A rare anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis characterized by necrotizing granulomatous inflammation of small and medium vessels (capillaries, venules, and arterioles), resulting in tissue ischemia. Strongly associated with anti-PR3 (c-ANCA) antibodies. The classic triad involves the upper respiratory tract, lungs, and kidneys, though any organ may be affected. Formerly known as Wegener's granulomatosis.
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name: Granulomatosis with Polyangiitis
creation_date: '2025-12-19T01:12:52Z'
updated_date: '2026-05-01T18:00:00Z'
category: Autoimmune
parents:
- Autoimmune Disease
- Vasculitis
disease_term:
preferred_term: Granulomatosis with Polyangiitis
term:
id: MONDO:0012105
label: granulomatosis with polyangiitis
description: >-
A rare anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis
characterized by necrotizing granulomatous inflammation of small and medium
vessels (capillaries, venules, and arterioles), resulting in tissue ischemia.
Strongly associated with anti-PR3 (c-ANCA) antibodies. The classic triad involves
the upper respiratory tract, lungs, and kidneys, though any organ may be affected.
Formerly known as Wegener's granulomatosis.
pathophysiology:
- name: B Cell Autoreactivity and ANCA Production
description: >-
Autoreactive B cells produce anti-proteinase 3 (PR3-ANCA) antibodies,
the defining upstream event in GPA pathogenesis. Genetic predisposition
(HLA-DP alleles) and environmental triggers (S. aureus, silica) drive
loss of tolerance to PR3, leading to sustained autoantibody production.
cell_types:
- preferred_term: B cell
term:
id: CL:0000236
label: B cell
biological_processes:
- preferred_term: B Cell Activation
term:
id: GO:0042113
label: B cell activation
evidence:
- reference: PMID:39257888
reference_title: "Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis."
supports: SUPPORT
snippet: >-
Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized
by granulomatous inflammation of the respiratory tract and necrotizing
vasculitis of small and medium vessels often associated with the production of
anti-neutrophil cytoplasmic antibodies (ANCA) directed mainly against leukocyte
proteinase 3 (PR3).
explanation: >-
Confirms that GPA is defined by production of ANCA directed against PR3,
establishing B cell-mediated autoantibody production as the upstream event.
- reference: PMID:36315063
reference_title: "Diagnosing and treating ANCA-associated vasculitis: an updated review for clinical practice."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Exposure to silica
dust, farming and chronic nasal Staphylococcus aureus carriage are associated
with increased risk of developing AAV.
explanation: >-
Environmental triggers (silica, S. aureus) contribute to loss of B cell
tolerance and ANCA production.
downstream:
- target: ANCA-Mediated Neutrophil Activation
- name: ANCA-Mediated Neutrophil Activation
description: >-
Anti-proteinase 3 (PR3) antibodies bind to primed neutrophils, causing
activation, degranulation, and release of reactive oxygen species and
lytic enzymes. This causes direct endothelial damage and vessel wall
necrosis. Neutrophil extracellular trap (NET) formation further amplifies
vascular injury.
cell_types:
- preferred_term: Neutrophil
term:
id: CL:0000775
label: neutrophil
- preferred_term: Endothelial Cell
term:
id: CL:0000115
label: endothelial cell
biological_processes:
- preferred_term: Neutrophil Activation
term:
id: GO:0042119
label: neutrophil activation
- preferred_term: Neutrophil Extracellular Trap Formation
term:
id: GO:0140645
label: neutrophil extracellular trap formation
evidence:
- reference: PMID:37781373
reference_title: The involvement of NETs in ANCA-associated vasculitis.
supports: SUPPORT
snippet: >-
The pathogenesis of AAV includes ANCA-mediated neutrophil activation,
subsequent release of inflammatory cytokines and reactive oxygen species (ROS),
and formation of neutrophil extracellular traps (NETs).
explanation: >-
This review confirms that ANCA-mediated neutrophil activation is a central
pathogenic mechanism in AAV, leading to ROS release and NET formation.
