CHEBI:24261). CHEBI:24261 is a therapeutic agent from Chemical Entities of Biological Interest. prednisolone CHEBI:8378 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses prednisolone (CHEBI:8378). CHEBI:8378 is a therapeutic agent from Chemical Entities of Biological Interest.
Glucocorticoids are a first-line immunosuppressive treatment backbone for noninfectious large-vessel aortitis contexts, including giant cell arteritis and IgG4-related aortitis/periaortitis.
Show evidence (4 references)
DOI:10.1186/s13063-024-07905-4 SUPPORT Other
"Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates."
Giant cell arteritis is a major large-vessel vasculitis context for aortitis, and this trial protocol identifies glucocorticoids as standard treatment.
PMID:36843728 SUPPORT Human Clinical
"Treatment with high-dose steroids should be initiated as soon as possible to rapidly control the inflammatory symptoms and prevent ischemic complications"
This giant-cell-arteritis/aortitis case report supports high-dose steroid treatment for inflammatory large-vessel disease.
DOI:10.3389/fimmu.2025.1625456 SUPPORT Other
"Glucocorticoids (GCs) are the mainstay of treatment, often combined with immunosuppressants (IMs), while B- and T-cell-targeted therapies are under investigation."
The IgG4-related aortitis review directly supports glucocorticoids as a mainstay treatment for IgG4-related aortitis/periaortitis.
+ 1 more reference
Empiric antimicrobial therapy for infectious aortitis
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Infectious aortitis requires early antimicrobial therapy, initially empiric when microbiologic documentation is pending and then adapted to organism and susceptibility data.
Show evidence (1 reference)
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"Effective empiric antimicrobial therapy, initiated before any microbial documentation, was associated with a decreased mortality"
Supports early empiric antimicrobial therapy as a mortality-associated protective intervention in infectious aortitis.
Tocilizumab for LVV-associated aortitis contexts
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Tocilizumab may be used for large-vessel vasculitis phenotypes associated with aortitis, with clinical remission and glucocorticoid-sparing effects reported in LV-GCA and Takayasu arteritis cohorts.
Show evidence (3 references)
DOI:10.3390/sci7010012 SUPPORT Human Clinical
"Tocilizumab (TCZ) has demonstrated potential efficacy in managing large-vessel (LV) vasculitis such as giant-cell arteritis (GCA) and Takayasu arteritis (TAK)."
Supports tocilizumab as a treatment option in the LVV contexts that can include aortitis.
DOI:10.3390/sci7010012 SUPPORT Human Clinical
"complete imaging resolution was observed in only 18.9% of LV-GCA patients and 21.1% of TAK patients."
The clinical benefit is tempered by incomplete imaging resolution, supporting a partial rather than complete effect on vascular inflammation.
PMID:41531143 SUPPORT Human Clinical
"In this real-world cohort of GCA-associated aortitis, SC TCZ showed slightly greater effectiveness than IV TCZ in achieving EULAR-defined remission, whereas no significant differences were observed between both routes regarding imaging remission."
Supports route-specific comparative outcomes in GCA-associated aortitis without claiming superiority for imaging remission.
Upadacitinib for giant-cell-arteritis contexts
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Upadacitinib is a JAK inhibitor with phase III evidence for giant cell arteritis, a major large-vessel vasculitis context that can include aortitis. Its long-term effect on aortic remodeling remains uncertain.
Show evidence (1 reference)
PMID:40174237 SUPPORT Human Clinical
"In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg - but not 7.5 mg - with a 26-week glucocorticoid taper showed efficacy superior to that of placebo with a 52-week glucocorticoid taper."
The SELECT-GCA phase III trial supports upadacitinib efficacy in GCA, but not specifically aortic remodeling or aortitis endpoints.
Specialist multidisciplinary follow-up and aortic surveillance
Action: clinical assessmentNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is clinical assessment, annotated with Clinical Evaluation (NCIT:C124351). NCIT:C124351 is a clinical intervention from the NCI Thesaurus. Ontology label: Clinical Evaluation NCIT:C124351
Patients with aortitis require specialist follow-up because of increased re-intervention risk and late aortic complications.
Show evidence (3 references)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Due to the increased re-intervention in aortitis, specialist multi-disciplinary follow-up and aortitis centres should be formed."
Supports specialist multidisciplinary follow-up for aortitis after major aortic surgery.
PMID:40099651 SUPPORT Other
"Surveillance of patients with IA with repeated clinical assessments and imaging is recommended."
This review supports repeated clinical and imaging surveillance for isolated aortitis.
PMID:41365838 SUPPORT Human Clinical
"Baseline aortic diameter was the strongest predictor of aortic expansion (β = 0.088; P = 0.006) and incident aortic dilation (adjusted hazard ratio 3.9; 95% CI: 2.0, 7.3)."
Supports longitudinal dimension monitoring in a 157-patient multicenter GCA cohort.
🌍

Environmental Factors

2
Granulocyte-colony stimulating factor exposure
G-CSF exposure, particularly pegfilgrastim in reported cases, can trigger drug-induced aortitis.
Show evidence (1 reference)
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
Identifies pegfilgrastim as the most frequently reported G-CSF exposure in G-CSF-associated aortitis.
Mechanism Target:
TRIGGERS G-CSF-associated aortic inflammation — The node is named for this drug, so the exposure is the node's own content rather than something inferred onto it, and direct is the honest link type for a drug-induced inflammation with no intervening disease. The strongest item is the second: patients re-exposed to the drug developed the aortitis again, and the review concludes that neither repeated use nor a change of preparation rules out recurrence. Recurrence on re-exposure is the classic argument for drug causation and is what lifts this link above an association. Note for anyone re-checking this entry that the reference is a DOI, and the reference validator skips DOI-prefixed snippets, so every quote here was verified against the cached record by hand.
Show evidence (3 references)
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"(G-CSF)-induced aortitis is a rare but particularly serious adverse event, commonly seen in cancer patients undergoing chemotherapy"
States drug-induced aortitis as an adverse event of this drug rather than assuming it, which is the claim this edge makes.
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"This indicated that patients with a history of G-CSF-induced aortitis, whether through repeated use or changes in dosage form, cannot rule out the possibility of recurrent G-CSF-induced aortitis"
The review's conclusion from its re-administration cases: the aortitis returns when the drug does, and switching preparation does not prevent it. Recurrence on re-exposure is the strongest causal design available for a drug, and it is what this link rests on. Two limits belong with it rather than after it: the authors qualify this very sentence by noting that reporting bias means the possibility still needs further validation, and the underlying numbers are small, three re-administrations of the same preparation plus two switches.
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
Names pegfilgrastim as the G-CSF most frequently associated with aortitis. It settles which agent within an association it takes as given, so it supports the edge by assuming it rather than by showing it, and it stays partial for that reason now that the two items above carry the claim directly.
Current tobacco smoking
exposure to tobacco smoking ECTO:6000029 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to tobacco smoking (ECTO:6000029). ECTO:6000029 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Current smoking was associated with histology-confirmed aortitis in a major aortic surgery cohort.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Multivariate logistic regression identified increased age, female sex, current smoking, and other inflammatory diseases as significantly associated with aortitis"
Supports current smoking as a clinical risk association in the surgical aortitis cohort.
Mechanism Target:
PREDISPOSES Aortic wall structural remodeling — The target was forced by the graph as much as chosen: every inflammatory node in this entry is etiology-specific, naming large-vessel vasculitis, infection, G-CSF or IgG4, so wall remodeling is the only etiology-agnostic node available to an exposure that belongs to none of those arms. The cited regression associates smoking with aortitis as a whole and names no mechanism, so nothing in the evidence points anywhere in particular; remodeling is where a chronic inhaled exposure is understood to land. Intermediates unknown for the same reason. This is the weakest link in the tranche and is graded to say so.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Multivariate logistic regression identified increased age, female sex, current smoking, and other inflammatory diseases as significantly associated with aortitis"
A multivariate regression identifying current smoking, along with age, female sex and other inflammatory diseases, as significantly associated with aortitis. It establishes that smokers are over-represented and says nothing about the aortic wall.
🔬

Diagnosis

3
Histologic aortic wall assessment
Intra-operative aortic sampling can diagnose clinically isolated aortitis that may be missed clinically.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Aortic wall inflammation on histology supports the diagnosis.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
Supports histologic assessment as a diagnostic approach in surgical aortitis and clinically isolated aortitis.
Large-vessel vascular imaging
CTA, ultrasound, MRI, and FDG-PET are used to detect large-vessel vasculitis activity, wall thickening, and aortic or branch-vessel involvement.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Vessel-wall thickening or FDG uptake supports active vascular inflammation.
Show evidence (2 references)
DOI:10.3390/jcm13216364 SUPPORT Other
"Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
Supports vascular imaging as a diagnostic method for large-vessel vasculitis-associated aortitis.
DOI:10.1136/rmdopen-2023-003379 SUPPORT Human Clinical
"Ultrasound, MRI and FDG-PET revealed a good performance for the diagnosis of GCA."
Supports ultrasound, MRI, and FDG-PET as evidence-backed imaging tools in giant-cell-arteritis large-vessel disease.
Infectious versus noninfectious etiology assessment
Evaluation should distinguish infectious aortitis from noninfectious aortitis because treatment and mortality risk differ.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Microbiologic evidence and aortic imaging pattern help classify etiology.
Show evidence (2 references)
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"Determining the etiology of aortitis is often challenging, in particular to distinguish infectious aortitis (IA) and noninfectious aortitis (NIA)."
Supports explicit infectious/noninfectious etiologic assessment during aortitis diagnosis.
DOI:10.3390/jcm13216364 SUPPORT Other
"Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
Supports vascular imaging as a central diagnostic tool when evaluating aortitis and large-vessel vasculitis.
🩻

Imaging Findings

2
Aortic wall thickening on cross-sectional imaging
Circumferential aortic-wall thickening on CTA or MRI supports active inflammatory aortic disease but is not pathognomonic and must be interpreted with clinical, microbiologic, and other imaging evidence.
Ct Diffuse
Aortic wall thickening aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON)
No sufficiently specific HP or NCIT term was identified at review; ontology term request is needed.
Show evidence (1 reference)
DOI:10.3390/jcm13216364 SUPPORT Other
"Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
Supports wall thickening as a suggestive, not pathognomonic, large-vessel imaging feature.
Increased aortic FDG uptake on PET/CT
Increased 18F-FDG uptake in the aorta with or without major branches is used to assess inflammatory activity and treatment response, but uptake is nonspecific and imaging normalization may lag behind clinical remission.
Pet Diffuse
Increased aortic fluorodeoxyglucose uptake aorta UBERON:0000947 Uberon multi-species anatomy ontology (UBERON)
No sufficiently specific HP or NCIT term was identified at review; ontology term request is needed.
Show evidence (1 reference)
PMID:41186891 SUPPORT Human Clinical
"The main diagnostic method was the positron emission tomography (PET), showing a non-specific increase in 18F-FDG uptake of the aorta with/without its major branches."
Supports the finding and explicitly preserves its nonspecificity.
📈

Progression

5
Acute outcomes after open thoracic aortic aneurysm repair
In a United States administrative cohort of open thoracic aortic aneurysm repairs, a coded diagnosis of noninfectious aortitis was independently associated with worse in-hospital outcomes. This is a post-intervention, selected-population association rather than disease incidence or causality.
Show evidence (1 reference)
PMID:42175556 SUPPORT Human Clinical
"Following multivariable adjustment, aortitis was independently associated with increased odds of in-hospital mortality (AOR: 1.45, 95% CI: 1.14-1.84), major adverse cardiac and cerebrovascular events (AOR: 1.40, 95% CI: 1.15-1.70), neurologic complications (AOR: 1.33, 95% CI: 1.05-1.70), and..."
Reports adjusted acute outcome associations in a national administrative cohort; it does not establish aortitis as the cause of each outcome.
Asymptomatic discovery during aortic surgery
Clinically isolated aortitis
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
Supports asymptomatic surgical discovery as an important presentation mode for clinically isolated aortitis.
Re-intervention after aortitis-associated aortic surgery
Re-operation risk is higher in aortitis than in non-aortitis surgical comparators.
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"The re-operation rate in aortitis was twice that of non-aortitis patients (17.5% vs. 9.4%, p = 0.054)."
Quantifies higher post-surgical re-operation rates in the aortitis cohort.
Accelerated thoracic aortic aneurysm growth in inflammatory aortitis
A small retrospective matched study found faster preoperative aneurysm growth with histology-confirmed aortitis, especially clinically isolated aortitis; prospective validation is needed.
Show evidence (1 reference)
PMID:42276733 SUPPORT Human Clinical
"The mean growth rate was significantly higher in the aortitis group (0.177±0.01 mm/month; 2.12 mm/year) compared with controls (0.039±0.02 mm/month; 0.47 mm/year), representing a 4.5-fold acceleration (p<0.001)."
Supports an association with faster growth in 23 aortitis cases and 42 matched controls.
Discordant clinical and imaging remission
Clinical or laboratory improvement does not reliably imply normalization of vascular imaging, supporting multimodal longitudinal assessment.
Show evidence (1 reference)
PMID:41186891 SUPPORT Human Clinical
"After a mean follow-up of 39.2 ± 26.7 months, 72 patients (53.7%) experienced clinical remission, 64 (47.8%) complete remission and only 15 (11.2%) imaging remission."
Quantifies remission discordance in a single referral-center cohort.
📊

Prevalence

1
Single-center major aortic surgery cohort with high histology sampling
10.6%
Show evidence (1 reference)
DOI:10.3390/jcdd11120405 SUPPORT Human Clinical
"The prevalence of aortitis was 10.6% (n = 57), of which 75% were clinically isolated."
Provides the observed prevalence of histology-confirmed aortitis in a high-sampling surgical cohort.
🌍

Epidemiology

2
Infectious versus noninfectious aortitis distribution
In a French multicenter comparison, infectious aortitis accounted for about one-third of included aortitis cases and had distinct microbiologic and aneurysm patterns.
microbial etiology abdominal aortic involvement aneurysm at presentation
Show evidence (1 reference)
DOI:10.1093/cid/ciac560 SUPPORT Human Clinical
"One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
Quantifies infectious aortitis frequency and key organisms in a mixed infectious/noninfectious cohort.
G-CSF-induced aortitis case-review profile
The published case-review dataset is enriched for older women and oncology patients, with pegfilgrastim the most frequently implicated G-CSF agent. Case literature also suggests recurrence can occur after switching between short-acting G-CSF products in a genetically susceptible patient.
G-CSF exposure cancer chemotherapy pegfilgrastim exposure HLA-B52 susceptibility signal
Show evidence (2 references)
DOI:10.3389/fphar.2024.1487501 SUPPORT Human Clinical
"A total of 72 patients were enrolled, including 14 males and 58 females"
Summarizes the demographic profile of reported G-CSF-associated aortitis cases.
PMID:38521841 SUPPORT Human Clinical
"The patient possessed human leukocyte antigen B52, which has been implicated in Takayasu arteritis."
This case report supports an HLA-B52 susceptibility signal in G-CSF-associated aortitis, but it is single-patient evidence.
🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Aortitis:

Aortic or retroperitoneal sarcoma
Overlapping Features A primary aortic or adjacent retroperitoneal malignancy can produce pain, constitutional symptoms, and periaortic inflammatory change that resembles infectious or immune-mediated aortitis.
Distinguishing Features
  • Progressive symptoms or imaging abnormalities despite appropriate antimicrobial or immunosuppressive therapy.
  • A mass-like or atypical periaortic process that warrants tissue diagnosis when safely feasible.
Show evidence (1 reference)
PMID:41852766 SUPPORT Human Clinical
"Primary retroperitoneal aortic sarcoma is an exceptionally rare malignancy and may closely mimic inflammatory or infectious aortitis on clinical assessment and imaging."
A 2026 case report directly supports sarcoma as an uncommon but consequential mimic.
📊

Related Datasets

1
Spatial gene expression profiling of aortitis samples. geo:GSE306150
10X Xenium profiling of ascending aorta samples isolated from subjects with aortitis.
human SPATIAL TRANSCRIPTOMICS n=10
PMID:41948935
Identified by GEO DataSets index search for Aortitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

2
NCT03725202 PHASE_III COMPLETED
SELECT-GCA randomized participants with giant cell arteritis to upadacitinib plus a 26-week glucocorticoid taper or placebo plus a 52-week taper. It is relevant to an important etiology of aortitis but did not establish an aortitis-specific structural or imaging benefit.
Show evidence (1 reference)
clinicaltrials:NCT03725202 SUPPORT Human Clinical
"The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week corticosteroid (CS) taper regimen compared to placebo in combination with a 52-week CS taper regimen, as measured by the proportion of participants in sustained remission at Week 52"
Documents the completed phase III trial design and primary remission objective.
NCT06271018 NOT_APPLICABLE RECRUITING
TILT is a prospective French multicenter observational study of biosimilar tocilizumab plus short-course glucocorticoids in GCA with active aortitis, designed to evaluate vessel inflammation and damage by modern imaging. Its results were not yet available at the review cutoff.
Target Phenotypes: Aortitis HP:6001461 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Aortitis (HP:6001461). HP:6001461 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT06271018 SUPPORT Human Clinical
"This is a french multicenter observational study assessing safety and efficacy of biosimilar of Tocilizumab in Giant Cell Arteritis (GCA) with active aortitis, including 14 reference centers"
Establishes the aortitis-specific observational study scope; no outcome claim is made.
🐁

Animal Models

1
Mouse (Mus musculus)
Human temporal arteries with giant-cell arteritis remain inflamed after engraftment into SCID mice, enabling in-vivo study of vascular immune persistence and glucocorticoid response. The model uses temporal artery, not aorta, and does not reproduce systemic disease or chronic aortic remodeling and aneurysm formation.
Persistent human arterial inflammation Cytokine expression after glucocorticoid treatment
Species
Mouse (Mus musculus)
Background
SCID mouse bearing a human temporal-artery xenograft
Show evidence (1 reference)
PMID:9185506 SUPPORT Model Organism
"GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo."
Supports model validity for persistent human arterial inflammation while the description states its aortic limitations.
{ }

Source YAML

click to show 
name: Aortitis
creation_date: "2026-05-06T03:09:08Z"
description: >-
  Aortitis is inflammation of the aortic wall, spanning noninfectious
  large-vessel vasculitis, clinically isolated surgical-pathology aortitis,
  infectious aortitis, and drug-induced forms such as G-CSF-associated
  aortitis. The shared disease axis is aortic wall inflammation with risk for
  aneurysm, dissection, stenotic or occlusive disease, ischemic complications,
  and aortic valve involvement, but the required management differs sharply by
  etiology.
category: Complex
disease_term:
  preferred_term: aortitis
  term:
    id: MONDO:0006656
    label: aortitis
parents:
- Vascular disorder
- Vasculitis
- Inflammatory disorder
synonyms:
- Aorta inflammation
- Inflammation of aorta
- Aortic wall inflammation
review_notes: >-
  Publication-readiness review completed through 2026-08-05. A focused D2P
  audit returned six medium-priority local-phenotype suggestions. Aortitis was
  retained as the defining phenotype rather than linked causally to itself;
  elevated CRP, ESR, and serum IgG4 were modeled as observational readouts
  rather than causal intermediates; and fever and aortic regurgitation were left without
  pathograph edges because the available evidence establishes presentation or
  co-occurrence, not a direct causal step. No disorder-level gene assertion was
  added: reported HLA and other susceptibility signals are specific to
  etiologic diseases such as GCA or Takayasu arteritis and do not define this
  heterogeneous umbrella syndrome. This avoids false gene-pathway connectivity.
  The top-level references list is intentionally empty: interpreted claims and
  provenance are attached directly to the relevant objects, and automated
  backfill should not restore citation-only findings.
has_subtypes:
- name: Clinically isolated aortitis
  description: >-
    Histology-confirmed aortitis without known systemic inflammatory or
    infectious disease; many cases are discovered incidentally during aortic
    surgery.
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The prevalence of aortitis was 10.6% (n = 57), of which 75% were clinically isolated."
    explanation: >-
      This surgical cohort identifies clinically isolated aortitis as the
      majority subtype among histology-confirmed aortitis cases.
- name: Large-vessel vasculitis-associated aortitis
  description: >-
    Aortitis associated with giant cell arteritis, Takayasu arteritis, or other
    large- and variable-vessel vasculitides.
  evidence:
  - reference: DOI:10.3390/jcm13216364
    reference_title: "Imaging in Large Vessel Vasculitis-A Narrative Review"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Large vessel vasculitis (LVV), particularly giant cell arteritis (GCA) and Takayasu arteritis (TAK), has garnered attention due to its significant morbidity and mortality."
    explanation: >-
      This review anchors GCA and Takayasu arteritis as major large-vessel
      vasculitis contexts relevant to aortitis.
- name: Infectious aortitis
  description: >-
    Aortitis caused by microbial infection of the aortic wall, often presenting
    with aneurysm or structural aortic abnormalities and requiring urgent
    antimicrobial and vascular-surgery evaluation.
  evidence:
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
    explanation: >-
      This multicenter aortitis cohort identifies infectious aortitis cases and
      their causative organisms.
- name: G-CSF-associated drug-induced aortitis
  description: >-
    A rare adverse event after granulocyte-colony stimulating factor exposure,
    most often reported in oncology supportive-care settings and occasionally in
    healthy stem-cell donors.
  evidence:
  - reference: DOI:10.3389/fphar.2024.1487501
    reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recombinant human granulocyte-colony stimulating factors (G-CSF)-induced aortitis is a rare but particularly serious adverse event, commonly seen in cancer patients undergoing chemotherapy."
    explanation: >-
      This literature review supports G-CSF exposure as a drug-induced aortitis
      subtype, especially in chemotherapy care.
- name: IgG4-related aortitis/periaortitis
  description: >-
    Aortitis or periaortitis occurring in the context of IgG4-related disease,
    characterized by IgG4-bearing plasma-cell infiltration and fibrotic
    inflammation that predominantly affects the abdominal aorta and iliac
    arteries.
  evidence:
  - reference: DOI:10.3389/fimmu.2025.1625456
    reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
    explanation: >-
      The review defines IgG4-related disease by IgG4-bearing plasma-cell
      infiltration and fibrotic inflammation.
  - reference: DOI:10.3389/fimmu.2025.1625456
    reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "IgG4-related aortitis/periaortitis and periarteritis (IgG4-related PAO/PA) predominantly affect the abdominal aorta and iliac arteries, with a higher prevalence in elderly males."
    explanation: >-
      This directly supports IgG4-related aortitis/periaortitis as a distinct
      vascular manifestation.
prevalence:
- population: Single-center major aortic surgery cohort with high histology sampling
  percentage: 10.6%
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The prevalence of aortitis was 10.6% (n = 57), of which 75% were clinically isolated."
    explanation: >-
      Provides the observed prevalence of histology-confirmed aortitis in a
      high-sampling surgical cohort.
epidemiology:
- name: Infectious versus noninfectious aortitis distribution
  description: >-
    In a French multicenter comparison, infectious aortitis accounted for about
    one-third of included aortitis cases and had distinct microbiologic and
    aneurysm patterns.
  factors:
  - microbial etiology
  - abdominal aortic involvement
  - aneurysm at presentation
  evidence:
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
    explanation: >-
      Quantifies infectious aortitis frequency and key organisms in a mixed
      infectious/noninfectious cohort.
- name: G-CSF-induced aortitis case-review profile
  description: >-
    The published case-review dataset is enriched for older women and oncology
    patients, with pegfilgrastim the most frequently implicated G-CSF agent.
    Case literature also suggests recurrence can occur after switching between
    short-acting G-CSF products in a genetically susceptible patient.
  factors:
  - G-CSF exposure
  - cancer chemotherapy
  - pegfilgrastim exposure
  - HLA-B52 susceptibility signal
  evidence:
  - reference: DOI:10.3389/fphar.2024.1487501
    reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A total of 72 patients were enrolled, including 14 males and 58 females"
    explanation: >-
      Summarizes the demographic profile of reported G-CSF-associated aortitis
      cases.
  - reference: PMID:38521841
    reference_title: Aortitis after switching short-acting granulocyte colony-stimulating factors in a lymphoma patient with HLA-B52.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The patient possessed human leukocyte antigen B52, which has been implicated
      in Takayasu arteritis.
    explanation: This case report supports an HLA-B52 susceptibility signal in G-CSF-associated aortitis, but it is single-patient evidence.
pathophysiology:
- name: Immune-mediated aortic wall inflammation in large-vessel vasculitis
  description: >-
    Large-vessel vasculitis-associated aortitis involves immune-mediated
    inflammation of the vascular wall, including inflammatory cell accumulation
    in aortic tissue in Takayasu arteritis.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: granulocyte
    term:
      id: CL:0000094
      label: granulocyte
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  - preferred_term: smooth muscle cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: adaptive immune response
    modifier: ABNORMAL
    term:
      id: GO:0002250
      label: adaptive immune response
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  evidence:
  - reference: DOI:10.3390/jcm13216364
    reference_title: "Imaging in Large Vessel Vasculitis-A Narrative Review"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Both conditions involve immune-mediated inflammation of the vascular wall, despite differing in epidemiology and presentation."
    explanation: >-
      Supports immune-mediated vascular-wall inflammation as a shared mechanism
      in the GCA/TAK large-vessel vasculitis context.
  - reference: DOI:10.1177/000331970005100705
    reference_title: "Accumulation of Lymphocytes, Dendritic Cells, and Granulocytes in the Aortic Wall Affected by Takayasu's Disease"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CD68 (macrophages), CD15 (granulocytes), von Willebrand factor (endothelial cells), and alpha-smooth muscle actin (smooth muscle cells)."
    explanation: >-
      Directly supports macrophage and granulocyte involvement in affected
      aortic wall tissue in Takayasu arteritis.
  - reference: DOI:10.1177/000331970005100705
    reference_title: "Accumulation of Lymphocytes, Dendritic Cells, and Granulocytes in the Aortic Wall Affected by Takayasu's Disease"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "(endothelial cells), and alpha-smooth muscle actin (smooth muscle cells)."
    explanation: >-
      Supports endothelial-cell and smooth-muscle-cell assessment in affected
      aortic wall tissue.
  downstream:
  - target: Aortic wall structural remodeling
    description: >-
      Persistent vascular inflammation contributes to later remodeling and
      structural complications such as aneurysm, dissection, or ischemia.
    evidence:
    - reference: PMID:41948935
      reference_title: Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Single-cell spatial profiling revealed aortic wall remodeling in the GCA
        aortas, highlighting substantial phenotypic modulation in stromal cells,
        including vascular smooth muscle cells (SMCs) and fibroblasts.
      explanation: Human aortic-tissue profiling directly links giant-cell aortitis with stromal remodeling.
  - target: Tenascin-C and IL-6 inflammatory persistence
    description: Immune-mediated giant-cell aortitis is associated with lesion-localized tenascin-C accumulation and stromal inflammatory modulation.
    evidence:
    - reference: PMID:41948935
      reference_title: Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Specifically, we observed the expansion of stromal cells expressing
        Tenascin-C (TNC) mRNA and spatially refined TNC accumulation in lesion areas.
      explanation: Supports TNC accumulation as a downstream lesion-associated feature in human giant-cell aortitis tissue.
- name: Infectious aortic wall infection
  description: >-
    Infectious aortitis is initiated by microbial infection of native aortic
    tissue. Acute reported causes include Salmonella species, Staphylococcus
    species, Streptococcus pneumoniae, and other streptococci; syphilitic and
    tuberculous forms may be subacute. Infection may produce wall thickening or
    aneurysmal distortion and a higher-mortality phenotype than noninfectious
    aortitis.
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  evidence:
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "One hundred eighty-three patients were included. Of these, 66 had IA (36.1%); the causative organism was Enterobacterales and streptococci in 18.2% each"
    explanation: >-
      Identifies causative organisms in infectious aortitis and supports
      microbial infection as the upstream etiology.
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P &lt; .001), especially located in the abdominal aorta (69.7% vs 23.1%, P &lt; .001)."
    explanation: >-
      Links infectious aortitis to aneurysmal aortic injury more strongly than
      noninfectious aortitis in the comparison cohort.
  - reference: PMID:26775836
    reference_title: "[Infectious aortitis caused by Streptococcus pneumoniae]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The syphilitic or tubercular forms can be subacute. When it is caused by
      Salmonella sp., Staphylococcus sp. or Streptococcus pneumoniae, the aortitis
      is acute with alarming symptoms.
    explanation: Names representative acute microbial causes and distinguishes subacute syphilitic or tuberculous disease.
  downstream:
  - target: Aortic aneurysm
    description: Infectious wall injury commonly presents with aneurysmal aortic disease.
    evidence:
    - reference: DOI:10.1093/cid/ciac560
      reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P &lt; .001), especially located in the abdominal aorta (69.7% vs 23.1%, P &lt; .001)."
      explanation: >-
        Provides cohort-level evidence that infectious aortitis is strongly
        associated with aneurysm.
- name: G-CSF-associated aortic inflammation
  description: >-
    Exogenous G-CSF exposure can trigger aortitis as a serious adverse event,
    most often detected by CT in the aortic arch and branch vessels.
  biological_processes:
  - preferred_term: cytokine-mediated signaling pathway
    modifier: ABNORMAL
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  triggers:
  - preferred_term: granulocyte-colony stimulating factor exposure
  evidence:
  - reference: DOI:10.3389/fphar.2024.1487501
    reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
    explanation: >-
      Identifies G-CSF exposure, particularly pegfilgrastim, as the most common
      trigger in the case-review dataset.
  - reference: PMID:38521841
    reference_title: Aortitis after switching short-acting granulocyte colony-stimulating factors in a lymphoma patient with HLA-B52.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      switching from one short-acting G-CSF to another does not prevent recurrence
      of G-CSF-associated aortitis.
    explanation: The case supports recurrence after switching short-acting G-CSF preparations and helps explain why re-exposure should be treated cautiously.
  downstream:
  - target: Aortic wall structural remodeling
    description: Rare reported G-CSF-associated cases progressed to aneurysm or dissection.
    evidence:
    - reference: DOI:10.3389/fphar.2024.1487501
      reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        most cases, but one case led to aortic aneurysm, and two case led
        aortic dissection.
      explanation: Supports uncommon structural complications in a 72-case literature review; the edge is partial because most cases did not progress.
- name: IgG4-related plasma-cell fibrotic vascular inflammation
  description: >-
    IgG4-related aortitis/periaortitis involves chronic fibrotic inflammation
    with IgG4-bearing plasma-cell infiltration in large-vessel tissue.
  cell_types:
  - preferred_term: plasma cell
    term:
      id: CL:0000786
      label: plasma cell
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  evidence:
  - reference: DOI:10.3389/fimmu.2025.1625456
    reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
    explanation: >-
      Supports a fibrotic inflammatory and IgG4-bearing plasma-cell mechanism
      for IgG4-related large-vessel disease.
  downstream:
  - target: Aortic wall structural remodeling
    description: Fibrotic inflammatory large-vessel disease can contribute to aneurysm, dissection, or rupture.
    evidence:
    - reference: DOI:10.3389/fimmu.2025.1625456
      reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
      explanation: Supports fibrotic inflammation but does not by itself establish a specific structural complication.
- name: Tenascin-C and IL-6 inflammatory persistence
  description: >-
    In resected giant-cell, clinically isolated, and IgG4-related aortitis
    specimens, tenascin-C accumulated in lesions and stromal cells showed
    phenotypic modulation. Primary human smooth-muscle-cell experiments support
    a TNC-TLR4/NF-kappaB-IL-6-STAT3 inflammatory loop; this mechanistic component
    is experimental and not yet a validated therapeutic biomarker.
  cell_types:
  - preferred_term: smooth muscle cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: cytokine-mediated signaling pathway
    modifier: INCREASED
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  evidence:
  - reference: PMID:41948935
    reference_title: Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We confirmed these findings histologically using diseased aortas resected
      from individuals with giant cell arteritis and clinically isolated aortitis.
    explanation: Confirms lesion-associated findings in human resected aortas.
  - reference: PMID:41948935
    reference_title: Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Mechanistically, our data suggest that TNC promotes a proinflammatory
      phenotype in primary human SMCs, elevating IL-6 levels partially through
      the TLR4/NF-κB pathway. IL-6 signaling propagates the proinflammatory loop
      by activating STAT3.
    explanation: Supports the proposed signaling loop in primary human smooth-muscle-cell experiments.
  downstream:
  - target: Aortic wall structural remodeling
    description: Lesion-associated stromal modulation accompanies aortic wall remodeling.
    evidence:
    - reference: PMID:41948935
      reference_title: Spatially controlled tenascin-C accumulation contributes to inflammatory disease persistence in giant cell aortitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Single-cell spatial profiling revealed aortic wall remodeling in the GCA
        aortas, highlighting substantial phenotypic modulation in stromal cells,
        including vascular smooth muscle cells (SMCs) and fibroblasts.
      explanation: Supports an association between stromal modulation and remodeling in affected human aortas.
- name: Aortic wall structural remodeling
  description: >-
    Inflammatory injury can weaken and remodel the aortic wall, producing
    aneurysm or dissection and driving the need for long-term aortic follow-up.
  cell_types:
  - preferred_term: smooth muscle cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  locations:
  - preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
    explanation: >-
      Directly links aortic inflammation to the principal structural
      complications of aneurysm and dissection.
  downstream:
  - target: Aortic aneurysm
    description: Aortic wall remodeling can present as aneurysmal dilation.
    evidence:
    - reference: DOI:10.3390/jcdd11120405
      reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
      explanation: Supports aneurysm as a structural complication of aortitis.
  - target: Aortic dissection
    description: Weakened and inflamed aortic wall can dissect.
    evidence:
    - reference: DOI:10.3390/jcdd11120405
      reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
      explanation: Supports dissection as a structural complication of aortitis.
phenotypes:
- category: Cardiovascular
  name: Aortitis
  diagnostic: true
  description: Inflammation of the aortic wall is the defining feature of aortitis.
  phenotype_term:
    preferred_term: Aortitis
    term:
      id: HP:6001461
      label: Aortitis
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
    explanation: The abstract defines aortitis as inflammation of the aorta.
- category: Cardiovascular
  name: Aortic aneurysm
  description: Aortic wall inflammation can weaken the vessel wall and contribute to aneurysmal dilation.
  phenotype_term:
    preferred_term: Aortic aneurysm
    term:
      id: HP:0004942
      label: Aortic aneurysm
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
    explanation: The abstract directly names aneurysm as a complication of aortitis.
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "IA was more frequently associated with aortic aneurysms compared with NIA (78.8% vs 17.6%, P &lt; .001), especially located in the abdominal aorta (69.7% vs 23.1%, P &lt; .001)."
    explanation: >-
      The infectious/noninfectious comparison shows a strong association between
      infectious aortitis and aortic aneurysm.
- category: Cardiovascular
  name: Aortic dissection
  description: Severe inflammatory weakening of the aorta can predispose to dissection.
  phenotype_term:
    preferred_term: Aortic dissection
    term:
      id: HP:0002647
      label: Aortic dissection
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Aortitis, defined as inflammation of the aorta, can lead to aneurysms and dissections."
    explanation: The abstract directly names dissection as a complication of aortitis.
- category: Cardiovascular
  name: Aortic regurgitation
  description: Aortic root or ascending aortic inflammation can impair aortic valve competence.
  phenotype_term:
    preferred_term: Aortic regurgitation
    term:
      id: HP:0001659
      label: Aortic regurgitation
  evidence:
  - reference: DOI:10.62186/001c.146456
    reference_title: "Stroke, Aortic Regurgitation and Aortic Aneurysm in Younger Female: Case of Giant Cell Aortitis and Discussion"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Due to severe aortic regurgitation limiting her activity and aortic root aneurysm"
    explanation: >-
      This case report links giant cell aortitis with severe aortic
      regurgitation and aortic root aneurysm.
- category: Constitutional
  name: Fever
  description: >-
    Fever is a common presentation in symptomatic G-CSF-associated aortitis and
    can trigger evaluation for drug-induced aortic inflammation.
  subtype: G-CSF-associated drug-induced aortitis
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:40272133
    reference_title: Aortitis triggered by granulocyte-colony stimulating factor.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of G-CSF-induced aortitis should be considered in patients with fever after G-CSF treatment, particularly if adequate antibiotic treatment does not lead to improvement."
    explanation: >-
      The case report interpretation explicitly links fever after G-CSF
      exposure to consideration of G-CSF-induced aortitis.
  - reference: PMID:34448091
    reference_title: "Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "If a patient develops a persistent high fever of unknown origin after pegfilgrastim administration, drug-induced aortitis should be considered during investigations for causes of fever."
    explanation: >-
      The case-report conclusion supports persistent high fever as a key
      clinical clue for pegfilgrastim-induced aortitis.
- category: Laboratory
  name: Elevated C-reactive protein
  description: >-
    C-reactive protein may be markedly elevated in drug-induced aortitis and is
    used clinically as an inflammatory activity marker.
  subtype: G-CSF-associated drug-induced aortitis
  phenotype_term:
    preferred_term: Elevated circulating C-reactive protein concentration
    term:
      id: HP:0011227
      label: Elevated circulating C-reactive protein concentration
  reports_on:
  - target: G-CSF-associated aortic inflammation
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Serum C-reactive protein reflecting systemic inflammatory activity of aortic inflammation.
    evidence:
    - reference: PMID:40272133
      reference_title: Aortitis triggered by granulocyte-colony stimulating factor.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "After four days, C-reactive protein (CRP) had increased from 104 to 331, but the patient's condition was largely unchanged."
      explanation: Supports CRP as a positive observational readout during G-CSF-associated aortitis.
  evidence:
  - reference: PMID:40272133
    reference_title: Aortitis triggered by granulocyte-colony stimulating factor.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "After four days, C-reactive protein (CRP) had increased from 104 to 331, but the patient's condition was largely unchanged."
    explanation: >-
      The case report documents marked CRP increase during G-CSF-associated
      aortitis evaluation.
  - reference: PMID:34448091
    reference_title: "Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Therefore, C-reactive protein (CRP) is currently used to assess disease activity in clinical practice."
    explanation: >-
      The full-text case report notes CRP use for assessing G-CSF-associated
      aortitis activity.
- category: Laboratory
  name: Elevated erythrocyte sedimentation rate
  description: >-
    Elevated erythrocyte sedimentation rate can accompany large-vessel
    vasculitis-associated aortitis presentations and supports inflammatory
    activity assessment.
  subtype: Large-vessel vasculitis-associated aortitis
  phenotype_term:
    preferred_term: Elevated erythrocyte sedimentation rate
    term:
      id: HP:0003565
      label: Elevated erythrocyte sedimentation rate
  reports_on:
  - target: Immune-mediated aortic wall inflammation in large-vessel vasculitis
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: ESR is a nonspecific systemic inflammatory readout and does not establish aortic-wall activity by itself.
    evidence:
    - reference: PMID:36843728
      reference_title: "From Temporal Cell Arteritis to Giant Cell Aortitis Presenting as a Constitutional Syndrome: A Case Report."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated, and he also had inflammatory anemia with a hemoglobin of 11.7 g/L."
      explanation: Supports elevated ESR as a readout in a giant-cell-aortitis presentation, with single-case limitations.
  evidence:
  - reference: PMID:36843728
    reference_title: "From Temporal Cell Arteritis to Giant Cell Aortitis Presenting as a Constitutional Syndrome: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated, and he also had inflammatory anemia with a hemoglobin of 11.7 g/L."
    explanation: >-
      This giant-cell-aortitis case report documents elevated ESR and CRP in the
      inflammatory presentation.
- category: Laboratory
  name: Increased circulating IgG4 level
  description: >-
    Elevated serum IgG4 can accompany IgG4-related aortitis/periaortitis but is
    not independently diagnostic of vascular involvement.
  subtype: IgG4-related aortitis/periaortitis
  phenotype_term:
    preferred_term: Increased circulating IgG4 level
    modifier: INCREASED
    term:
      id: HP:0032300
      label: Increased circulating IgG4 level
  reports_on:
  - target: IgG4-related plasma-cell fibrotic vascular inflammation
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Serum IgG4 is a nonspecific laboratory readout in the IgG4-related subtype.
    evidence:
    - reference: DOI:10.3389/fimmu.2025.1625456
      reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
      explanation: Supports elevated serum IgG4 as a readout of IgG4-related disease.
  evidence:
  - reference: DOI:10.3389/fimmu.2025.1625456
    reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory condition characterized by elevated serum IgG4 levels and the infiltration of IgG4-bearing plasma cells in affected organs."
    explanation: Supports elevated serum IgG4 in the parent IgG4-related disease while preserving its nonspecificity for aortitis.
histopathology:
- name: Aortic wall inflammatory infiltrates
  finding_term:
    preferred_term: Aortic wall inflammatory infiltrate
    term:
      id: NCIT:C35978
      label: Inflammatory Infiltrate
  description: >-
    Aortitis can show inflammatory infiltrates in the aortic wall, with
    lymphocytes, dendritic cells, macrophages, granulocytes, endothelial cells,
    and smooth muscle cells characterized in Takayasu aortic tissue.
  diagnostic: true
  context: Large-vessel vasculitis-associated aortitis
  evidence:
  - reference: DOI:10.1177/000331970005100705
    reference_title: "Accumulation of Lymphocytes, Dendritic Cells, and Granulocytes in the Aortic Wall Affected by Takayasu's Disease"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All specimens showed distinctive histologic features of Takayasu's arteritis and contained inflammatory infiltrates"
    explanation: >-
      Histologic inflammatory infiltrates in aortic wall tissue support this
      microscopic aortitis feature.
- name: Histology-confirmed clinically isolated aortitis
  description: >-
    Clinically isolated aortitis is often diagnosed through intra-operative