- reference: PMID:38791316
reference_title: Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.
supports: SUPPORT
snippet: >-
Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation,
and neutrophil extracellular trap (NETs) formation are discussed, along with
the
role of the complement system in inducing pulmonary injury.
explanation: >-
Confirms neutrophil activation and NET formation as key mechanisms in
pulmonary injury in GPA.
downstream:
- target: Granuloma Formation
- target: Complement Alternative Pathway Activation
- name: Granuloma Formation
description: >-
Granulomatous inflammation with multinucleated giant cells, epithelioid
macrophages, and necrosis affects the respiratory tract. CD4+ T cells and
macrophages organize into granulomas that destroy tissue, a hallmark
distinguishing GPA from other ANCA-associated vasculitides.
cell_types:
- preferred_term: Macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: CD4-positive T cell
term:
id: CL:0000624
label: CD4-positive, alpha-beta T cell
biological_processes:
- preferred_term: Granuloma Formation
term:
id: GO:0002432
label: granuloma formation
- preferred_term: Inflammatory Response
term:
id: GO:0006954
label: inflammatory response
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002955 | Granulomatosis | Very frequent (99-80%)"
explanation: >-
Orphanet classifies granulomatosis as a very frequent feature of GPA,
consistent with granuloma formation being a hallmark pathological process.
- reference: PMID:39257888
supports: SUPPORT
snippet: >-
Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized
by granulomatous inflammation of the respiratory tract and necrotizing
vasculitis of small and medium vessels
explanation: >-
Confirms granulomatous inflammation of the respiratory tract as a defining
feature of GPA.
- name: Complement Alternative Pathway Activation
description: >-
The alternative complement pathway amplifies inflammation in GPA.
C5a recruits and activates neutrophils, creating a positive feedback
loop of vascular damage. This mechanism is the therapeutic target of
avacopan (C5a receptor inhibitor).
biological_processes:
- preferred_term: Complement Activation
term:
id: GO:0006956
label: complement activation
evidence:
- reference: PMID:37781373
reference_title: The involvement of NETs in ANCA-associated vasculitis.
supports: SUPPORT
snippet: >-
Mechanistically, cytokines or complement factors activate and prime neutrophils
for ANCA-binding; thus, C5a receptor blocker has garnered attention as potential
replacement for glucocorticoids in clinical settings.
explanation: >-
Confirms complement factors prime neutrophils for ANCA binding, and that
C5a receptor blockade is a validated therapeutic target.
- reference: PMID:38791316
reference_title: Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.
supports: SUPPORT
snippet: >-
Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation,
and neutrophil extracellular trap (NETs) formation are discussed, along with
the
role of the complement system in inducing pulmonary injury.
explanation: >-
Confirms the complement system plays a role in amplifying
ANCA-mediated pulmonary injury.
phenotypes:
# === ENT / Upper Respiratory ===
- name: Sinusitis
category: ENT
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Sinusitis
term:
id: HP:0000246
label: Sinusitis
temporality: CHRONIC
notes: >-
Chronic destructive sinusitis is one of the most common presenting features,
often with bloody or purulent nasal discharge.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000246 | Sinusitis | Very frequent (99-80%)"
explanation: Orphanet classifies sinusitis as very frequent in GPA.
- reference: PMID:28881446
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In GPA, the most common disease features at diagnosis were
otorhinolaryngological (74%), followed by "general" (57%) and pulmonary (48%)
manifestations.
explanation: >-
Olmsted County cohort confirms ENT manifestations (including sinusitis)
as the most common presenting feature of GPA at 74%.
- name: Epistaxis
category: ENT
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Epistaxis
term:
id: HP:0000421
label: Epistaxis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000421 | Epistaxis | Very frequent (99-80%)"
explanation: Orphanet classifies epistaxis as very frequent in GPA.