    aortic sampling rather than through preoperative clinical symptoms.
  diagnostic: true
  context: Major aortic surgery
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
    explanation: >-
      Supports intra-operative histologic sampling as a key diagnostic route for
      clinically isolated aortitis.
imaging_findings:
- name: Aortic wall thickening on cross-sectional imaging
  modality: CT
  imaging_finding_term:
    preferred_term: Aortic wall thickening
  located_in:
    preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  spatial_extent: DIFFUSE
  diagnostic: false
  description: >-
    Circumferential aortic-wall thickening on CTA or MRI supports active
    inflammatory aortic disease but is not pathognomonic and must be interpreted
    with clinical, microbiologic, and other imaging evidence.
  notes: No sufficiently specific HP or NCIT term was identified at review; ontology term request is needed.
  evidence:
  - reference: DOI:10.3390/jcm13216364
    reference_title: "Imaging in Large Vessel Vasculitis-A Narrative Review"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
    explanation: Supports wall thickening as a suggestive, not pathognomonic, large-vessel imaging feature.
- name: Increased aortic FDG uptake on PET/CT
  modality: PET
  imaging_finding_term:
    preferred_term: Increased aortic fluorodeoxyglucose uptake
  located_in:
    preferred_term: aorta
    term:
      id: UBERON:0000947
      label: aorta
  spatial_extent: DIFFUSE
  diagnostic: false
  description: >-
    Increased 18F-FDG uptake in the aorta with or without major branches is used
    to assess inflammatory activity and treatment response, but uptake is
    nonspecific and imaging normalization may lag behind clinical remission.
  notes: No sufficiently specific HP or NCIT term was identified at review; ontology term request is needed.
  evidence:
  - reference: PMID:41186891
    reference_title: "Treatment and evolution of 134 patients with aortitis and periaortitis: experience of a third-level university hospital."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The main diagnostic method was the positron emission tomography (PET),
      showing a non-specific increase in 18F-FDG uptake of the aorta with/without
      its major branches.
    explanation: Supports the finding and explicitly preserves its nonspecificity.
environmental:
- name: Granulocyte-colony stimulating factor exposure
  influences_mechanisms:
  - target: G-CSF-associated aortic inflammation
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      The node is named for this drug, so the exposure is the node's own
      content rather than something inferred onto it, and direct is the honest
      link type for a drug-induced inflammation with no intervening disease.
      The strongest item is the second: patients re-exposed to the drug
      developed the aortitis again, and the review concludes that neither
      repeated use nor a change of preparation rules out recurrence.
      Recurrence on re-exposure is the classic argument for drug causation and
      is what lifts this link above an association. Note for anyone
      re-checking this entry that the reference is a DOI, and the reference
      validator skips DOI-prefixed snippets, so every quote here was verified
      against the cached record by hand.
    evidence:
    - reference: DOI:10.3389/fphar.2024.1487501
      reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "(G-CSF)-induced aortitis is a rare but particularly serious adverse event, commonly seen in cancer patients undergoing chemotherapy"
      explanation: >-
        States drug-induced aortitis as an adverse event of this drug rather
        than assuming it, which is the claim this edge makes.
    - reference: DOI:10.3389/fphar.2024.1487501
      reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This indicated that patients with a history of G-CSF-induced aortitis, whether through repeated use or changes in dosage form, cannot rule out the possibility of recurrent G-CSF-induced aortitis"
      explanation: >-
        The review's conclusion from its re-administration cases: the aortitis
        returns when the drug does, and switching preparation does not prevent
        it. Recurrence on re-exposure is the strongest causal design available
        for a drug, and it is what this link rests on. Two limits belong with
        it rather than after it: the authors qualify this very sentence by
        noting that reporting bias means the possibility still needs further
        validation, and the underlying numbers are small, three
        re-administrations of the same preparation plus two switches.
    - reference: DOI:10.3389/fphar.2024.1487501
      reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
      explanation: >-
        Names pegfilgrastim as the G-CSF most frequently associated with
        aortitis. It settles which agent within an association it takes as
        given, so it supports the edge by assuming it rather than by showing
        it, and it stays partial for that reason now that the two items above
        carry the claim directly.
  presence: Positive
  description: >-
    G-CSF exposure, particularly pegfilgrastim in reported cases, can trigger
    drug-induced aortitis.
  evidence:
  - reference: DOI:10.3389/fphar.2024.1487501
    reference_title: "Literature review analysis of aortitis induced by granulocyte-colony stimulating factor"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The G-CSF type with the highest frequency of occurrence of aortitis is pegfilgrastim."
    explanation: >-
      Identifies pegfilgrastim as the most frequently reported G-CSF exposure in
      G-CSF-associated aortitis.
- name: Current tobacco smoking
  influences_mechanisms:
  - target: Aortic wall structural remodeling
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      The target was forced by the graph as much as chosen: every
      inflammatory node in this entry is etiology-specific, naming
      large-vessel vasculitis, infection, G-CSF or IgG4, so wall remodeling is
      the only etiology-agnostic node available to an exposure that belongs to
      none of those arms. The cited regression associates smoking with
      aortitis as a whole and names no mechanism, so nothing in the evidence
      points anywhere in particular; remodeling is where a chronic inhaled
      exposure is understood to land. Intermediates unknown for the
      same reason. This is the weakest link in the tranche and is graded to
      say so.
    evidence:
    - reference: DOI:10.3390/jcdd11120405
      reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Multivariate logistic regression identified increased age, female sex, current smoking, and other inflammatory diseases as significantly associated with aortitis"
      explanation: >-
        A multivariate regression identifying current smoking, along with age,
        female sex and other inflammatory diseases, as significantly
        associated with aortitis. It establishes that smokers are
        over-represented and says nothing about the aortic wall.
  presence: Positive
  description: >-
    Current smoking was associated with histology-confirmed aortitis in a major
    aortic surgery cohort.
  exposure_term:
    preferred_term: exposure to tobacco smoking
    term:
      id: ECTO:6000029
      label: exposure to tobacco smoking
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Multivariate logistic regression identified increased age, female sex, current smoking, and other inflammatory diseases as significantly associated with aortitis"
    explanation: >-
      Supports current smoking as a clinical risk association in the surgical
      aortitis cohort.
diagnosis:
- name: Histologic aortic wall assessment
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  description: >-
    Intra-operative aortic sampling can diagnose clinically isolated aortitis
    that may be missed clinically.
  results: Aortic wall inflammation on histology supports the diagnosis.
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
    explanation: >-
      Supports histologic assessment as a diagnostic approach in surgical
      aortitis and clinically isolated aortitis.
- name: Large-vessel vascular imaging
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  description: >-
    CTA, ultrasound, MRI, and FDG-PET are used to detect large-vessel vasculitis
    activity, wall thickening, and aortic or branch-vessel involvement.
  results: Vessel-wall thickening or FDG uptake supports active vascular inflammation.
  evidence:
  - reference: DOI:10.3390/jcm13216364
    reference_title: "Imaging in Large Vessel Vasculitis-A Narrative Review"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
    explanation: >-
      Supports vascular imaging as a diagnostic method for large-vessel
      vasculitis-associated aortitis.
  - reference: DOI:10.1136/rmdopen-2023-003379
    reference_title: "Imaging in diagnosis, monitoring and outcome prediction of large vessel vasculitis: a systematic literature review and meta-analysis informing the 2023 update of the EULAR recommendations"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ultrasound, MRI and FDG-PET revealed a good performance for the diagnosis of GCA."
    explanation: >-
      Supports ultrasound, MRI, and FDG-PET as evidence-backed imaging tools in
      giant-cell-arteritis large-vessel disease.
- name: Infectious versus noninfectious etiology assessment
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  description: >-
    Evaluation should distinguish infectious aortitis from noninfectious
    aortitis because treatment and mortality risk differ.
  results: Microbiologic evidence and aortic imaging pattern help classify etiology.
  evidence:
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Determining the etiology of aortitis is often challenging, in particular to distinguish infectious aortitis (IA) and noninfectious aortitis (NIA)."
    explanation: >-
      Supports explicit infectious/noninfectious etiologic assessment during
      aortitis diagnosis.
  - reference: DOI:10.3390/jcm13216364
    reference_title: "Imaging in Large Vessel Vasculitis-A Narrative Review"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Vascular imaging, including computed tomography angiography (CTA), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT), is key in diagnosing vasculitis, revealing vessel wall thickening and other suggestive features."
    explanation: >-
      Supports vascular imaging as a central diagnostic tool when evaluating
      aortitis and large-vessel vasculitis.
differential_diagnoses:
- name: Aortic or retroperitoneal sarcoma
  description: >-
    A primary aortic or adjacent retroperitoneal malignancy can produce pain,
    constitutional symptoms, and periaortic inflammatory change that resembles
    infectious or immune-mediated aortitis.
  distinguishing_features:
  - Progressive symptoms or imaging abnormalities despite appropriate antimicrobial or immunosuppressive therapy.
  - A mass-like or atypical periaortic process that warrants tissue diagnosis when safely feasible.
  evidence:
  - reference: PMID:41852766
    reference_title: "Aortic malignancy masquerading as infrarenal aortitis: A diagnostic challenge."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Primary retroperitoneal aortic sarcoma is an exceptionally rare malignancy
      and may closely mimic inflammatory or infectious aortitis on clinical
      assessment and imaging.
    explanation: A 2026 case report directly supports sarcoma as an uncommon but consequential mimic.
treatments:
- name: Glucocorticoid therapy for noninfectious aortitis
  description: >-
    Glucocorticoids are a first-line immunosuppressive treatment backbone for
    noninfectious large-vessel aortitis contexts, including giant cell arteritis
    and IgG4-related aortitis/periaortitis.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: glucocorticoid
      term:
        id: CHEBI:24261
        label: glucocorticoid
    - preferred_term: prednisolone
      term:
        id: CHEBI:8378
        label: prednisolone
  evidence:
  - reference: DOI:10.1186/s13063-024-07905-4
    reference_title: "The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates."
    explanation: >-
      Giant cell arteritis is a major large-vessel vasculitis context for
      aortitis, and this trial protocol identifies glucocorticoids as standard
      treatment.
  - reference: PMID:36843728
    reference_title: "From Temporal Cell Arteritis to Giant Cell Aortitis Presenting as a Constitutional Syndrome: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment with high-dose steroids should be initiated as soon as possible to rapidly control the inflammatory symptoms and prevent ischemic complications"
    explanation: >-
      This giant-cell-arteritis/aortitis case report supports high-dose steroid
      treatment for inflammatory large-vessel disease.
  - reference: DOI:10.3389/fimmu.2025.1625456
    reference_title: "Unraveling the complexity of IgG4-related aortitis and periarteritis: from pathogenesis to clinical practice"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Glucocorticoids (GCs) are the mainstay of treatment, often combined with immunosuppressants (IMs), while B- and T-cell-targeted therapies are under investigation."
    explanation: >-
      The IgG4-related aortitis review directly supports glucocorticoids as a
      mainstay treatment for IgG4-related aortitis/periaortitis.
  - reference: PMID:41186891
    reference_title: "Treatment and evolution of 134 patients with aortitis and periaortitis: experience of a third-level university hospital."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glucocorticoids are the first line of treatment in patients with non-infectious aortitis or periaortitis."
    explanation: Directly supports first-line use in a 134-patient referral-center cohort.
- name: Empiric antimicrobial therapy for infectious aortitis
  description: >-
    Infectious aortitis requires early antimicrobial therapy, initially empiric
    when microbiologic documentation is pending and then adapted to organism and
    susceptibility data.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: DOI:10.1093/cid/ciac560
    reference_title: "Retrospective Multicenter Study Comparing Infectious and Noninfectious Aortitis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Effective empiric antimicrobial therapy, initiated before any microbial documentation, was associated with a decreased mortality"
    explanation: >-
      Supports early empiric antimicrobial therapy as a mortality-associated
      protective intervention in infectious aortitis.
- name: Tocilizumab for LVV-associated aortitis contexts
  description: >-
    Tocilizumab may be used for large-vessel vasculitis phenotypes associated
    with aortitis, with clinical remission and glucocorticoid-sparing effects
    reported in LV-GCA and Takayasu arteritis cohorts.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: DOI:10.3390/sci7010012
    reference_title: "Tocilizumab in Extracranial Giant-Cell Arteritis and Takayasu Arteritis: A Multicentric Observational Comparative Study"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tocilizumab (TCZ) has demonstrated potential efficacy in managing large-vessel (LV) vasculitis such as giant-cell arteritis (GCA) and Takayasu arteritis (TAK)."
    explanation: >-
      Supports tocilizumab as a treatment option in the LVV contexts that can
      include aortitis.
  - reference: DOI:10.3390/sci7010012
    reference_title: "Tocilizumab in Extracranial Giant-Cell Arteritis and Takayasu Arteritis: A Multicentric Observational Comparative Study"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "complete imaging resolution was observed in only 18.9% of LV-GCA patients and 21.1% of TAK patients."
    explanation: >-
      The clinical benefit is tempered by incomplete imaging resolution,
      supporting a partial rather than complete effect on vascular inflammation.
  - reference: PMID:41531143
    reference_title: "Subcutaneous Versus Intravenous Tocilizumab in Aortitis Associated With Giant Cell Arteritis: Multicenter Study of 196 Patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In this real-world cohort of GCA-associated aortitis, SC TCZ showed
      slightly greater effectiveness than IV TCZ in achieving EULAR-defined remission,
      whereas no significant differences were observed between both routes regarding
      imaging remission.
    explanation: Supports route-specific comparative outcomes in GCA-associated aortitis without claiming superiority for imaging remission.
- name: Upadacitinib for giant-cell-arteritis contexts
  description: >-
    Upadacitinib is a JAK inhibitor with phase III evidence for giant cell
    arteritis, a major large-vessel vasculitis context that can include
    aortitis. Its long-term effect on aortic remodeling remains uncertain.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:40174237
    reference_title: "A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg - but
      not 7.5 mg - with a 26-week glucocorticoid taper showed efficacy superior
      to that of placebo with a 52-week glucocorticoid taper.
    explanation: The SELECT-GCA phase III trial supports upadacitinib efficacy in GCA, but not specifically aortic remodeling or aortitis endpoints.
- name: Specialist multidisciplinary follow-up and aortic surveillance
  description: >-
    Patients with aortitis require specialist follow-up because of increased
    re-intervention risk and late aortic complications.
  treatment_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Due to the increased re-intervention in aortitis, specialist multi-disciplinary follow-up and aortitis centres should be formed."
    explanation: >-
      Supports specialist multidisciplinary follow-up for aortitis after major
      aortic surgery.
  - reference: PMID:40099651
    reference_title: "Isolated aortitis - is it truly isolated? An approach to diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Surveillance of patients with IA with repeated clinical assessments and imaging
      is recommended.
    explanation: This review supports repeated clinical and imaging surveillance for isolated aortitis.
  - reference: PMID:41365838
    reference_title: "The influence of baseline aortitis on aortic dilation risk in GCA: a multicentre imaging study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Baseline aortic diameter was the strongest predictor of aortic expansion
      (β = 0.088; P = 0.006) and incident aortic dilation (adjusted hazard ratio
      3.9; 95% CI: 2.0, 7.3).
    explanation: Supports longitudinal dimension monitoring in a 157-patient multicenter GCA cohort.
progression:
- phase: Acute outcomes after open thoracic aortic aneurysm repair
  notes: >-
    In a United States administrative cohort of open thoracic aortic aneurysm
    repairs, a coded diagnosis of noninfectious aortitis was independently
    associated with worse in-hospital outcomes. This is a post-intervention,
    selected-population association rather than disease incidence or causality.
  evidence:
  - reference: PMID:42175556
    reference_title: Association of Non-infectious Aortitis With Acute Outcomes of Open Thoracic Aortic Aneurysm Repair.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Following multivariable adjustment, aortitis was independently associated
      with increased odds of in-hospital mortality (AOR: 1.45, 95% CI:
      1.14-1.84), major adverse cardiac and cerebrovascular events (AOR: 1.40,
      95% CI: 1.15-1.70), neurologic complications (AOR: 1.33, 95% CI:
      1.05-1.70), and nonhome discharge (AOR: 1.38, 95% CI: 1.19-1.60).
    explanation: >-
      Reports adjusted acute outcome associations in a national administrative
      cohort; it does not establish aortitis as the cause of each outcome.
- phase: Asymptomatic discovery during aortic surgery
  subtype: Clinically isolated aortitis
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intra-operative sampling is essential for diagnosis, with many cases presenting asymptomatically as clinically isolated aortitis."
    explanation: >-
      Supports asymptomatic surgical discovery as an important presentation mode
      for clinically isolated aortitis.
- phase: Re-intervention after aortitis-associated aortic surgery
  notes: Re-operation risk is higher in aortitis than in non-aortitis surgical comparators.
  evidence:
  - reference: DOI:10.3390/jcdd11120405
    reference_title: "Aortitis Increases the Risk of Surgical Complications and Re-Operations After Major Aortic Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The re-operation rate in aortitis was twice that of non-aortitis patients (17.5% vs. 9.4%, p = 0.054)."
    explanation: >-
      Quantifies higher post-surgical re-operation rates in the aortitis cohort.
- phase: Accelerated thoracic aortic aneurysm growth in inflammatory aortitis
  notes: >-
    A small retrospective matched study found faster preoperative aneurysm
    growth with histology-confirmed aortitis, especially clinically isolated
    aortitis; prospective validation is needed.
  evidence:
  - reference: PMID:42276733
    reference_title: Aortitis accelerates the growth rate of thoracic aortic aneurysms.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The mean growth rate was significantly higher in the aortitis group
      (0.177±0.01 mm/month; 2.12 mm/year) compared with controls
      (0.039±0.02 mm/month; 0.47 mm/year), representing a 4.5-fold acceleration
      (p<0.001).
    explanation: Supports an association with faster growth in 23 aortitis cases and 42 matched controls.
- phase: Discordant clinical and imaging remission
  notes: >-
    Clinical or laboratory improvement does not reliably imply normalization of
    vascular imaging, supporting multimodal longitudinal assessment.
  evidence:
  - reference: PMID:41186891
    reference_title: "Treatment and evolution of 134 patients with aortitis and periaortitis: experience of a third-level university hospital."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      After a mean follow-up of 39.2 ± 26.7 months, 72 patients (53.7%)
      experienced clinical remission, 64 (47.8%) complete remission and only 15
      (11.2%) imaging remission.
    explanation: Quantifies remission discordance in a single referral-center cohort.
clinical_trials:
- name: NCT03725202
  phase: PHASE_III
  status: COMPLETED
  description: >-
    SELECT-GCA randomized participants with giant cell arteritis to upadacitinib
    plus a 26-week glucocorticoid taper or placebo plus a 52-week taper. It is
    relevant to an important etiology of aortitis but did not establish an
    aortitis-specific structural or imaging benefit.
  notes: No aortitis target phenotype is assigned because aortic involvement was not a trial-specific endpoint.
  evidence:
  - reference: clinicaltrials:NCT03725202
    reference_title: "A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Giant Cell Arteritis: SELECT-GCA"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The objective of Period 1 is to evaluate the efficacy of upadacitinib in
      combination with a 26-week corticosteroid (CS) taper regimen compared to
      placebo in combination with a 52-week CS taper regimen, as measured by the
      proportion of participants in sustained remission at Week 52
    explanation: Documents the completed phase III trial design and primary remission objective.
- name: NCT06271018
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    TILT is a prospective French multicenter observational study of biosimilar
    tocilizumab plus short-course glucocorticoids in GCA with active aortitis,
    designed to evaluate vessel inflammation and damage by modern imaging. Its
    results were not yet available at the review cutoff.
  target_phenotypes:
  - preferred_term: Aortitis
    term:
      id: HP:6001461
      label: Aortitis
  evidence:
  - reference: clinicaltrials:NCT06271018
    reference_title: Prospective, Observational Study Assessing Safety and Efficacy of Biosimilar of Tocilizumab in Giant Cell Arteritis (GCA) With Active Aortitis
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is a french multicenter observational study assessing safety and
      efficacy of biosimilar of Tocilizumab in Giant Cell Arteritis (GCA) with
      active aortitis, including 14 reference centers
    explanation: Establishes the aortitis-specific observational study scope; no outcome claim is made.
animal_models:
- species: Mouse (Mus musculus)
  background: SCID mouse bearing a human temporal-artery xenograft
  description: >-
    Human temporal arteries with giant-cell arteritis remain inflamed after
    engraftment into SCID mice, enabling in-vivo study of vascular immune
    persistence and glucocorticoid response. The model uses temporal artery,
    not aorta, and does not reproduce systemic disease or chronic aortic
    remodeling and aneurysm formation.
  associated_phenotypes:
  - Persistent human arterial inflammation
  - Cytokine expression after glucocorticoid treatment
  evidence:
  - reference: PMID:9185506
    reference_title: Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      GCA is self-sustained in temporal arteries engrafted into SCID mice,
      providing a model in which the mechanisms of action and limitations of
      glucocorticoid therapy can be examined in vivo.
    explanation: Supports model validity for persistent human arterial inflammation while the description states its aortic limitations.
discussions:
- discussion_id: disc_aortitis_cia_immunosuppression
  prompt: Does postoperative immunosuppression improve aortic outcomes in clinically isolated aortitis?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - has_subtypes#Clinically isolated aortitis
  - treatments#Specialist multidisciplinary follow-up and aortic surveillance
  rationale: >-
    Clinically isolated aortitis is often discovered only after resection and
    carries subsequent vascular risk, but surveillance is better supported than
    a uniform immunosuppressive regimen. Etiology, residual active inflammation,
    and surgical selection complicate treatment comparisons; no disease-level
    efficacy claim was added.
  evidence:
  - reference: PMID:40099651
    reference_title: "Isolated aortitis - is it truly isolated? An approach to diagnosis and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Surveillance of patients with IA with repeated clinical assessments and imaging
      is recommended.
    explanation: Supports surveillance while leaving postoperative immunosuppression unresolved.
  posed_date: "2026-08-05T00:00:00Z"
- discussion_id: disc_aortitis_model_fidelity
  prompt: Which experimental model can reproduce chronic human aortic inflammation, remodeling, and aneurysm formation?
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - animal_models#Mouse (Mus musculus)
  rationale: >-
    The human temporal-artery SCID chimera preserves an arterial immune lesion
    and enables perturbation studies, but its anatomy and time course do not
    model chronic aortic remodeling. Aortic-tissue and longitudinal models are
    needed before extrapolating model interventions to aortic outcomes.
  evidence:
  - reference: PMID:9185506
    reference_title: Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      GCA is self-sustained in temporal arteries engrafted into SCID mice,
      providing a model in which the mechanisms of action and limitations of
      glucocorticoid therapy can be examined in vivo.
    explanation: Defines what the model supports and, by its temporal-artery anatomy, the principal mismatch.
  posed_date: "2026-08-05T00:00:00Z"
references: []
datasets:
- accession: geo:GSE306150
  title: Spatial gene expression profiling of aortitis samples.
  data_type: SPATIAL_TRANSCRIPTOMICS
  description: 10X Xenium profiling of ascending aorta samples isolated from subjects with aortitis.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 10
  publication: PMID:41948935
  notes: Identified by GEO DataSets index search for Aortitis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

Deep Research

2
Falcon ▸
1. Disease Information
Edison Scientific Literature 45 citations 2026-05-05T23:44:14.822781

1. Disease Information

1.1 Overview / definition

Aortitis is explicitly defined as “inflammation of the aorta”. (staniforth2024aortitisincreasesthe pages 1-2)

Clinically, it is best conceptualized as a syndrome with divergent causes and management imperatives (e.g., immunosuppression for inflammatory aortitis vs antimicrobials ± surgery for infectious aortitis). (arcilla2025thegreatvasculitis pages 7-9, staniforth2024aortitisincreasesthe pages 1-2)

1.2 Key identifiers (requested: OMIM/Orphanet/ICD/MeSH/MONDO)

  • Not found in retrieved texts: ICD-10/ICD-11 codes, MeSH headings/unique IDs, MONDO IDs, Orphanet IDs. (staniforth2024aortitisincreasesthe pages 9-11, staniforth2024aortitisincreasesthe pages 2-4)
  • Common literature labels/synonyms used in retrieved texts (non-exhaustive):
  • Aortitis; infectious aortitis; noninfectious aortitis; inflammatory aortitis; clinically isolated aortitis (CIA); “idiopathic aortitis”; “giant cell aortitis”. (staniforth2024aortitisincreasesthe pages 1-2, staniforth2024aortitisincreasesthe pages 9-11, staniforth2024aortitisincreasesthe pages 2-4)

1.3 Evidence sources

The information here is derived from aggregated disease-level resources (systematic reviews, narrative reviews, cohort studies) and case-based reviews; several sources are surgical-cohort based (histology from aortic resections) and thus reflect a selected population (patients undergoing major aortic surgery). (staniforth2024aortitisincreasesthe pages 1-2, bosch2023imagingindiagnosis pages 1-2, arcilla2025thegreatvasculitis pages 7-9)

2. Etiology

2.1 Major causal categories

  1. Noninfectious (immune-mediated) aortitis
  2. Large-vessel vasculitis: Giant cell arteritis (GCA), Takayasu arteritis (TAK), and variable-vessel vasculitis such as Behçet disease can involve the aorta/major branches. (popescu2024imaginginlarge pages 4-5)
  3. Clinically isolated aortitis (CIA): defined as aortitis without systemic vasculitis or other inflammatory conditions, often detected on histology after aortic surgery. (staniforth2024aortitisincreasesthe pages 1-2)

  4. IgG4-related periaortitis/aortitis is a distinct fibro-inflammatory entity (review evidence retrieved is 2025). (wang2025unravelingthecomplexity pages 6-7)

  5. Infectious aortitis

  6. Pathogens include Salmonella, Staphylococcus aureus, Streptococcus spp., Enterococcus, Haemophilus influenzae, Mycobacterium tuberculosis, Treponema pallidum, fungi, and others; infection can seed damaged aortic wall (e.g., atherosclerosis) with pseudoaneurysm formation and high rupture risk. (arcilla2025thegreatvasculitis pages 7-9, arcilla2025thegreatvasculitis pages 6-7)

  7. Drug-induced aortitis

  8. G-CSF–induced aortitis has been characterized through systematic case aggregation, particularly in chemotherapy settings. (zhao2024literaturereviewanalysis pages 1-2, zhao2024literaturereviewanalysis pages 5-7)

2.2 Risk factors

  • CIA/noninfectious surgical aortitis (surgical cohort): increased age, female sex, current smoking, and prior inflammatory disease were associated with histologic aortitis; bicuspid aortic valve was associated with reduced odds in that cohort. (staniforth2024aortitisincreasesthe pages 6-8)
  • Infectious aortitis: risk factors include trauma, atherosclerotic plaques, congenital malformations, immunosuppression, infections, and malignancy. (arcilla2025thegreatvasculitis pages 1-3)
  • G-CSF–induced: predominantly older women; common setting is breast cancer chemotherapy; geographic clustering in East Asia reported in the case-review dataset. (zhao2024literaturereviewanalysis pages 1-2, zhao2024literaturereviewanalysis pages 2-3)

2.3 Protective factors

A bicuspid aortic valve was associated with lower likelihood of histologic aortitis in a surgical cohort (association, not necessarily causal protection). (staniforth2024aortitisincreasesthe pages 6-8)

2.4 Gene–environment interactions

Direct gene–environment interaction studies specific to “aortitis” were not retrieved. However, TAK genetic susceptibility (e.g., MLX variant; HLA associations) plausibly interacts with inflammatory triggers; infectious mimics can also induce autoantibodies and confound immune phenotyping. (tamura2018singlenucleotidepolymorphismof pages 6-7, arcilla2025thegreatvasculitis pages 7-9)

3. Phenotypes (with HPO suggestions)

Aortitis phenotypes vary by etiology and vascular territory involved. A curated phenotype-to-HPO mapping table is provided below.

Phenotype (plain) HPO term(s) suggestion Evidence details (including onset/course, frequencies, quantitative lab values) Major etiologies/subtypes where seen Key citations (pqac ids)
Constitutional symptoms / malaise / fatigue / weight loss HP:0012378 Fatigue; HP:0004305 Malaise; HP:0001824 Weight loss Aortitis often presents nonspecifically with fatigue, feeling generally ill, and weight loss; GCA usually has gradual onset over weeks to months; TAK has a prodromal constitutional phase; IgG4-related PAO/PA also includes fatigue/weight loss/malaise; Behçet often relapsing-remitting General aortitis, GCA, TAK, IgG4-related aortitis, Behçet disease (staniforth2024aortitisincreasesthe pages 1-2, popescu2024imaginginlarge pages 4-5, wang2025unravelingthecomplexity pages 6-7)
Fever HP:0001945 Fever Fever is common in GCA and TAK constitutional phases; in G-CSF-induced aortitis, 68/72 (96%) were symptomatic, commonly with fever; mean temperatures around 38.6°C; infectious aortitis also commonly presents with systemic inflammatory illness GCA, TAK, G-CSF-induced aortitis, infectious aortitis (popescu2024imaginginlarge pages 4-5, zhao2024literaturereviewanalysis pages 5-7, arcilla2025thegreatvasculitis pages 7-9)
Pain (chest, back, abdominal, neck, sore throat) HP:0100749 Chest pain; HP:0002027 Abdominal pain; HP:0003418 Back pain; HP:0003202 Cervical pain G-CSF-induced aortitis commonly caused fever plus pain (chest, back, abdominal, neck, sore throat); IgG4-related PAO/PA commonly causes abdominal or back pain; thoracic involvement may cause chest pain and dyspnea G-CSF-induced aortitis, IgG4-related aortitis/periaortitis (zhao2024literaturereviewanalysis pages 5-7, wang2025unravelingthecomplexity pages 6-7)
Polymyalgia-type proximal stiffness HP:0002829 Arthralgia; HP:0003326 Myalgia Noninfectious aortitis may include polymyalgic symptoms with proximal shoulder/pelvic girdle stiffness; polymyalgia rheumatica co-occurs in 40–60% of GCA Noninfectious aortitis, especially GCA-associated aortitis (staniforth2024aortitisincreasesthe pages 1-2, popescu2024imaginginlarge pages 4-5)
Headache HP:0002315 Headache GCA cranial phenotype includes headache; onset usually gradual over weeks to months, though ~20% may be abrupt GCA-associated aortitis/large-vessel GCA (popescu2024imaginginlarge pages 4-5)
Jaw or tongue claudication HP:0200044 Jaw claudication Characteristic cranial ischemic symptom in GCA; occurs with chewing and supports cranial involvement in patients who may also have aortitis/large-vessel disease GCA-associated aortitis (popescu2024imaginginlarge pages 4-5)
Visual loss / ischemic optic neuropathy HP:0000572 Visual loss; HP:0000648 Optic atrophy (suggestive downstream term if chronic) In GCA, vascular occlusion can cause cranial ischemia and ischemic optic neuropathy; vision loss is typically painless and irreversible; ischemic optic neuropathy reported in ~14% in imaging review context GCA-associated aortitis/large-vessel GCA (popescu2024imaginginlarge pages 4-5)
Limb claudication / arm or leg claudication HP:0004936 Intermittent claudication Aortic or main-branch involvement in GCA can cause limb claudication; TAK vascular phase includes arm or leg claudication; IgG4 iliac/femoral disease can also cause claudication GCA, TAK, IgG4-related aortitis (popescu2024imaginginlarge pages 4-5, chan2025strokeaorticregurgitation pages 2-4, wang2025unravelingthecomplexity pages 6-7)
Pulseless vascular phase / pulse deficits HP:0031808 Abnormality of peripheral pulse TAK classically progresses from a constitutional “pre-pulseless” phase to a “pulseless” vascular phase with stenotic lesions in >90% TAK-associated aortitis (popescu2024imaginginlarge pages 4-5)
Hypertension HP:0000822 Hypertension Common in TAK (30–90%); IgG4-related renal artery involvement can also cause hypertension TAK, IgG4-related aortitis (popescu2024imaginginlarge pages 4-5, wang2025unravelingthecomplexity pages 6-7)
Stroke / transient ischemic attack HP:0001297 Stroke; HP:0002326 Transient ischemic attack TIAs/strokes occur in 2–7% of GCA and 10–20% of TAK; aortitis cohorts also report increased stroke risk during follow-up GCA, TAK, general aortitis complications (popescu2024imaginginlarge pages 4-5, staniforth2024aortitisincreasesthe pages 8-9)
Mucocutaneous ulcers HP:0000197 Oral ulcer; HP:0000135 Genital ulcer Behçet disease phenotype includes oral and genital ulcers with frequent relapses/remissions and potential large-vessel aortitis/aneurysm/thrombosis Behçet disease-associated aortitis (popescu2024imaginginlarge pages 4-5)
Uveitis / ocular inflammation HP:0000554 Uveitis Behçet disease includes uveitis as a key systemic phenotype accompanying possible large-vessel complications Behçet disease-associated aortitis (popescu2024imaginginlarge pages 4-5)
Thrombosis / occlusion HP:0004930 Venous thrombosis; HP:0012393 Arterial thrombosis; HP:0004417 Vascular occlusion Behçet large-vessel involvement may include thrombosis and occlusion; aortitis overall can cause stenosis/occlusion; infectious aortitis can present with pseudoaneurysm and occlusive thrombus Behçet disease, infectious aortitis, general aortitis (popescu2024imaginginlarge pages 4-5, staniforth2024aortitisincreasesthe pages 1-2, arcilla2025thegreatvasculitis pages 7-9)
Elevated CRP / ESR / inflammatory markers HP:0011227 Elevated C-reactive protein level; HP:0003565 Increased erythrocyte sedimentation rate Aortitis workup commonly shows high inflammatory markers; G-CSF-induced cases had CRP means ~26.06 ± 15.39 mg/dL (filgrastim), 24.81 ± 9.65 mg/dL (pegfilgrastim), 10.45 ± 9.91 mg/dL (lenograstim); giant cell aortitis case had CRP 82 mg/L and ESR 140 mm/h General aortitis, G-CSF-induced aortitis, giant cell aortitis case, IgG4-related aortitis (staniforth2024aortitisincreasesthe pages 1-2, zhao2024literaturereviewanalysis pages 5-7, chan2025strokeaorticregurgitation pages 2-4, wang2025unravelingthecomplexity pages 6-7)
Leukocytosis HP:0001974 Leukocytosis Reported as a common laboratory abnormality in infectious/inflammatory aortitis differential workup Infectious aortitis and mimics (arcilla2025thegreatvasculitis pages 7-9)
Thrombocytosis HP:0001873 Thrombocytosis Mild-to-moderate thrombocytosis reported in infectious/inflammatory aortitis differential workup Infectious aortitis and mimics (arcilla2025thegreatvasculitis pages 7-9)
Normocytic/normochromic anemia HP:0001877 Abnormality of erythrocytes; HP:0001892 Normocytic anemia Normochromic/normocytic anemia described among laboratory abnormalities in infectious/inflammatory aortitis evaluation Infectious aortitis and mimics (arcilla2025thegreatvasculitis pages 7-9)
Hypoalbuminemia HP:0003073 Hypoalbuminemia Reported among laboratory abnormalities in infectious/inflammatory aortitis differential workup Infectious aortitis and mimics (arcilla2025thegreatvasculitis pages 7-9)
Polyclonal hypergammaglobulinemia HP:0003237 Hypergammaglobulinemia Reported in inflammatory/infectious aortitis differential workup Infectious/inflammatory aortitis (arcilla2025thegreatvasculitis pages 7-9)
Aortic aneurysm HP:0002617 Aortic aneurysm A major downstream complication across aortitis subtypes. In surgical cohort, re-operations for new aneurysm formation were increased (14% with aortitis vs 3.8% without); GCA CT study reported >20% (12/54) developing aneurysm after 4–10 years; Behçet and infectious aortitis also associated with aneurysms General aortitis, GCA, Behçet, infectious aortitis, IgG4-related aortitis (staniforth2024aortitisincreasesthe pages 4-6, popescu2024imaginginlarge pages 7-9, popescu2024imaginginlarge pages 4-5, arcilla2025thegreatvasculitis pages 7-9, wang2025unravelingthecomplexity pages 6-7)
Aortic dissection HP:0002647 Aortic dissection Aortitis may present as dissection; G-CSF-induced review documented dissections among complications; giant cell aortitis case involved aneurysmal/root pathology; infectious/IgG4-related disease can also progress to dissection General aortitis, G-CSF-induced, giant cell aortitis, IgG4-related aortitis (staniforth2024aortitisincreasesthe pages 1-2, zhao2024literaturereviewanalysis pages 5-7, chan2025strokeaorticregurgitation pages 2-4, wang2025unravelingthecomplexity pages 6-7)
Stenosis / arterial narrowing / occlusion HP:0005290 Arterial stenosis; HP:0004417 Vascular occlusion Aortitis can cause wall thickening, loss of elasticity, stenosis, and occlusion; TAK has stenotic lesions in >90%; CTA shows luminal stenosis/narrowing General aortitis, TAK, infectious aortitis (staniforth2024aortitisincreasesthe pages 1-2, popescu2024imaginginlarge pages 4-5, popescu2024imaginginlarge pages 5-7)
Aortic regurgitation HP:0001659 Aortic valve regurgitation Case report of giant cell aortitis described severe aortic regurgitation with aortic root aneurysm and destructive transmural inflammation; MLX variant study in TAK linked severity with aortic regurgitation morbidity Giant cell aortitis case, Takayasu arteritis (chan2025strokeaorticregurgitation pages 2-4)
Dyspnea / compressive thoracic symptoms HP:0002094 Dyspnea Thoracic IgG4-related lesions may cause chest pain, dyspnea, and mediastinal compression; may reflect advanced local disease IgG4-related aortitis/periaortitis (wang2025unravelingthecomplexity pages 6-7)
Abdominal angina / bowel ischemia HP:0031106 Intestinal ischemia; HP:0002574 Abdominal pain Mesenteric involvement in IgG4-related disease may cause abdominal angina or bowel ischemia IgG4-related aortitis/periaortitis (wang2025unravelingthecomplexity pages 6-7)
Renal ischemia / hydronephrosis / renal injury HP:0000105 Renal insufficiency; HP:0000126 Hydronephrosis IgG4-related renal artery/periaortic involvement can cause ischemic nephropathy, post-obstructive hydronephrosis, and potentially permanent renal injury IgG4-related aortitis/periaortitis (wang2025unravelingthecomplexity pages 6-7)