- name: Nasal Septum Perforation
category: ENT
frequency: OCCASIONAL
phenotype_term:
preferred_term: Nasal septum perforation
term:
id: HP:0033434
label: Nasal septum perforation
notes: Due to granulomatous destruction of nasal cartilage and septum.
- name: Saddle Nose Deformity
category: ENT
frequency: OCCASIONAL
phenotype_term:
preferred_term: Saddle Nose Deformity
term:
id: HP:0005280
label: Depressed nasal bridge
notes: Due to nasal cartilage destruction from granulomatous inflammation.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000366 | Abnormality of the nose | Very frequent (99-80%)"
explanation: >-
Orphanet reports nasal abnormalities as very frequent; saddle nose deformity
from cartilage destruction is a classic late finding.
- name: Otitis Media
category: ENT
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Otitis media
term:
id: HP:0000388
label: Otitis media
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000388 | Otitis media | Very frequent (99-80%)"
explanation: Orphanet classifies otitis media as very frequent in GPA.
- name: Sensorineural Hearing Impairment
category: ENT
frequency: OCCASIONAL
phenotype_term:
preferred_term: Sensorineural hearing impairment
term:
id: HP:0000407
label: Sensorineural hearing impairment
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000407 | Sensorineural hearing impairment | Occasional (29-5%)"
explanation: Orphanet classifies sensorineural hearing loss as occasional in GPA.
- name: Subglottic Stenosis
category: ENT
frequency: OCCASIONAL
phenotype_term:
preferred_term: Subglottic stenosis
term:
id: HP:0001607
label: Subglottic stenosis
notes: Can cause stridor and airway compromise; may require surgical intervention.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0001607 | Subglottic stenosis | Occasional (29-5%)"
explanation: Orphanet classifies subglottic stenosis as occasional in GPA.
- name: Oral Cavity Abnormality
category: ENT
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Oral cavity abnormality
term:
id: HP:0000163
label: Abnormal oral cavity morphology
notes: Includes strawberry gingivitis, oral ulcers, and palatal perforation.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000163 | Abnormal oral cavity morphology | Very frequent (99-80%)"
explanation: Orphanet classifies oral cavity abnormalities as very frequent in GPA.
# === Pulmonary ===
- name: Recurrent Respiratory Infections
category: Respiratory
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Recurrent respiratory infections
term:
id: HP:0002205
label: Recurrent respiratory infections
notes: >-
Reflects mucociliary dysfunction and mucosal destruction from chronic
sinonasal granulomatous disease.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002205 | Recurrent respiratory infections | Very frequent (99-80%)"
explanation: Orphanet classifies recurrent respiratory infections as very frequent in GPA.
- name: Pulmonary Infiltrates
category: Respiratory
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Pulmonary infiltrates
term:
id: HP:0002113
label: Pulmonary infiltrates
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002113 | Pulmonary infiltrates | Very frequent (99-80%)"
explanation: Orphanet classifies pulmonary infiltrates as very frequent in GPA.
- name: Pulmonary Nodules
category: Respiratory
frequency: OCCASIONAL
phenotype_term:
preferred_term: Pulmonary nodule
term:
id: HP:0033608
label: Pulmonary nodule
notes: May cavitate; cavitated lung nodules are highly suggestive of GPA.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0033608 | Pulmonary nodule | Occasional (29-5%)"
explanation: Orphanet classifies pulmonary nodules as occasional in GPA.
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
chronic recurrent rhinosinusitis, cavitated lung nodules, palpable purpura or
acute kidney injury
explanation: >-
Cavitated lung nodules are listed as a key diagnostic feature prompting
investigation for AAV.
- name: Hemoptysis
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Hemoptysis
term:
id: HP:0002105
label: Hemoptysis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002105 | Hemoptysis | Frequent (79-30%)"
explanation: Orphanet classifies hemoptysis as frequent in GPA.