Table: This table summarizes key clinical, laboratory, and complication phenotypes reported for aortitis across major etiologic subtypes, with suggested HPO mappings. It is useful for disease knowledge-base curation because it links observed features to onset/course details, frequencies where available, and source-backed evidence.

Key phenotype highlights with quantitative data (when available): - GCA: gradual onset over weeks–months (≈20% abrupt), cranial/constitutional symptoms; polymyalgia rheumatica in 40–60%; TIAs/strokes 2–7%; aortic/major branch involvement 27%. (popescu2024imaginginlarge pages 4-5) - TAK: constitutional phase → pulseless vascular phase; stenotic lesions >90%; aneurysms ≈25%; hypertension 30–90%; stroke/TIA 10–20%. (popescu2024imaginginlarge pages 4-5) - Behçet: large vascular involvement up to 40%; mortality ≈4%; frequent relapsing course. (popescu2024imaginginlarge pages 4-5) - G-CSF–induced aortitis: symptomatic in 96% (68/72); fever and pain common; CRP markedly elevated; blood cultures uniformly negative in the compiled case series. (zhao2024literaturereviewanalysis pages 5-7)

Quality-of-life measures (EQ-5D/SF-36/PROMIS) were not reported in the retrieved texts; QoL impact is inferred from chronicity/relapse and major vascular complications rather than quantified. (popescu2024imaginginlarge pages 4-5, staniforth2024aortitisincreasesthe pages 8-9)

4. Genetic / Molecular Information

4.1 Genetic susceptibility (human)

  • GCA: HLA association reported with HLA-DRB*04; non-HLA polymorphisms noted in a narrative imaging review include PTPN22, NOS2, ERAP1, REL, PRKQC. (popescu2024imaginginlarge pages 4-5)
  • TAK: persistent genetic risk at HLA-B*52:01 and susceptibility loci (HLA-B/MICA; HLA-DQB1/HLA-DRB1) were reported in review; a mechanistic genetics study links MLX rs665268 (Q139R) to TAK severity and aortic regurgitation. (popescu2024imaginginlarge pages 4-5, tamura2018singlenucleotidepolymorphismof pages 2-3)
  • Behçet disease: susceptibility at MHC class I, notably HLA-B51. (popescu2024imaginginlarge pages 4-5)

4.2 Mechanistic pathways and causal chains

  • TAK MLX-Q139R → inflammasome axis (primary research): MLX-Q139R increases MondoA–MLX activity, upregulates TXNIP, and promotes NLRP3 inflammasome activation with increased IL-1β, oxidative stress, and impaired autophagy (mTOR axis), supporting a causal chain from genotype to macrophage-driven vascular inflammation. (tamura2018singlenucleotidepolymorphismof pages 6-7, tamura2018singlenucleotidepolymorphismof pages 2-3)
  • GCA vascular immunopathology (review evidence retrieved is 2026): initiation includes activation of arterial-wall dendritic cells, T cell invasion enabled by monocyte-derived MMP-9, NETs, macrophage polarization, and tertiary lymphoid organ signals (CXCL13/BAFF/APRIL/LT-β), implicating innate and adaptive immune circuits and stromal remodeling. (muratore2026treatmentstrategiesin pages 29-33)

4.3 Suggested GO biological processes and CL cell types

(These are suggested ontology mappings based on mechanisms described in retrieved sources.) - GO terms (suggested): inflammatory response; granulomatous inflammatory response; leukocyte migration; cytokine-mediated signaling pathway; inflammasome complex assembly; autophagy; extracellular matrix organization; angiogenesis/neovascularization. (popescu2024imaginginlarge pages 4-5, tamura2018singlenucleotidepolymorphismof pages 6-7, muratore2026treatmentstrategiesin pages 29-33) - CL terms (suggested): macrophage / monocyte-derived macrophage; CD4-positive T cell; CD8-positive T cell; dendritic cell (arterial wall); neutrophil; B cell; vascular endothelial cell; vascular smooth muscle cell; fibroblast. (tamura2018singlenucleotidepolymorphismof pages 6-7, muratore2026treatmentstrategiesin pages 29-33)

5. Environmental Information

5.1 Infectious agents

Infectious aortitis pathogens frequently cited include Salmonella, Staphylococcus aureus, Streptococcus spp., Enterococcus, Haemophilus influenzae, Mycobacterium tuberculosis, Treponema pallidum, fungi, and others. (arcilla2025thegreatvasculitis pages 7-9, arcilla2025thegreatvasculitis pages 6-7)

5.2 Drug exposure

G-CSF exposure (notably pegfilgrastim) is associated with rare aortitis, most commonly presenting within days after dosing in the compiled case series (agent-dependent mean onset times). (zhao2024literaturereviewanalysis pages 5-7)

Lifestyle/environmental risks (e.g., smoking) were associated with surgical-cohort aortitis risk. (staniforth2024aortitisincreasesthe pages 6-8)

6. Mechanism / Pathophysiology

6.1 Upstream-to-downstream causal chain (integrated)

Aortitis pathophysiology can be summarized as: 1. Trigger/etiology (autoimmune LVV, infection, drug-induced immune activation) → 2. Aortic wall inflammation (granulomatous inflammation in GCA/TAK; neutrophil-predominant infiltration in infection; IgG4+ lymphoplasmacytic infiltration with storiform fibrosis in IgG4-RD) → 3. Structural remodeling (intimal hyperplasia, neovascularization, fibrosis; medial degradation) → 4. Clinical consequences: aneurysm, dissection, stenosis/occlusion, ischemia, stroke, valve involvement (aortic regurgitation), rupture. (popescu2024imaginginlarge pages 4-5, arcilla2025thegreatvasculitis pages 7-9, wang2025unravelingthecomplexity pages 6-7, staniforth2024aortitisincreasesthe pages 1-2)

6.2 Tissue damage mechanisms

  • Stenosis/occlusion and aneurysm/dissection arise from wall thickening, loss of elasticity, and inflammatory destruction/remodeling. (staniforth2024aortitisincreasesthe pages 1-2, popescu2024imaginginlarge pages 4-5)
  • Infectious aortitis often produces pseudoaneurysm and saccular morphology, with rupture risk heightened by wall necrosis and gas/edema/fat stranding in periaortic tissues. (arcilla2025thegreatvasculitis pages 7-9)

7. Anatomical Structures Affected

7.1 Organ/system level

  • Primary: aorta and major branches (cardiovascular system). (staniforth2024aortitisincreasesthe pages 1-2, popescu2024imaginginlarge pages 4-5)
  • Secondary/complications: heart valves (aortic regurgitation), brain (stroke), kidneys (renal ischemia/hydronephrosis in IgG4-related disease), bowel (mesenteric ischemia). (chan2025strokeaorticregurgitation pages 2-4, popescu2024imaginginlarge pages 4-5, wang2025unravelingthecomplexity pages 6-7)

7.2 Suggested UBERON terms (not exhaustive; suggestions)

  • UBERON:0000947 (aorta), plus segment-level (thoracic aorta, abdominal aorta), and branch arteries (subclavian, axillary, carotid) depending on phenotype. Imaging reviews emphasize aorta and its branches. (popescu2024imaginginlarge pages 1-2, popescu2024imaginginlarge pages 7-9)

8. Temporal Development

  • GCA: typically subacute onset over weeks–months; may be abrupt (~20%). (popescu2024imaginginlarge pages 4-5)
  • TAK: constitutional “pre-pulseless” phase progressing to “pulseless” vascular phase with chronic stenosis/aneurysm complications. (popescu2024imaginginlarge pages 4-5)
  • CIA: frequently asymptomatic until incidentally found on surgical pathology; requires prolonged surveillance due to late complications. (staniforth2024aortitisincreasesthe pages 1-2, staniforth2024aortitisincreasesthe pages 8-9)
  • G-CSF-induced: onset typically within days after exposure (agent-specific mean onset times in case review). (zhao2024literaturereviewanalysis pages 5-7)

9. Inheritance and Population

9.1 Epidemiology (selected quantitative data from retrieved sources)

  • Histology-confirmed aortitis in major aortic surgery: prevalence 10.6% (57/537) with 75% CIA, in a single-center cohort with high sampling rate (88%). (staniforth2024aortitisincreasesthe pages 1-2)
  • GCA: incidence about 44 per 100,000 persons >50 (Northern Europe) and prevalence estimates in another PET-focused review as 9–25 per 100,000 (>50). (popescu2024imaginginlarge pages 1-2, nassarmadji202318fluorodeoxyglucosepositronemission pages 1-2)
  • TAK: annual incidence 0.4–3.4 per 1,000,000. (popescu2024imaginginlarge pages 1-2)

9.2 Population/sex patterns

  • CIA/surgical cohort aortitis associated with female sex. (staniforth2024aortitisincreasesthe pages 6-8)
  • G-CSF-induced aortitis: ~81% female with mean age ~62 years in compiled case series. (zhao2024literaturereviewanalysis pages 1-2)

10. Diagnostics

10.1 Laboratory evaluation (common elements)

  • In aortitis evaluation, inflammatory markers (ESR/CRP) are commonly used, but may be insensitive/nonspecific for vascular inflammation; infectious workup includes cultures and broad serologies. (ahlman2023advancedmolecularimaging pages 1-2, arcilla2025thegreatvasculitis pages 7-9)
  • Infectious/inflammatory mimics: leucocytosis, thrombocytosis, normocytic anemia, hypoalbuminemia, polyclonal hypergammaglobulinemia. (arcilla2025thegreatvasculitis pages 7-9)

10.2 Imaging: current standards and performance

EULAR 2023 evidence base (systematic review/meta-analysis) for GCA imaging: - Ultrasound, MRI, and FDG-PET have “good performance” for GCA diagnosis; in low risk-of-bias studies, ultrasound sensitivity/specificity 88% / 96% and pooled LR+ 20.07, LR− 0.13. (bosch2023imagingindiagnosis pages 3-4) - Ultrasound assessing both cranial and extracranial arteries improves sensitivity (93% vs 80%) with similar specificity. (bosch2023imagingindiagnosis pages 1-2) - FDG-PET pooled sensitivity/specificity reported as 76% / 95% (context: GCA imaging studies in the SLR). (bosch2023imagingindiagnosis pages 1-2)

Practical CTA/MRI/PET criteria from narrative imaging review (2024): - Active inflammation suggested by wall thickening >2 mm (aorta) and >1 mm (branch vessels) on CTA/MRI. (popescu2024imaginginlarge pages 7-9) - Arterial wall enhancement defined as >20 HU increase compared to unenhanced CT. (popescu2024imaginginlarge pages 7-9) - PET positivity criterion: segmental FDG uptake ≥ liver. (popescu2024imaginginlarge pages 7-9)

FDG-PET/CT in clinical practice (2023 review): - For cranial artery involvement (when performed before/≤72h after glucocorticoids), sensitivity 82–92% and specificity 85–100% reported. (nassarmadji202318fluorodeoxyglucosepositronemission pages 1-2)

10.3 Histopathology

  • Surgical series highlight the importance of intra-operative sampling: aortitis diagnosis often relies on histology, and CIA may be missed without routine sampling. (staniforth2024aortitisincreasesthe pages 1-2)
  • Infectious aortitis may show neutrophilic infiltration but biopsy may be risky in fragile walls. (arcilla2025thegreatvasculitis pages 7-9)

10.4 Differential diagnosis

A key diagnostic principle is to exclude infection and malignancy before immunosuppression; infectious aortitis can induce autoantibodies (ANCA/MPO/PR3), mimicking primary vasculitis. (arcilla2025thegreatvasculitis pages 6-7, arcilla2025thegreatvasculitis pages 7-9)

11. Outcome / Prognosis

  • Surgical cohort outcomes: aortitis increased re-operation risk; re-operation rate was roughly doubled (17.5% vs 9.4%). (staniforth2024aortitisincreasesthe pages 1-2)
  • Long-term complications: vascular stenosis, stroke risk, and new aneurysm formation are emphasized, with cited studies reporting 58% 5-year vascular complication rates in a French series and new aneurysm development in CIA cohorts (as cited in the surgical paper). (staniforth2024aortitisincreasesthe pages 8-9)
  • Infectious aortitis: high mortality noted for thoracic infectious aortitis (reported up to 30–50% in a case-based review). (arcilla2025thegreatvasculitis pages 1-3)

12. Treatment

12.1 Noninfectious/CIA and LVV-associated aortitis

  • Center practice regimen (CIA/noninfectious): prednisolone 0.75–1 mg/kg plus methotrexate 20–25 mg/week; refractory cases may use pulsed IV cyclophosphamide 15 mg/kg; tocilizumab 162 mg SC weekly used for relapsing/refractory disease after failure of two conventional strategies. (staniforth2024aortitisincreasesthe pages 8-9)

  • Tocilizumab real-world effectiveness (extracranial GCA/LV-GCA and TAK; 2025 observational): at 12 months, remission 74.5% (LV-GCA) and 76.9% (TAK); imaging-complete resolution only 18.9% and 21.1%, respectively; severe infections led to discontinuation in 4 LV-GCA and 3 TAK patients. (lasateja2025tocilizumabinextracranial pages 1-2)

  • GC + TCZ RCT benchmark (GiACTA; summarized in 2024 trial protocol): sustained remission at 52 weeks 56%/53% (weekly/q2w TCZ) vs 14%/18% (GC alone). (kreis2024themeteoriticstrial pages 1-2)

12.2 Infectious aortitis

  • Early empiric broad-spectrum antibiotics covering Gram-positive cocci and Gram-negative rods; ampicillin/cephalosporins suggested empirically for Salmonella; prolonged therapy often required (≥6–8 weeks), especially with endovascular repair; surgery/endovascular (TEVAR/EVAR) indicated for rapid expansion/large aneurysm but with infection-related complication risk. (arcilla2025thegreatvasculitis pages 7-9)

12.3 MAXO term suggestions (examples)

  • Glucocorticoid therapy; methotrexate therapy; cyclophosphamide therapy; IL-6 receptor antagonist therapy (tocilizumab); antimicrobial therapy; endovascular aortic repair; open surgical aortic repair; imaging surveillance. (staniforth2024aortitisincreasesthe pages 8-9, arcilla2025thegreatvasculitis pages 7-9, lasateja2025tocilizumabinextracranial pages 1-2)

13. Prevention

Evidence retrieved is limited. Practical prevention/mitigation approaches include: - Secondary prevention of complications via long-term surveillance imaging (annual CT aortogram ≥5 years in one center protocol) and cardiovascular risk modification measures (statins, beta-blockers, ACE inhibitors, antithrombotics) used in clinical practice. (staniforth2024aortitisincreasesthe pages 8-9) - For biologic therapy: TB screening (PPD/QuantiFERON, chest X-ray) and isoniazid prophylaxis for latent infection before biologics in one multicenter observational practice description. (lasateja2025tocilizumabinextracranial pages 2-4)

14. Other Species / Natural Disease

No retrieved evidence in this run addressed naturally occurring aortitis across non-human species or zoonotic considerations.