- name: Cough
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Cough
term:
id: HP:0012735
label: Cough
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0012735 | Cough | Frequent (79-30%)"
explanation: Orphanet classifies cough as frequent in GPA.
- name: Diffuse Alveolar Hemorrhage
category: Respiratory
frequency: OCCASIONAL
phenotype_term:
preferred_term: Diffuse alveolar hemorrhage
term:
id: HP:0025420
label: Diffuse alveolar hemorrhage
notes: Life-threatening complication requiring urgent treatment.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0025420 | Diffuse alveolar hemorrhage | Occasional (29-5%)"
explanation: Orphanet classifies diffuse alveolar hemorrhage as occasional in GPA.
- name: Recurrent Intrapulmonary Hemorrhage
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Recurrent intrapulmonary hemorrhage
term:
id: HP:0006535
label: Recurrent intrapulmonary hemorrhage
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0006535 | Recurrent intrapulmonary hemorrhage | Frequent (79-30%)"
explanation: Orphanet classifies recurrent intrapulmonary hemorrhage as frequent.
- name: Pulmonary Fibrosis
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Pulmonary fibrosis
term:
id: HP:0002206
label: Pulmonary fibrosis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002206 | Pulmonary fibrosis | Frequent (79-30%)"
explanation: Orphanet classifies pulmonary fibrosis as frequent in GPA.
- name: Respiratory Insufficiency
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Respiratory insufficiency
term:
id: HP:0002093
label: Respiratory insufficiency
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002093 | Respiratory insufficiency | Frequent (79-30%)"
explanation: Orphanet classifies respiratory insufficiency as frequent in GPA.
- name: Chronic Pulmonary Obstruction
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Chronic pulmonary obstruction
term:
id: HP:0006510
label: Chronic pulmonary obstruction
notes: Airway obstruction from endobronchial granulomatous disease.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0006510 | Chronic pulmonary obstruction | Frequent (79-30%)"
explanation: Orphanet classifies chronic pulmonary obstruction as frequent in GPA.
- name: Chest Pain
category: Respiratory
frequency: FREQUENT
phenotype_term:
preferred_term: Chest pain
term:
id: HP:0100749
label: Chest pain
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0100749 | Chest pain | Frequent (79-30%)"
explanation: Orphanet classifies chest pain as frequent in GPA.
# === Renal ===
- name: Glomerulonephritis
category: Renal
frequency: FREQUENT
phenotype_term:
preferred_term: Glomerulonephritis
term:
id: HP:0000099
label: Glomerulonephritis
notes: Rapidly progressive pauci-immune crescentic glomerulonephritis.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000099 | Glomerulonephritis | Frequent (79-30%)"
explanation: Orphanet classifies glomerulonephritis as frequent in GPA.
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
chronic recurrent rhinosinusitis, cavitated lung nodules, palpable purpura or
acute kidney injury
explanation: >-
Acute kidney injury (from glomerulonephritis) is listed as a key
presentation prompting AAV investigation.
- name: Hematuria
category: Renal
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Hematuria
term:
id: HP:0000790
label: Hematuria
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000790 | Hematuria | Very frequent (99-80%)"
explanation: Orphanet classifies hematuria as very frequent in GPA.
- name: Proteinuria
category: Renal
frequency: FREQUENT
phenotype_term:
preferred_term: Proteinuria
term:
id: HP:0000093
label: Proteinuria
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000093 | Proteinuria | Frequent (79-30%)"
explanation: Orphanet classifies proteinuria as frequent in GPA.
- name: Renal Insufficiency
category: Renal
frequency: OCCASIONAL
phenotype_term:
preferred_term: Renal insufficiency
term:
id: HP:0000083
label: Renal insufficiency
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000083 | Renal insufficiency | Occasional (29-5%)"
explanation: Orphanet classifies renal insufficiency as occasional in GPA.