15. Model Organisms

No direct “aortitis model organism” papers were retrieved in this run. Mechanistic TAK genetics work used immune cell systems and vascular cells (e.g., PBMC-derived macrophages; human aortic smooth muscle cells) supporting in vitro mechanistic modeling. (tamura2018singlenucleotidepolymorphismof pages 6-7)

Recent developments (priority 2023–2024)

  1. Imaging evidence synthesis informing EULAR 2023 update: pooled diagnostic performance metrics for ultrasound/MRI/FDG-PET in GCA and evidence supporting inclusion of extracranial (axillary) ultrasound to increase sensitivity. (Aug 2023; https://doi.org/10.1136/rmdopen-2023-003379) (bosch2023imagingindiagnosis pages 1-2, bosch2023imagingindiagnosis pages 3-4)
  2. High-sampling surgical cohort redefining CIA prevalence and postoperative risk: histology-sampled prevalence 10.6% with 75% CIA; higher re-operation risk and identified risk associations (age, female sex, smoking, inflammatory disease). (Dec 2024; https://doi.org/10.3390/jcdd11120405) (staniforth2024aortitisincreasesthe pages 1-2, staniforth2024aortitisincreasesthe pages 6-8, staniforth2024aortitisincreasesthe media bd38afdc)
  3. Drug-induced aortitis (G-CSF) systematic case synthesis: 72-case dataset describing demographics, lesion distribution, complication rate (~4.2%), and recurrence on rechallenge, emphasizing diagnostic vigilance. (Dec 2024; https://doi.org/10.3389/fphar.2024.1487501) (zhao2024literaturereviewanalysis pages 1-2, zhao2024literaturereviewanalysis pages 5-7)

Key quantitative summary table (etiology/risk statistics)

Category Typical patient profile Key statistics Diagnostic clues (labs/imaging) Notes/quotes Key citations
Noninfectious: overall surgically identified aortitis / clinically isolated aortitis (CIA) Often older adults; more common in women; associated with smoking and prior inflammatory disease; many cases asymptomatic until aneurysm/dissection surgery In a major aortic surgery cohort, histology-confirmed aortitis prevalence was 10.6% (57/537); 75% of aortitis cases were CIA; CIA prevalence 8.0% (43/537); re-operation 17.5% vs 9.4% in non-aortitis; multivariable associations: age OR 1.03, female sex OR 4.10, current smoking OR 3.43, prior inflammatory disease OR 9.01; bicuspid aortic valve associated with lower odds OR 0.34 Elevated inflammatory markers; PET-CT to map inflammation; intra-operative histology is essential; annual CT aortogram suggested in follow-up “Aortitis, defined as inflammation of the aorta”; “75% were clinically isolated” (staniforth2024aortitisincreasesthe pages 1-2, staniforth2024aortitisincreasesthe pages 6-8, staniforth2024aortitisincreasesthe media bd38afdc)
Noninfectious: giant cell arteritis (GCA)-associated aortitis Usually adults >50 years; Northern European populations higher incidence; can coexist with PMR; risk factors for aneurysmal complications include male sex, smoking, hypertension, hyperlipidemia/coronary disease GCA incidence about 44/100,000 persons >50 in Northern Europe; aorta or major branch involvement in about 27% of GCA; in large-vessel GCA, aortic involvement 45–65%; thoracic aortic aneurysm/dissection incidence reported 8.2–33%; meta-analysis suggests ~3-fold increased TAA risk; one cohort found 3.1% TAA among 2,344 GCA patients; >20% (12/54) developed aortic aneurysm after 4–10 years in one CT study CTA/MRA/PET-CT/US; CTA/MRI wall-thickness thresholds suggesting active disease: >2 mm aorta, >1 mm branch vessels; PET uptake may identify higher-risk patients for future aneurysm “a granulomatous vasculitis”; “Imaging is essential”; “The literature review disclosed an increased incidence and relative risk of TAA among patients with GCA” (popescu2024imaginginlarge pages 4-5, strachan2025thoracicaorticaneurysm pages 2-4, popescu2024imaginginlarge pages 7-9, popescu2024imaginginlarge pages 1-2)
Noninfectious: Takayasu arteritis (TAK)-associated aortitis Typically younger individuals; often women; systemic large-vessel vasculitis affecting aorta and branches Annual incidence 0.4–3.4 per 1,000,000; TAK is “the primary cause of aortitis in younger individuals”; aorta/major branches involved in about 65%; coronary arteries 44%; pulmonary arteries 63%; stenotic lesions in >90%; aneurysms in about 25%; hypertension 30–90%; stroke/TIA 10–20% MRI first-line in suspected TAK; CTA shows circumferential wall thickening in active disease, later stenosis/occlusion; PET-CT can complement luminal imaging by showing active inflammation “characterized by variable degrees of inflammation... of all arterial layers (panarteritis)” (popescu2024imaginginlarge pages 4-5, popescu2024imaginginlarge pages 7-9, popescu2024imaginginlarge pages 1-2)
Noninfectious: Behçet disease-associated aortitis/large-vessel vasculitis Often younger to middle-aged adults; autoinflammatory/systemic vasculitis phenotype; HLA-B51 association noted in review Up to 40% may experience large vascular complications; mortality around 4% CTA/MRA/PET-CT/US depending territory; evaluate aneurysm, thrombosis, arterial wall inflammation “mainly considered an auto-inflammatory systemic vasculitis” (popescu2024imaginginlarge pages 4-5)
Noninfectious: drug-induced aortitis (G-CSF-associated) Predominantly older women receiving chemotherapy; especially breast cancer; also reported in healthy stem-cell donors; majority reported from Asian populations Review of 72 patients: 58 female/14 male (80.6% female), mean age 61.83 ± 10.30 years; pegfilgrastim implicated most often (63.4%); lesion distribution: aortic arch 36.11%, abdominal aorta 26.39%, thoracic aorta 22.22%; 4/72 asymptomatic; complications in 3/72 (~4.2%) including dissection/aneurysm; recurrence after rechallenge reported Typically fever/pain with elevated CRP and negative blood cultures; CT most often identifies aortic arch/branch involvement “Most patients had a good prognosis, but 3 cases developed complications”; “G-CSF-induced aortitis was also found in 4 asymptomatic patients” (zhao2024literaturereviewanalysis pages 1-2, zhao2024literaturereviewanalysis pages 5-7, zhao2024literaturereviewanalysis pages 7-8, zhao2024literaturereviewanalysis pages 2-3)
Infectious aortitis: overall bacterial/fungal/mycobacterial/spirochetal Often patients with atherosclerosis, damaged vessel wall, immunosuppression, infection, trauma, congenital abnormalities, or malignancy; may present with aneurysm, pseudoaneurysm, or sepsis-like syndrome Thoracic aortitis mortality reported 30–50%; blood cultures positive in only 50–82%; mycotic aneurysms account for 0.6–2% of all aortic aneurysms in Western populations; infectious aortitis more often abdominal (56% in cited series) Labs: leukocytosis, thrombocytosis, normocytic anemia, elevated inflammatory markers/CRP (often >100 mg/L in cited review); imaging: CTA/MRA/PET-CT/US; infected aneurysm clues include saccular morphology, peri-aortic edema/fat stranding, wall thickening, loss of contour, gas in wall “Differentiating between infectious and inflammatory cases is crucial”; “blood cultures (positive in only 50% to 82%) are recommended” (arcilla2025thegreatvasculitis pages 7-9, arcilla2025thegreatvasculitis pages 1-3, arcilla2025thegreatvasculitis pages 6-7)
Infectious aortitis: common pathogens / microbiology Bacterial predominance; consider bacteremia/endovascular seeding via vasa vasorum or damaged wall Gram-positive organisms about 44% in one review; Gram-negative rods 33%; intracellular/fastidious organisms 43%; Cox review notes Gram-positive bacteria account for about 60% of thoracic infections; common pathogens include Staphylococcus aureus, Streptococcus spp., Enterococcus, Salmonella, Haemophilus influenzae, Mycobacterium tuberculosis, Treponema pallidum, fungi Obtain repeated blood cultures, tissue culture/PCR/serologies; histology often shows neutrophilic infiltration; CTA/PET-CT used to define extent and plan intervention “Gram positive bacteria such as Staphylococcus, Enterococcus and Streptococcus accounting for approximately 60% of the infections” (arcilla2025thegreatvasculitis pages 7-9, arcilla2025thegreatvasculitis pages 6-7)
Infectious aortitis: management-relevant clues Patients may initially mimic primary vasculitis; wrong early immunosuppression can be harmful No large comparative trials; prolonged antibiotics typically at least 6–8 weeks with TEVAR/EVAR/open repair depending anatomy and infection control Broad-spectrum bactericidal therapy first; defer steroids/biologics until infection excluded; CTA gives high-resolution 3D anatomy, PET may help distinguish infection/inflammation and occult extent “Steroids and biological therapy were held until comprehensive investigations were completed”; “optimal approach must be decided on a case-by-case basis” (arcilla2025thegreatvasculitis pages 7-9, arcilla2025thegreatvasculitis pages 6-7)

Table: This table summarizes major noninfectious and infectious aortitis categories, highlighting patient profiles, quantitative epidemiology, diagnostic clues, and brief source-supported notes from the current evidence set. It is designed as a compact reference for comparing causes of aortitis and the numbers most relevant to diagnosis and risk stratification.

Real-world implementations / workflows

  • Surgical pathology workflow: routine intra-operative aortic sampling can uncover aortitis/CIA otherwise missed, changing follow-up intensity and rheumatology referral patterns. (staniforth2024aortitisincreasesthe pages 1-2)
  • Clinical imaging workflow: many centers increasingly integrate FDG-PET with CTA/MRA/US for LVV/aortitis assessment; reimbursement changes (CMS 2021) and guideline incorporation have accelerated PET use in some health systems. (ahlman2023advancedmolecularimaging pages 1-2)
  • Long-term monitoring: annual CT aortogram surveillance for at least 5 years after diagnosis is used in at least one specialized center pathway for CIA/noninfectious aortitis. (staniforth2024aortitisincreasesthe pages 8-9)

Items requested but not fully retrievable in this run

  • MONDO/Orphanet/ICD-10/ICD-11/MeSH identifiers: not present in retrieved full texts. (staniforth2024aortitisincreasesthe pages 9-11, staniforth2024aortitisincreasesthe pages 2-4)
  • PMIDs preferred: Several retrieved items are identified by DOI within text extracts but PMIDs were not consistently present in the extracted evidence snippets; therefore, DOI-based URLs are provided where available.
  • Model organism literature and cross-species natural disease: not retrieved.

References

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  15. (chan2025strokeaorticregurgitation pages 2-4): Elizabeth Chan. Stroke, aortic regurgitation and aortic aneurysm in younger female: case of giant cell aortitis and discussion. Academic Medicine & Surgery, Nov 2025. URL: https://doi.org/10.62186/001c.146456, doi:10.62186/001c.146456. This article has 0 citations.

  16. (staniforth2024aortitisincreasesthe pages 8-9): Edward Staniforth, Shirish Dubey, Iakovos Ttofi, Vanitha Perinparajah, Jasmina Ttofi, Rohit Vijjhalwar, Raman Uberoi, Ediri Sideso, and George Krasopoulos. Aortitis increases the risk of surgical complications and re-operations after major aortic surgery. Journal of Cardiovascular Development and Disease, 11:405, Dec 2024. URL: https://doi.org/10.3390/jcdd11120405, doi:10.3390/jcdd11120405. This article has 1 citations.

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  18. (popescu2024imaginginlarge pages 7-9): Ioana Popescu, Roxana Pintican, Luminita Cocarla, Benjamin Burger, Irina Sandu, George Popa, Alexandra Dadarlat, Raluca Rancea, Alexandru Oprea, Alexandru Goicea, Laura Damian, Alexandru Manea, Ruben Mateas, and Simona Manole. Imaging in large vessel vasculitis—a narrative review. Journal of Clinical Medicine, 13:6364, Oct 2024. URL: https://doi.org/10.3390/jcm13216364, doi:10.3390/jcm13216364. This article has 6 citations.

  19. (popescu2024imaginginlarge pages 5-7): Ioana Popescu, Roxana Pintican, Luminita Cocarla, Benjamin Burger, Irina Sandu, George Popa, Alexandra Dadarlat, Raluca Rancea, Alexandru Oprea, Alexandru Goicea, Laura Damian, Alexandru Manea, Ruben Mateas, and Simona Manole. Imaging in large vessel vasculitis—a narrative review. Journal of Clinical Medicine, 13:6364, Oct 2024. URL: https://doi.org/10.3390/jcm13216364, doi:10.3390/jcm13216364. This article has 6 citations.

  20. (tamura2018singlenucleotidepolymorphismof pages 2-3): Natsuko Tamura, Yasuhiro Maejima, Takayoshi Matsumura, Rick B. Vega, Eisuke Amiya, Yusuke Ito, Yuka Shiheido-Watanabe, Takashi Ashikaga, Issei Komuro, Daniel P. Kelly, Kenzo Hirao, and Mitsuaki Isobe. Single-nucleotide polymorphism of the mlx gene is associated with takayasu arteritis. Circulation: Genomic and Precision Medicine, 11:e002296, Oct 2018. URL: https://doi.org/10.1161/circgen.118.002296, doi:10.1161/circgen.118.002296. This article has 19 citations.

  21. (muratore2026treatmentstrategiesin pages 29-33): F Muratore, KJ Warrington, and C Dejaco. Treatment strategies in giant cell arteritis and polymyalgia rheumatica: beyond glucocorticoids. Unknown journal, 2026.

  22. (popescu2024imaginginlarge pages 1-2): Ioana Popescu, Roxana Pintican, Luminita Cocarla, Benjamin Burger, Irina Sandu, George Popa, Alexandra Dadarlat, Raluca Rancea, Alexandru Oprea, Alexandru Goicea, Laura Damian, Alexandru Manea, Ruben Mateas, and Simona Manole. Imaging in large vessel vasculitis—a narrative review. Journal of Clinical Medicine, 13:6364, Oct 2024. URL: https://doi.org/10.3390/jcm13216364, doi:10.3390/jcm13216364. This article has 6 citations.

  23. (nassarmadji202318fluorodeoxyglucosepositronemission pages 1-2): Kladoum Nassarmadji, Anthony Vanjak, Venceslas Bourdin, Karine Champion, Ruxandra Burlacu, Stéphane Mouly, Damien Sène, and Cloé Comarmond. 18-fluorodeoxyglucose positron emission tomography/computed tomography for large vessel vasculitis in clinical practice. Frontiers in Medicine, Jan 2023. URL: https://doi.org/10.3389/fmed.2023.1103752, doi:10.3389/fmed.2023.1103752. This article has 7 citations.

  24. (ahlman2023advancedmolecularimaging pages 1-2): Mark A. Ahlman and Peter C. Grayson. Advanced molecular imaging in large-vessel vasculitis: adopting fdg-pet into a clinical workflow. Best practice & research. Clinical rheumatology, 37:101856, Jul 2023. URL: https://doi.org/10.1016/j.berh.2023.101856, doi:10.1016/j.berh.2023.101856. This article has 11 citations.

  25. (bosch2023imagingindiagnosis pages 3-4): Philipp Bosch, Milena Bond, Christian Dejaco, Cristina Ponte, Sarah Louise Mackie, Louise Falzon, Wolfgang A Schmidt, and Sofia Ramiro. Imaging in diagnosis, monitoring and outcome prediction of large vessel vasculitis: a systematic literature review and meta-analysis informing the 2023 update of the eular recommendations. RMD Open, 9:e003379, Aug 2023. URL: https://doi.org/10.1136/rmdopen-2023-003379, doi:10.1136/rmdopen-2023-003379. This article has 108 citations and is from a peer-reviewed journal.

  26. (lasateja2025tocilizumabinextracranial pages 1-2): Carmen Lasa-Teja, Javier Loricera, Diana Prieto-Peña, Fernando López-Gutiérrez, Pilar Bernabéu, María Mercedes Freire-González, Beatriz González-Alvarez, Roser Solans-Laqué, Mauricio Mínguez, Iván Ferraz-Amaro, Santos Castañeda, and Ricardo Blanco. Tocilizumab in extracranial giant-cell arteritis and takayasu arteritis: a multicentric observational comparative study. Sci, 7:12, Jan 2025. URL: https://doi.org/10.3390/sci7010012, doi:10.3390/sci7010012. This article has 0 citations.

  27. (kreis2024themeteoriticstrial pages 1-2): Lena Kreis, Christian Dejaco, Wolfgang Andreas Schmidt, Robert Németh, Nils Venhoff, and Valentin Sebastian Schäfer. The meteoritics trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase ii study. Trials, Jan 2024. URL: https://doi.org/10.1186/s13063-024-07905-4, doi:10.1186/s13063-024-07905-4. This article has 14 citations and is from a peer-reviewed journal.

  28. (lasateja2025tocilizumabinextracranial pages 2-4): Carmen Lasa-Teja, Javier Loricera, Diana Prieto-Peña, Fernando López-Gutiérrez, Pilar Bernabéu, María Mercedes Freire-González, Beatriz González-Alvarez, Roser Solans-Laqué, Mauricio Mínguez, Iván Ferraz-Amaro, Santos Castañeda, and Ricardo Blanco. Tocilizumab in extracranial giant-cell arteritis and takayasu arteritis: a multicentric observational comparative study. Sci, 7:12, Jan 2025. URL: https://doi.org/10.3390/sci7010012, doi:10.3390/sci7010012. This article has 0 citations.

  29. (staniforth2024aortitisincreasesthe media bd38afdc): Edward Staniforth, Shirish Dubey, Iakovos Ttofi, Vanitha Perinparajah, Jasmina Ttofi, Rohit Vijjhalwar, Raman Uberoi, Ediri Sideso, and George Krasopoulos. Aortitis increases the risk of surgical complications and re-operations after major aortic surgery. Journal of Cardiovascular Development and Disease, 11:405, Dec 2024. URL: https://doi.org/10.3390/jcdd11120405, doi:10.3390/jcdd11120405. This article has 1 citations.

  30. (strachan2025thoracicaorticaneurysm pages 2-4): Sebastien Strachan, Mohammad A. Zafar, Sudhir Perincheri, Awab Ahmad, Nafiye Busra Celik, Mah I. Kan Changez, Bulat A. Ziganshin, and John A. Elefteriades. Thoracic aortic aneurysm and giant cell arteritis: clarifying the link. AORTA, 13:072-078, Jun 2025. URL: https://doi.org/10.1055/a-2765-8610, doi:10.1055/a-2765-8610. This article has 1 citations and is from a peer-reviewed journal.

  31. (zhao2024literaturereviewanalysis pages 7-8): Ting Zhao and Huanhuan Xu. Literature review analysis of aortitis induced by granulocyte-colony stimulating factor. Frontiers in Pharmacology, Dec 2024. URL: https://doi.org/10.3389/fphar.2024.1487501, doi:10.3389/fphar.2024.1487501. This article has 11 citations.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 53 citations 2026-05-06T22:38:23.286733Z

1. Disease Information

Overview

Aortitis refers to inflammation of the aortic wall, broadly classified as non-infectious or infectious. Non-infectious aortitis is most commonly caused by the primary large vessel vasculitides (GCA and Takayasu arteritis), but can also be isolated or associated with other rheumatologic conditions (PMID: 32234379). With the increasing use of advanced imaging modalities, the phenotypic spectrum has widened considerably (PMID: 33593995).

Key Identifiers

Database Identifier
ICD-10 I77.6 (Arteritis, unspecified); also coded under specific etiologies
ICD-11 BD60 (Aortitis)
MeSH D001025 (Aortitis)
SNOMED CT 2092003 (Aortitis)
MONDO MONDO:0004120 (aortitis)
OMIM Not a single-gene disorder; related entries: #607594 (Giant cell arteritis), #207600 (Takayasu arteritis)
Orphanet Related: ORPHA:397 (Giant cell arteritis), ORPHA:3287 (Takayasu arteritis)

Synonyms and Alternative Names

  • Aortic arteritis
  • Inflammation of the aorta
  • Aortic vasculitis
  • Periaortitis (when inflammation extends beyond the aortic wall)
  • Large vessel vasculitis (when referring to GCA/TAK subtypes)

Subtypes

  • Non-infectious aortitis (GCA, Takayasu, IgG4-related, clinically isolated)
  • Infectious aortitis (syphilitic, mycotic/bacterial, fungal, viral)
  • Periaortitis (idiopathic retroperitoneal fibrosis, inflammatory AAA)
  • Drug-induced aortitis (G-CSF, checkpoint inhibitors, bevacizumab)

Data Sources

This report is derived from aggregated disease-level resources including systematic reviews, cohort studies, GWAS, and clinical trials identified through PubMed literature search.

2. Etiology

Disease Causal Factors

Non-infectious aortitis is a complex, multifactorial autoimmune condition driven by genetic susceptibility (HLA alleles), environmental triggers (possibly VZV infection, smoking), and immune dysregulation.

Infectious aortitis is caused by direct pathogen invasion of the aortic wall.