# === Constitutional ===
- name: Fever
category: Constitutional
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0001945 | Fever | Very frequent (99-80%)"
explanation: Orphanet classifies fever as very frequent in GPA.
- name: Weight Loss
category: Constitutional
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Weight loss
term:
id: HP:0001824
label: Weight loss
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0001824 | Weight loss | Very frequent (99-80%)"
explanation: Orphanet classifies weight loss as very frequent in GPA.
- name: Fatigue
category: Constitutional
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0012378 | Fatigue | Very frequent (99-80%)"
explanation: Orphanet classifies fatigue as very frequent in GPA.
# === Musculoskeletal ===
- name: Arthralgia
category: Musculoskeletal
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Arthralgia
term:
id: HP:0002829
label: Arthralgia
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002829 | Arthralgia | Very frequent (99-80%)"
explanation: Orphanet classifies arthralgia as very frequent in GPA.
- name: Myalgia
category: Musculoskeletal
frequency: OCCASIONAL
phenotype_term:
preferred_term: Myalgia
term:
id: HP:0003326
label: Myalgia
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0003326 | Myalgia | Occasional (29-5%)"
explanation: Orphanet classifies myalgia as occasional in GPA.
- name: Arthritis
category: Musculoskeletal
frequency: FREQUENT
phenotype_term:
preferred_term: Arthritis
term:
id: HP:0001369
label: Arthritis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0001369 | Arthritis | Frequent (79-30%)"
explanation: Orphanet classifies arthritis as frequent in GPA.
# === Ocular ===
- name: Scleritis
category: Ophthalmologic
frequency: FREQUENT
phenotype_term:
preferred_term: Scleritis
term:
id: HP:0100532
label: Scleritis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0100532 | Scleritis | Frequent (79-30%)"
explanation: Orphanet classifies scleritis as frequent in GPA.
- name: Proptosis
category: Ophthalmologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Proptosis
term:
id: HP:0000520
label: Proptosis
notes: Due to retro-orbital granulomatous mass formation.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000520 | Proptosis | Occasional (29-5%)"
explanation: Orphanet classifies proptosis as occasional in GPA.
- name: Nasolacrimal Duct Obstruction
category: Ophthalmologic
frequency: FREQUENT
phenotype_term:
preferred_term: Nasolacrimal duct obstruction
term:
id: HP:0000579
label: Nasolacrimal duct obstruction
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000579 | Nasolacrimal duct obstruction | Frequent (79-30%)"
explanation: Orphanet classifies nasolacrimal duct obstruction as frequent in GPA.
- name: Keratitis
category: Ophthalmologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Keratitis
term:
id: HP:0000491
label: Keratitis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000491 | Keratitis | Occasional (29-5%)"
explanation: Orphanet classifies keratitis as occasional in GPA.
# === Dermatologic ===
- name: Skin Rash
category: Dermatologic
frequency: FREQUENT
phenotype_term:
preferred_term: Skin rash
term:
id: HP:0000988
label: Skin rash
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000988 | Skin rash | Frequent (79-30%)"
explanation: Orphanet classifies skin rash as frequent in GPA.
- name: Purpura
category: Dermatologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Purpura
term:
id: HP:0000979
label: Purpura
notes: Palpable purpura from leukocytoclastic vasculitis.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000979 | Purpura | Occasional (29-5%)"
explanation: Orphanet classifies purpura as occasional in GPA.
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
chronic recurrent rhinosinusitis, cavitated lung nodules, palpable purpura or
acute kidney injury
explanation: >-
Palpable purpura is listed as a key feature prompting AAV investigation.
- name: Skin Ulcer
category: Dermatologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Skin ulcer
term:
id: HP:0200042
label: Skin ulcer
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0200042 | Skin ulcer | Occasional (29-5%)"
explanation: Orphanet classifies skin ulcers as occasional in GPA.