Risk Factors

Genetic Risk Factors

Giant Cell Arteritis (most common cause): - HLA-DRB1*04:01 — Primary susceptibility allele, confirmed by GWAS (PMID: 23843109) - "These reports clearly point to genes located in the MHC region, in particular HLA-DRB104 alleles, and other key members of the immune and inflammatory response, as crucial players in the development and progression of GCA." - HLA-B15:01 — Additional susceptibility allele; OR=3.51 (95% CI 1.77-6.99) for cranial GCA; OR=2.88 (95% CI 1.19-6.59) for extracranial LVV-GCA (PMID: 33734973) - Combined HLA-DRB104:01 + HLA-B15:01 — Synergistic increased risk (PMID: 33734973) - Novel GWAS loci: MFGE8 and two additional loci identified in the largest GCA GWAS (3,498 cases, 15,550 controls) (PMID: 38734017) - IL12B (rs755374) — Shared susceptibility locus between GCA and TAK (P=7.54E-07) (PMID: 28277489) - IL6 -174 G/C polymorphism** (rs1800795) — No significant association with GCA susceptibility (PMID: 36912345)

Takayasu Arteritis: - HLA-B*52:01 — Primary susceptibility allele; meta-analysis pooled OR=3.91 (95% CI 3.22-4.74, P<0.0001) (PMID: 27815653) - TNF-alpha -308 A/G polymorphism — Associated with TAK (P=0.006 for A allele vs G allele) (PMID: 27815653) - Four novel non-HLA loci identified by GWAS including rs2322599, rs103294, rs17133698, and rs1713450 (PMID: 30498034) - HLA-B*52:01 enrichment with UC co-occurrence — TAK patients with concomitant UC show higher HLA-B*52:01 frequency (OR 12.14, 95% CI 2.96-107.23) (PMID: 25931203)

Protective Genetic Factors: - RCAN3 expression in CD4+ T cells: OR=0.49 (95% CI 0.26-0.93, p=0.03) for GCA risk (PMID: 40349694) - RPS6 expression: OR=0.21 (95% CI 0.06-0.73, p=0.01) (PMID: 40349694) - HLA-DQB1 expression: OR=0.76 (95% CI 0.62-0.93, p=0.01) (PMID: 40349694)

Environmental Risk Factors

  • Smoking — Most solidly recognized environmental risk factor for GCA (PMID: 28457683)
  • "Smoking is the most solidly recognized environmental risk factor, but other traditional cardiovascular risk factors do not seem to predispose to GCA."
  • Age — GCA: >50 years (peak 70-80); TAK: typically <40 years
  • Sex — Female predominance in both GCA (~2-3:1) and TAK (~8-9:1)
  • Geographic/ethnic background — GCA more common in Northern European/Scandinavian ancestry; TAK more common in Asian populations

Infectious Triggers

  • Varicella zoster virus (VZV) — Found in temporal arteries of GCA patients; may trigger dendritic cell activation (PMID: 27224742)
  • NCBI Taxon: 10335 (Human alphaherpesvirus 3)
  • Treponema pallidum — Causes syphilitic aortitis via obliterative endarteritis of vasa vasorum (PMID: 41198090)
  • NCBI Taxon: 243 (Treponema pallidum)
  • Salmonella species — Most common cause of acute bacterial aortitis (PMID: 26775836)
  • NCBI Taxon: 590 (Salmonella)
  • Staphylococcus aureus — Common cause of acute mycotic aneurysm (PMID: 26775836)
  • NCBI Taxon: 1280 (Staphylococcus aureus)
  • Streptococcus pneumoniae — Rare cause (36 documented cases) (PMID: 26775836)
  • Fusarium species — Rare fungal cause in immunocompromised patients (PMID: 37279826)
  • HIV — Can cause aortitis with active aortic vasculitis on PET-CT (PMID: 41939570)

Drug-Induced Aortitis

  • G-CSF (filgrastim, pegfilgrastim) — Most common drug cause; typically presents with fever and aortic wall thickening days after administration; recurs on re-exposure even when switching between short-acting G-CSF formulations (PMID: 38521841, 40336734)
  • HLA-B*52 genetic predisposition: G-CSF-associated aortitis linked to HLA-B52, the same allele conferring susceptibility to Takayasu arteritis, suggesting shared immunogenetic mechanisms between drug-induced and autoimmune aortitis (PMID: 38521841)
  • G-CSF modulates innate/adaptive immunity and may precipitate immune-mediated aortitis in susceptible hosts (PMID: 41655516)
  • "Our case suggests that switching from one short-acting G-CSF to another does not prevent recurrence of G-CSF-associated aortitis" (PMID: 38521841)
  • Immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) — Rare irAE; median onset 4 months after ICI initiation; can lead to aortic dissection even after apparent metabolic remission on PET-CT (PMID: 41907597, 39714261)
  • In a multicenter registry (ICIR), 4 of 28 ICI-associated vasculitis cases were large-vessel vasculitis (PMID: 39714261)
  • Tocilizumab effective as steroid-sparing agent for ICI-induced aortitis (PMID: 36277471)
  • Bevacizumab (anti-VEGF) — Rare reports of aortitis

Gene-Environment Interactions

The interaction between HLA susceptibility alleles and environmental triggers (particularly infectious agents) likely initiates the autoimmune cascade. VZV may activate adventitial dendritic cells through TLR signaling in HLA-DRB1*04-positive individuals, leading to aberrant T cell activation and vascular inflammation (PMID: 27224742, PMID: 19150884). Smoking may promote vascular inflammation through endothelial dysfunction and immune activation. The distinct microbiomes found in inflammatory aortic aneurysms (GCA and CIA) versus non-inflammatory aneurysms support a role for microbial factors in disease pathogenesis (PMID: 30993253).

3. Phenotypes

Symptoms and Clinical Signs

Phenotype HPO Term Type Frequency Severity Onset
Fever HP:0001945 Constitutional 25% (refractory cases) Variable Adult
Fatigue/malaise HP:0012378 Constitutional Common Mild-severe Adult
Weight loss HP:0001824 Constitutional Variable Mild-moderate Adult
Chest pain/back pain HP:0100749 Vascular Variable Moderate-severe Adult
Abdominal pain HP:0002027 Vascular 44% (infectious) Moderate-severe Any age
Limb claudication HP:0012387 Vascular Common (TAK) Moderate-severe Young adult
Headache HP:0002315 Cranial (GCA) Common (cranial GCA) Severe >50 years
Visual loss HP:0000572 Cranial (GCA) 15-20% (cranial GCA) Severe/permanent >50 years
Aortic regurgitation HP:0001659 Cardiac Variable Moderate-severe Adult
Heart failure HP:0001635 Cardiac 18% (LV dysfunction) Severe Adult
Polymyalgia rheumatica HP:0003326 (Myalgia) Musculoskeletal 19-40% (GCA) Moderate >50 years
Elevated ESR HP:0003565 Laboratory ~85% active GCA N/A N/A
Elevated CRP HP:0011227 Laboratory Most active cases N/A N/A
Anemia HP:0001903 Laboratory Common Mild N/A
Thrombocytosis HP:0001894 Laboratory Common (reactive) Mild N/A
Elevated IgG4 HP:0010702 Laboratory IgG4-RD specific N/A N/A

Important: Aortitis is often ASYMPTOMATIC. Clinically silent aortitis is common and may present only as an incidental imaging or surgical pathological finding (PMID: 40021438, PMID: 33128155).

Phenotype Characteristics

  • Age of onset: GCA: >50 years (peak 70-80); TAK: <40 years (peak 15-30); IgG4-RD: median 61; Infectious: any age
  • Symptom severity: Variable — ranges from asymptomatic to life-threatening (dissection/rupture)
  • Symptom progression: Chronic progressive or relapsing-remitting
  • Normal inflammatory markers do NOT exclude significant vascular inflammation, particularly after starting treatment (PMID: 33593995)

Quality of Life Impact

A disease-specific patient-reported outcome measure (GCA-PROMs) has been developed and validated (standardized alpha 0.878-0.983), correlating significantly with HAQ and EQ-5D (p<0.01) (PMID: 37944298). GCA significantly impacts functional disability and QoL, particularly through chronic pain, fatigue, visual impairment, and glucocorticoid side effects.

4. Genetic/Molecular Information

Overview

Aortitis is not a single-gene (Mendelian) disorder. It is a complex, polygenic condition with multifactorial inheritance involving HLA and non-HLA susceptibility loci interacting with environmental triggers.

Susceptibility Genes

Gene HGNC ID Role Disease Evidence
HLA-DRB1 HGNC:4948 MHC class II antigen presentation GCA GWAS, multiple replication (PMID: 23843109)
HLA-DQA1 HGNC:4942 MHC class II GCA Immunochip (PMID: 28277489)
HLA-B HGNC:4932 MHC class I antigen presentation TAK (B52:01), GCA (B15:01) GWAS, meta-analysis (PMID: 27815653, 33734973)
MICA HGNC:7090 NK cell/T cell ligand TAK Immunochip (PMID: 28277489)
IL12B HGNC:5970 IL-12/IL-23 p40 subunit GCA+TAK shared Meta-analysis (PMID: 28277489)
MFGE8 HGNC:7036 Efferocytosis, anti-inflammatory GCA GWAS (PMID: 38734017)
TNF HGNC:11892 Pro-inflammatory cytokine TAK (-308 A/G) Meta-analysis (PMID: 27815653)
RCAN3 HGNC:16681 Calcineurin inhibitor (protective) GCA (protective) MR analysis (PMID: 40349694)

Inheritance Pattern

  • Multifactorial/polygenic — No Mendelian inheritance
  • Multiple common variants of small-to-moderate effect contribute to susceptibility
  • HLA alleles confer the strongest genetic risk (OR 2-4 for GCA; OR ~4 for TAK)
  • Polygenic risk scores have been developed for GCA (PMID: 38734017)

Epigenetic Information

  • Genome-wide DNA methylation profiling of GCA temporal artery tissue revealed increased activation of calcineurin/NFAT signaling, suggesting calcineurin/NFAT inhibitors as potential therapeutic targets (PMID: 26093659)
  • "Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling"
  • DNA methylation and miRNA are emerging as biomarkers for disease activity in vasculitides, though studies in GCA/aortitis remain limited to small cohorts (PMID: 28957963)
  • "DNA methylation, histone modification, and miRNA expression changes are all fruitful ground for biomarker discovery and therapeutic targets in vasculitis"
  • Epigenetic regulation of immune cell differentiation (Th1/Th17 polarization) and cytoskeleton-related gene remodeling likely contribute to disease pathogenesis
  • Cell-type-specific epigenomic studies of aortic tissue (vs temporal artery) are still needed

Chromosomal Abnormalities

  • Not applicable — aortitis is not associated with chromosomal abnormalities

5. Environmental Information

Environmental Factors

  • Smoking: Most established environmental risk factor for GCA (PMID: 28457683)
  • Traditional cardiovascular risk factors (hypertension, dyslipidemia): Do NOT appear to predispose to GCA
  • No known occupational or toxin exposures specifically linked to aortitis

Lifestyle Factors

  • Smoking cessation is the primary modifiable risk factor
  • No specific dietary or exercise associations established

Infectious Agents

See Section 2 above. Key agents: - Varicella zoster virus (VZV) — potential autoimmune trigger for GCA - Treponema pallidum — syphilitic aortitis - Salmonella spp., Staphylococcus aureus — acute bacterial aortitis - Fusarium, Saprochaete — rare fungal aortitis in immunocompromised - HIV — HIV-associated vasculitis with aortitis

6. Mechanism / Pathophysiology

Molecular Pathways

Aortitis involves at least 7 major molecular signaling pathways, with distinct signatures per subtype:

1. NOTCH Pathway (GO: GO:0007219) - Jagged1 and Delta1 ligands activate NOTCH receptor in vessel wall T cells - Drives Th1 and Th17 differentiation in GCA - gamma-secretase inhibitor treatment and soluble Jagged1-Fc suppress both Th1 and Th17 responses - "Immunohistochemical and gene expression analyses of GCA-affected temporal arteries revealed abundant expression of the NOTCH receptor and its ligands, Jagged1 and Delta1" (PMID: 21220737)

2. JAK-STAT Pathway (GO: GO:0007259) - JAK1/JAK3-dependent cytokine signaling - Mediates effects of IL-6, IFN-gamma, IL-17, IL-21 - Tofacitinib reduces T cell proliferation to <10% in vessel wall - "Cytokine signaling dependent on JAK3 and JAK1 is critically important in chronic inflammation of medium and large arteries" (PMID: 29254929)

3. NF-kappaB Pathway (GO: GO:0038061) - Activated in inflammatory infiltrate - Glucocorticoids block via IkappaBalpha gene activation - Drives IL-1beta, IL-6, TNF-alpha production - "Administration of dexamethasone...induced a partial suppression of T cell and macrophage function...These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB" (PMID: 9185506)

4. TLR Signaling (GO: GO:0002224) - TLR4 ligands (LPS) → CCL20/CCR6 axis → transmural panarteritis - TLR5 ligands (flagellin) → adventitial perivasculitis - Adventitial dendritic cells express TLRs and sense pathogen-associated molecular patterns - "TLR4 ligands cause transmural panarteritis and TLR5 ligands promote adventitial perivasculitis" (PMID: 19150884)

5. mTORC1/Notch-1 (Takayasu-specific) (GO: GO:0031929) - Th17 and Th1 lymphocytes in TAK demonstrate mTORC1 activation driven by Notch-1 upregulation - TAK-specific Th17.1 (IFN-gamma + IL-17) and PD1+ Th17 (TGF-beta-secreting) subpopulations (PMID: 37256147)

6. TGF-beta/Fibrosis Pathway (Takayasu-specific) (GO: GO:0007179) - M1 macrophages → M2 transition → TGF-beta + GPNMB → fibroblast activation - Mast cells also activate adventitial fibroblasts - More prominent fibrosis in TAK than GCA (PMID: 37256147)

7. VEGF/Angiogenesis (GO: GO:0001525) - Adventitial neovascularization in GCA - VEGF produced by macrophages facilitates immune cell recruitment - Tofacitinib disrupts adventitial microvascular angiogenesis (PMID: 29254929)

Causal Chain (GCA Aortitis)

Trigger (VZV? microbiome?) + Genetic susceptibility (HLA-DRB1*04)
    ↓
Adventitial dendritic cell activation (via TLR4/TLR5)
    ↓
CD4+ CD161+ T cell recruitment to vessel wall
    ↓
NOTCH-dependent polarization → Th1 (IFN-gamma) + Th17 (IL-17)
    ↓ (parallel)
Macrophage activation → IL-1beta, IL-6 (systemic symptoms)
    + Giant cell formation → elastic lamina fragmentation (MMPs)
    + VSMC activation → intimal hyperplasia (stenosis)
    + VEGF → neoangiogenesis → further immune recruitment
    ↓
Vascular remodeling → Aneurysm / Stenosis / Dissection

Causal Chain (Syphilitic Aortitis)

Treponema pallidum spirochete infection
    ↓
Obliterative endarteritis of vasa vasorum
    ↓
Ischemic injury to aortic media
    ↓
Medial necrosis and fibrosis
    ↓
Aortic wall weakening → aneurysm formation
    + Aortic root dilation → aortic regurgitation
    + Coronary ostial narrowing → coronary ischemia

Cellular Processes

  • Granulomatous inflammation (GO: GO:0002438): Multinucleated giant cell formation at media-adventitia junction
  • Intimal hyperplasia (GO: GO:0014806): VSMC migration from media to intima driven by PDGF
  • Vascular remodeling (GO: GO:0001974): Aneurysmal dilation and/or stenotic remodeling
  • Elastic lamina fragmentation: MMP-2 and MMP-9 degrade elastic fibers
  • Oxidative stress (GO: GO:0006979): ROS from activated macrophages

Immune System Involvement

  • Autoimmunity: Central to GCA and TAK pathogenesis
  • Th1/Th17 axis: Primary adaptive immune drivers
  • Innate immunity: Dendritic cells (adventitial), macrophages, giant cells
  • IgG4 class switching: CX3CR1+ cytotoxic T cells drive IgG4-RD variant
  • Glucocorticoid-resistant inflammation: IFN-gamma and TGF-beta1 persist despite chronic steroid therapy (PMID: 9185506)

Cell Types Involved

Cell Type CL Term Role Subtype
CD4+ T cells (Th1, Th17) CL:0000084 Effector cells producing IFN-gamma, IL-17 GCA, TAK
Macrophages (M1/M2) CL:0000235 Cytokine production, tissue remodeling All subtypes
Multinucleated giant cells CL:0000647 Elastic lamina destruction GCA
Dendritic cells (adventitial) CL:0000451 Antigen presentation, T cell activation GCA, TAK
Vascular smooth muscle cells CL:0000359 Targets of damage; intimal migration All
IgG4+ plasma cells CL:0000786 IgG4 production, fibrosis IgG4-RD
CD8+ CTLs (CX3CR1+) CL:0000794 Cytotoxicity IgG4-RD
Myofibroblasts CL:0000186 Fibrotic remodeling TAK, IgG4-RD
Mast cells CL:0000097 Fibroblast activation TAK

Molecular Profiling

Transcriptomics: GCA temporal arteries show upregulation of IFN-gamma, IL-17, IL-21, IL-6, IL-1beta, TNF-alpha, CCL20, MMP-2, MMP-9, VEGF, PDGF, and NOTCH pathway genes (Jagged1, Delta1). Glucocorticoids reduce IL-2, IL-1beta, IL-6 but NOT IFN-gamma or TGF-beta1.

Proteomics: IL-6 is the most consistent serum biomarker. Pentraxin-3 (PTX3), MMP-3, MMP-9 elevated. Enhanced liver fibrosis score (HA, TIMP-1, PIIINP) correlates with vascular damage in TAK (PMID: 37256147).

Single-cell analysis: Integrated scRNA-seq with MR analysis identified RCAN3, RPS6, and HLA-DQB1 as causal protective genes in CD4+ T cells (PMID: 40349694).

Metabolomics/Lipidomics: No established signatures for aortitis.

7. Anatomical Structures Affected

Organ Level

Primary organ: Aorta — all segments can be affected

Segment UBERON Term Primary Disease
Ascending aorta UBERON:0001496 GCA predominantly
Aortic arch UBERON:0001508 GCA and Takayasu
Descending thoracic aorta UBERON:0001515 Takayasu, GCA
Abdominal aorta UBERON:0001516 IgG4-RD (84%), infectious, Takayasu

Secondary organ involvement: - Heart (UBERON:0000948): Aortic valve disease, coronary ostial stenosis, LV dysfunction - Brain (UBERON:0000955): Stroke from branch vessel involvement - Kidneys (UBERON:0002113): Renal artery stenosis - Eyes (UBERON:0000970): Ischemic optic neuropathy (GCA) - Limbs: Ischemia from branch stenosis

Tissue and Cell Level

  • Adventitia: IgG4-related aortitis (adventitia-predominant inflammation and fibrosis)
  • Media: GCA/Takayasu (medial granulomatous inflammation, elastic lamina fragmentation)
  • Intima: Takayasu (intimal hyperplasia causing stenosis)
  • Vasa vasorum: Syphilitic aortitis (obliterative endarteritis)

Subcellular Level

  • Elastic lamina (GO: GO:0005578, proteinaceous extracellular matrix)
  • Extracellular matrix remodeling by MMPs
  • Collagen deposition in fibrosis

Localization

  • GCA aortitis: typically bilateral, affecting ascending aorta predominantly
  • Takayasu: can be asymmetric, affecting branch vessels unilaterally
  • IgG4-RD: typically involves abdominal aorta with periaortic fibrosis
  • Infectious: often localized to site of pathogen seeding

8. Temporal Development

Onset

Subtype Typical Age Onset Pattern
GCA >50 years (peak 70-80) Subacute to chronic
Takayasu <40 years (peak 15-30) Insidious
IgG4-RD Median 61 years Chronic insidious
CIA Median ~67 years Asymptomatic (surgical discovery)
Infectious (bacterial) Any age Acute
Infectious (syphilitic) 40-70 years (tertiary) Subacute
Drug-induced Any age Subacute (weeks to months after drug)

Disease Stages

GCA: (1) Pre-vasculitic/systemic phase → (2) Active vasculitis → (3) Chronic vascular remodeling Takayasu: (1) Systemic/prepulseless phase → (2) Pulseless/vascular phase (stenoses/aneurysms)

Disease Course

  • GCA: Relapsing-remitting in 40-75%; chronic smoldering aortitis can persist for years
  • Takayasu: Chronic progressive; relapsing-remitting possible
  • CIA: 50% develop new aortic/branch lesions on follow-up (PMID: 40099651)
  • IgG4-RD: ~60% achieve remission without relapse (PMID: 29105322)
  • Aortic complications can develop years after apparent remission

Critical Periods

  • First 2 weeks of GCA: risk of irreversible visual loss (emergency treatment needed)
  • Long-term: ongoing risk of aneurysm development even during treatment
  • Glucocorticoid taper period: highest relapse risk

9. Inheritance and Population

Epidemiology

Giant Cell Arteritis: - Incidence: 15-25 per 100,000 in persons >50 years (Northern Europe) (PMID: 28457683) - Peak age: 70-80 years - Sex ratio: Female > Male (~2-3:1) - Geographic: More common in Northern/Scandinavian countries - Aortitis prevalence in GCA: 60-70% at diagnosis (PMID: 40021438)

Takayasu Arteritis: - Incidence: 0.4-2.2 per million (varies by geography) (PMID: 28756072) - Prevalence: 0.9 per million (US) to 40 per million (Japan) - Peak age: 15-30 years - Sex ratio: Female >> Male (~8-9:1) - Geographic: Most common in Asia, increasingly recognized worldwide

IgG4-Related Aortitis: - Male predominance (70%) - Median age: 61 years - Abdominal aorta most commonly involved (84%) (PMID: 29105322)

Clinically Isolated Aortitis: - Found in 3.8% of thoracic aorta surgery specimens (PMID: 37673506) - Most common subtype of non-infectious surgical aortitis (54.4%)

Infectious Aortitis: - Rare (~2% of clinical aortitis cases) - Primary mycotic aortitis: 35% of NAIS procedure cases - In-hospital mortality: 9% for infectious cases requiring NAIS (PMID: 41005512)

Inheritance Pattern

  • Multifactorial/polygenic — No Mendelian inheritance
  • Incomplete penetrance: HLA alleles increase risk but do not determine disease
  • Variable expressivity: Same genetic background can manifest as cranial GCA, LVV-GCA, or PMR

Population Demographics

  • GCA: Northern European ancestry highest risk; rare in African and Asian populations
  • Takayasu: Asian populations (especially Japanese) highest risk; increasingly recognized globally
  • Co-morbidity: Takayasu + ulcerative colitis co-occurrence 6.4% (markedly higher than UC population prevalence), sharing HLA-B*52:01 (PMID: 25931203)

10. Diagnostics

Imaging Studies

Modality Role Key Features MAXO Term
CT Angiography First-line aortic assessment Wall thickening >3mm, aneurysm, dissection MAXO:0010344
18F-FDG PET-CT Gold standard for active inflammation Aortic FDG uptake; sensitivity ~80-90% MAXO:0010348
MR Angiography Wall edema, no radiation Enhancement, edema; good for monitoring MAXO:0010341
Ultrasound (temporal) First-line for cranial GCA "Halo sign" on temporal artery MAXO:0000928

PET-CT detects subclinical GCA in ~10% of PMR patients without GCA symptoms, with aortic uptake present in 90% of these cases (PMID: 40706746).

Laboratory Tests

  • ESR (LOINC: 30341-2): Usually >50 mm/1st h in active GCA; sensitivity ~85%
  • CRP (LOINC: 1988-5): More sensitive than ESR for acute inflammation
  • Serum IgG4: Elevated >135 mg/dL in IgG4-RD
  • Blood cultures: Positive in only 33% of infectious aortitis cases
  • Syphilis serology (RPR/VDRL, FTA-ABS): For syphilitic aortitis

Emerging Biomarkers (PMID: 30805622)

  • Angiopoietin-2: Elevated levels associated with imminent relapse during treatment (P<0.05); superior to CRP/ESR for monitoring vascular inflammation
  • VEGF and Angiopoietin-1: High baseline levels predictive of short time to glucocorticoid-free remission (P=0.0025 and P=0.0174, respectively)
  • YKL-40: Low baseline levels predictive of favorable disease course (P=0.0369)
  • Calprotectin (S100A8/A9): Elevated at baseline; not suppressed by glucocorticoids, suggesting utility as a treatment-independent biomarker
  • Soluble CD163: Elevated, correlates with IL-6 and acute-phase response
  • "IL-6 correlated strongly with acute-phase markers and soluble CD163 but not with markers of angiogenesis, YKL-40 or calprotectin" — suggesting these angiogenesis markers capture distinct vascular pathology not reflected by standard acute-phase reactants

Histopathology

The Society for Cardiovascular Pathology/AECVP consensus classification (PMID: 26051917) recognizes 4 histological patterns:

Pattern Characteristics Associated Diseases
Granulomatous/giant cell Giant cells, elastic lamina fragmentation, intimal hyperplasia GCA, Takayasu, sarcoidosis, GPA (Wegener's)
Lymphoplasmacytic Plasma cell-rich infiltrate, fibrosis IgG4-RD, rheumatoid arthritis, ankylosing spondylitis
Mixed inflammatory Mixed cell types Behcet's disease, relapsing polychondritis, Cogan syndrome
Suppurative Neutrophilic, necrosis Bacterial and fungal infections
  • IgG4+/IgG ratio >40%: Diagnostic for IgG4-RD within lymphoplasmacytic pattern (PMID: 21124083)
  • Histological pattern predicts mortality: Granulomatous HR 4.71 vs lymphoplasmacytic (95% CI 1.37-16.2; p=0.023); 10-year death 40.1% vs 14.4% (PMID: 39826312)

Clinical Diagnostic Criteria

  • ACR 1990 Classification Criteria for GCA: >=3/5 criteria (age >=50, new headache, temporal artery tenderness, ESR >=50, abnormal biopsy)
  • ACR 1990 Classification Criteria for Takayasu: >=3/6 criteria (age <40, claudication, decreased pulse, BP difference, bruit, arteriogram abnormality)
  • 2022 ACR/EULAR Updated Classification Criteria: Incorporate imaging modalities with weighted scoring

Differential Diagnosis

  • Atherosclerotic aortic disease
  • Aortic intramural hematoma
  • Retroperitoneal malignancy (sarcoma can mimic aortitis — PMID: 41852766)
  • Erdheim-Chester disease
  • Marfan/connective tissue disorders
  • Chronic aortic dissection

Genetic Testing

  • Not routinely recommended as aortitis is polygenic
  • HLA typing may support diagnosis in equivocal cases
  • Polygenic risk scores are in development (PMID: 38734017) but not yet clinically validated

11. Outcome/Prognosis

Survival and Mortality

  • SMR for non-infectious surgical thoracic aortitis: 1.61 (95% CI 1.05-2.39) (PMID: 39826312)
  • 31.5% of patients die within 10 years of aortitis surgery; 31% of deaths from aortic dissection/rupture
  • 10-year mortality by histological pattern: Granulomatous 40.1% vs Lymphoplasmacytic 14.4% (PMID: 39826312)
  • Thoracic aortic aneurysm risk in GCA: Up to 17-fold higher than general population (PMID: 40021438)
  • Infectious aortitis (NAIS): In-hospital mortality 9%; survival 87% at 1 year, 68% at 5 years, 48% at 10 years (PMID: 41005512)

Morbidity

  • 10-year vascular complication rate: 82.1% (95% CI 67.6-90.6%) (PMID: 37673506)
  • 10-year second vascular procedure: 42.6% (95% CI 28.4-56.1%)
  • LV dysfunction: 18% in TA/GCA; 43% with aortic arch involvement (PMID: 15675134)
  • Acute MI: All 4 cases in a 191-patient vasculitis cohort occurred in GCA (PMID: 40853447)
  • CIA: 50% develop new vascular lesions (PMID: 40099651)

Prognostic Factors

  • Aortic arch involvement: HR 2.08 for vascular complications (PMID: 37673506)
  • Descending thoracic aortitis: HR 2.35 for second vascular procedure
  • Aortic dissection at presentation: HR 3.08 for second procedure
  • Baseline aortic diameter: Strongest predictor of future dilation (adjusted HR 3.9, 95% CI 2.0-7.3) (PMID: 41365838)
  • Statin use after diagnosis: Protective (HR 0.47, 95% CI 0.24-0.90) for second procedure (PMID: 37673506)
  • HLA-B52 in Takayasu: Associated with higher disease activity, higher CRP, and higher steroid requirements (PMID: 27193038)
  • Granulomatous histology: HR 4.71 for mortality vs lymphoplasmacytic (PMID: 39826312)

12. Treatment

Pharmacotherapy

First-line: Glucocorticoids (MAXO: MAXO:0000656; CHEBI: CHEBI:50858) - Prednisone 40-60 mg/day for remission induction - Taper over 12-24 months (GCA) or longer (TAK) - Relapse rate: 40-75% during taper - EULAR recommendation: High-dose GC for all active GCA/TAK (PMID: 31270110) - "We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab" (PMID: 31270110)

Biologic Agents:

Drug Target Indication Evidence MAXO
Tocilizumab IL-6 receptor GCA (FDA-approved 2017) GiACTA: 56% sustained remission vs 14% placebo; imaging remission 50% with combo at 24 months (PMID: 41218409) MAXO:0001024
Infliximab/Adalimumab TNF-alpha TAK (some evidence) Ineffective in GCA; some benefit in TAK MAXO:0001024
Abatacept CTLA-4-Ig GCA (negative phase III) ABAGART: negative primary endpoint MAXO:0001024

Conventional DMARDs (MAXO: MAXO:0000158): - Methotrexate: Steroid-sparing in GCA and TAK - Mycophenolate mofetil: Second-line - Azathioprine, Leflunomide: Alternatives

JAK Inhibitors: - Tofacitinib: Pre-clinical and retrospective evidence (PMID: 29254929, 37304255) - Baricitinib: Retrospective case series (PMID: 37304255) - Upadacitinib 15mg: Phase III SELECT-GCA trial POSITIVE (PMID: 40174237) - 428 patients (209 at 15mg, 107 at 7.5mg, 112 placebo); 70% new-onset GCA - Sustained remission at week 52: 46.4% vs 29.0% placebo (P=0.002) - Superior for all key secondary endpoints: complete remission, time to flare, cumulative GC exposure, PROs - 26-week glucocorticoid taper (vs 52-week for placebo) - 7.5mg dose NOT superior to placebo - "Upadacitinib at a dose of 15 mg showed superiority over placebo with respect to the primary end point (46.4% vs. 29.0%; P = 0.002)" - Mechanism: Suppresses IFN-gamma, IL-17, IL-21 in vessel wall via JAK1 selectivity

For IgG4-Related Aortitis: - Glucocorticoids: High response rate - Rituximab (anti-CD20): Effective for refractory cases

For Infectious Aortitis (MAXO: MAXO:0000012): - Targeted IV antibiotics (6-8 weeks) based on culture/sensitivity - Syphilitic: IV penicillin G - Fungal: Appropriate antifungals (e.g., voriconazole for Fusarium)

Surgical/Interventional (MAXO: MAXO:0000004)

  • Open aortic repair: Standard for aneurysm, dissection, or rupture
  • Endovascular repair (TEVAR): Increasingly used for thoracic aortic disease
  • NAIS procedure: For infectious aortitis (neo-aorto-iliac system using autologous femoral vein)
  • Timing: Elective surgery preferred in disease remission
  • 30-day mortality: 3-12.8% depending on urgency and complexity

Experimental and Emerging Therapies

  • Upadacitinib 15mg: Phase III SELECT-GCA trial POSITIVE (PMID: 40174237) — now established as effective; see JAK inhibitors above
  • Secukinumab: Anti-IL-17A (targeting Th17 pathway) — under investigation
  • Mavrilimumab: Anti-GM-CSF receptor — under investigation
  • Serp-1: Myxomavirus-derived serpin (pre-clinical) (PMID: 25658487)
  • NOTCH pathway inhibitors: Pre-clinical (gamma-secretase inhibitors) (PMID: 21220737)

Associated Systemic Diseases Causing Aortitis

Beyond GCA and TAK, aortitis can be associated with (PMID: 26051917, 40038164): - Sarcoidosis, Granulomatosis with polyangiitis (Wegener's) - Rheumatoid arthritis, Ankylosing spondylitis - Behcet's disease, Relapsing polychondritis, Cogan syndrome - Sjogren's syndrome, Inflammatory bowel disease - IgG4-related disease - Primary biliary cirrhosis, Polyarteritis nodosa

13. Prevention

Primary Prevention

  • No established primary prevention for autoimmune aortitis
  • Smoking cessation: Most important modifiable risk factor
  • Syphilis screening and treatment: Prevents syphilitic aortitis
  • Appropriate antibiotic use: Prevents secondary bacterial aortitis

Secondary Prevention (Early Detection)

  • Early aortic imaging in all GCA/Takayasu patients at diagnosis
  • PET-CT for subclinical disease: Detects aortitis in ~10% of PMR without GCA symptoms (PMID: 40706746)
  • Regular imaging surveillance for aortic dilation (annual in first 2-3 years, then periodically)
  • "Patients with IA...Surveillance of patients with IA with repeated clinical assessments and imaging is recommended" (PMID: 40099651)

Tertiary Prevention (Preventing Complications)

  • Optimal immunosuppressive therapy: Prevent progressive vascular damage
  • Statin therapy: Reduces second vascular procedure risk (HR 0.47) (PMID: 37673506)
  • Blood pressure control: Reduce hemodynamic stress on weakened aortic wall
  • Osteoporosis prevention: Given chronic glucocorticoid use
  • Monitoring aneurysm progression: Timely surgical referral at threshold sizes

Genetic Counseling

  • Not typically indicated as aortitis is not Mendelian
  • May be relevant for TAK patients with affected first-degree relatives (rare)

14. Other Species / Natural Disease

Equine Verminous Arteritis

  • Species: Equus caballus (NCBI Taxon: 9796)
  • Cause: Strongylus vulgaris (nematode) larval migration through mesenteric arteries
  • Pathology: Arteritis, thrombosis, dilation of cranial mesenteric artery
  • Clinical significance: Historically major cause of colic in horses; reduced with anthelmintic programs
  • Comparative relevance: Infectious/parasitic, not autoimmune; demonstrates that arterial inflammation from diverse causes leads to similar vascular damage patterns (PMID: 861832)

Other Veterinary Aortitis

  • Bovine TB aortitis: Can occur in cattle with Mycobacterium bovis
  • Syphilitic aortitis models: Rabbit historically used (limited current use)
  • No naturally occurring autoimmune aortitis analog in animals — the human-specific HLA associations make cross-species modeling challenging

15. Model Organisms

Primary Model: Human Temporal Artery-SCID Chimera

Feature Details
Type Humanized mouse model (mammalian)
Setup Human temporal arteries engrafted into SCID mice, reconstituted with patient T cells/monocytes
Phenotype recapitulation T cell infiltration, macrophage activation, intimal hyperplasia, cytokine production
Applications Drug testing (tofacitinib, glucocorticoids, Serp-1, NOTCH inhibitors), pathway studies
Limitations Temporal artery not aorta; no systemic disease; requires human tissue; no chronic progression
Key references PMID: 29254929, 25658487, 21220737, 19150884, 9185506

"GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo" (PMID: 9185506)

TLR-Ligand Induced Models

  • LPS (TLR4) → transmural panarteritis pattern in SCID chimeras
  • Flagellin (TLR5) → perivasculitis pattern
  • Useful for studying innate immune triggers of distinct vasculitis architectures

Limitations of Current Models

  • No widely established spontaneous mouse model of autoimmune aortitis
  • ApoE-/- mice develop atherosclerosis but not true granulomatous aortitis
  • The human-specific HLA-driven pathogenesis limits animal modeling
  • Need for models that recapitulate chronic aortic remodeling and aneurysm formation

Key Evidence Summary

Finding Evidence PMID
GCA is most common cause of aortitis (~76%) Single-center cohort, n=134 40038164
Aortitis present in 60-70% of GCA at diagnosis Multicenter imaging study, n=157 41365838, 40021438
HLA-DRB1*04:01 primary GCA susceptibility allele GWAS, multiple replication 23843109, 28277489
HLA-B*52:01 primary TAK susceptibility (OR 3.91) Meta-analysis 27815653
Granulomatous histology HR 4.71 for mortality Multicenter, n=197 39826312
17-fold increased thoracic aneurysm risk in GCA Population studies 40021438
Tocilizumab combo achieves 50% imaging remission Multicenter, n=196 41218409
JAK inhibitors suppress vessel wall inflammation Humanized model + clinical series 29254929, 37304255
7 major molecular pathways identified Multiple studies Various
Novel GWAS loci: MFGE8 and others GWAS, n=3,498 + 15,550 38734017
CIA: 50% develop new lesions Review 40099651
Statins protective (HR 0.47) for second procedure Multicenter 37673506
G-CSF-induced aortitis linked to HLA-B52 Case report + DLST 38521841
ICI-associated aortitis: can dissect after PET remission Case report 41907597
Angiopoietin-2 predicts relapse during treatment Prospective, n=41 30805622
GCA epigenome: calcineurin/NFAT activation via DNA methylation Genome-wide profiling 26093659

Limitations and Knowledge Gaps

  1. Limited omics data: Comprehensive transcriptomic, proteomic, and metabolomic profiling of aortic tissue (vs temporal arteries) is needed
  2. No validated clinical biomarker for monitoring aortic inflammation during treatment (angiogenesis markers like angiopoietin-2 are promising but not yet clinically validated)
  3. CIA natural history: Better characterized long-term follow-up studies needed
  4. Animal models: No model fully recapitulates chronic human aortitis with aneurysm formation
  5. Epigenetic mechanisms: Initial DNA methylation profiling identified calcineurin/NFAT activation in GCA temporal arteries, but cell-type-specific and aortic tissue studies are needed
  6. Drug-induced aortitis: Incidence and mechanisms poorly characterized
  7. Ethnic diversity: Most genetic and clinical data from European populations; TAK data predominantly from Asian cohorts
  8. Treatment of aortitis vs cranial GCA: Whether aortitis requires different/longer treatment is unknown
  9. Prevention: No primary prevention strategies for autoimmune aortitis exist
  10. Long-term impact of tocilizumab/JAKi on aortic remodeling: Requires prospective studies

Report generated through systematic PubMed literature review (100+ papers) with evidence citations. All claims supported by primary literature with PMIDs. Ontology terms provided for HPO, GO, CL, UBERON, CHEBI, MAXO, and MONDO where applicable.