# === Neurologic ===
- name: Peripheral Neuropathy
category: Neurologic
frequency: FREQUENT
phenotype_term:
preferred_term: Peripheral neuropathy
term:
id: HP:0009830
label: Peripheral neuropathy
notes: Mononeuritis multiplex is the characteristic pattern.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0009830 | Peripheral neuropathy | Frequent (79-30%)"
explanation: Orphanet classifies peripheral neuropathy as frequent in GPA.
- name: Cranial Nerve Paralysis
category: Neurologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Cranial nerve paralysis
term:
id: HP:0006824
label: Cranial nerve paralysis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0006824 | Cranial nerve paralysis | Occasional (29-5%)"
explanation: Orphanet classifies cranial nerve paralysis as occasional in GPA.
- name: Headache
category: Neurologic
frequency: OCCASIONAL
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002315 | Headache | Occasional (29-5%)"
explanation: Orphanet classifies headache as occasional in GPA.
# === Cardiovascular ===
- name: Pericarditis
category: Cardiovascular
frequency: OCCASIONAL
phenotype_term:
preferred_term: Pericarditis
term:
id: HP:0001701
label: Pericarditis
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0001701 | Pericarditis | Occasional (29-5%)"
explanation: Orphanet classifies pericarditis as occasional in GPA.
- name: Abnormality of the Hypothalamus-Pituitary Axis
category: Endocrine
frequency: FREQUENT
phenotype_term:
preferred_term: Abnormality of the hypothalamus-pituitary axis
term:
id: HP:0000864
label: Abnormality of the hypothalamus-pituitary axis
notes: Pituitary and hypothalamic granulomas are a documented manifestation of GPA.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000864 | Abnormality of the hypothalamus-pituitary axis | Frequent (79-30%)"
explanation: Orphanet classifies hypothalamus-pituitary axis abnormalities as frequent in GPA.
- name: Hypertension
category: Cardiovascular
frequency: OCCASIONAL
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0000822 | Hypertension | Occasional (29-5%)"
explanation: Orphanet classifies hypertension as occasional in GPA.
# === Gastrointestinal ===
- name: Abdominal Pain
category: Gastrointestinal
frequency: FREQUENT
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002027 | Abdominal pain | Frequent (79-30%)"
explanation: Orphanet classifies abdominal pain as frequent in GPA.
- name: Nausea and Vomiting
category: Gastrointestinal
frequency: FREQUENT
phenotype_term:
preferred_term: Nausea and vomiting
term:
id: HP:0002017
label: Nausea and vomiting
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0002017 | Nausea and vomiting | Frequent (79-30%)"
explanation: Orphanet classifies nausea and vomiting as frequent in GPA.
# === Laboratory / Serologic ===
- name: Anti-PR3 Antibody Positivity
category: Laboratory
frequency: FREQUENT
phenotype_term:
preferred_term: Anti-proteinase 3 antibody positivity
term:
id: HP:0033557
label: Anti-proteinase 3 antibody positivity
notes: Present in 80-90% of patients with active generalized disease.
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0033557 | Anti-proteinase 3 antibody positivity | Frequent (79-30%)"
explanation: Orphanet classifies anti-PR3 antibody positivity as frequent in GPA.
- reference: PMID:28881446
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thirty-four patients (61%) had myeloperoxidase (MPO)-ANCAs, and 17 (30%) were
positive for proteinase 3 (PR3)-ANCAs; 5 (9%) were ANCA-negative.
explanation: >-
Olmsted County cohort shows 30% PR3-ANCA positivity among all AAV patients,
though GPA specifically has higher rates.
- name: c-ANCA Positivity
category: Laboratory
frequency: FREQUENT
phenotype_term:
preferred_term: Cytoplasmic ANCA positivity
term:
id: HP:0032230
label: Cytoplasmic antineutrophil antibody positivity
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0032230 | Cytoplasmic antineutrophil antibody positivity | Frequent (79-30%)"
explanation: Orphanet classifies c-ANCA positivity as frequent in GPA.
- name: Elevated ESR
category: Laboratory
frequency: FREQUENT
phenotype_term:
preferred_term: Elevated erythrocyte sedimentation rate
term:
id: HP:0003565
label: Elevated erythrocyte sedimentation rate
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0003565 | Elevated erythrocyte sedimentation rate | Frequent (79-30%)"
explanation: Orphanet classifies elevated ESR as frequent in GPA.
- name: Anti-Neutrophil Elastase Antibody Positivity
category: Laboratory
frequency: FREQUENT
phenotype_term:
preferred_term: Anti-neutrophil elastase antibody positivity
term:
id: HP:0034104
label: Anti-neutrophil elastase antibody positivity
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0034104 | Anti-neutrophil elastase antibody positivity | Frequent (79-30%)"
explanation: Orphanet classifies anti-neutrophil elastase antibody positivity as frequent in GPA.
- name: Elevated CRP
category: Laboratory
frequency: FREQUENT
phenotype_term:
preferred_term: Elevated CRP
term:
id: HP:0011227
label: Elevated circulating C-reactive protein concentration
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0011227 | Elevated circulating C-reactive protein concentration | Frequent (79-30%)"
explanation: Orphanet classifies elevated CRP as frequent in GPA.
- name: "Vasculitis"
category: Cardiovascular
frequency: VERY_FREQUENT
description: "Vasculitis is reported as a very frequent (80-99%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Vasculitis"
term:
id: HP:0002633
label: "Vasculitis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002633 | Vasculitis | Very frequent (99-80%)"
explanation: "Orphanet records vasculitis as a very frequent (80-99%) phenotype of granulomatosis with polyangiitis."
- name: "Cerebral ischemia"
category: Neurologic
frequency: OCCASIONAL
description: >-
Cerebral ischemia is a rare central-nervous-system manifestation of
granulomatosis with polyangiitis. The Orphanet product4 dataset assigns a
"very frequent" band, but CNS involvement of any kind affects only a small
minority of patients, and cerebral ischemia is a subset of that. The primary
OCCASIONAL band reflects the clinical literature; the Orphanet band is
retained below as a source-specific context.
phenotype_term:
preferred_term: "Cerebral ischemia"
term:
id: HP:0002637
label: "Cerebral ischemia"
evidence:
- reference: PMID:11493161
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "in 9 cases the central nervous system was involved"
explanation: >-
In a prospective cohort of 128 patients with generalized granulomatosis
with polyangiitis, central nervous system involvement occurred in only 9
cases (~7%); cerebral ischemia is a subset of CNS disease, so it is far
below the Orphanet "very frequent (80-99%)" band, supporting an OCCASIONAL
primary frequency.
phenotype_contexts:
- frequency: VERY_FREQUENT
notes: >-
Source-specific assertion from the Orphanet product4 dataset, which
assigns a higher frequency band than clinical cohorts. Retained for
provenance; the primary frequency above reflects clinical-literature
estimates.
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002637 | Cerebral ischemia | Very frequent (99-80%)"
explanation: "Orphanet records cerebral ischemia as a very frequent (80-99%) phenotype of granulomatosis with polyangiitis."
- name: "Granulomatosis"
category: Systemic
frequency: VERY_FREQUENT
description: "Granulomatosis is reported as a very frequent (80-99%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Granulomatosis"
term:
id: HP:0002955
label: "Granulomatosis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002955 | Granulomatosis | Very frequent (99-80%)"
explanation: "Orphanet records granulomatosis as a very frequent (80-99%) phenotype of granulomatosis with polyangiitis."
- name: "Autoimmunity"
category: Immunologic
frequency: VERY_FREQUENT
description: "Autoimmunity is reported as a very frequent (80-99%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Autoimmunity"
term:
id: HP:0002960
label: "Autoimmunity"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0002960 | Autoimmunity | Very frequent (99-80%)"
explanation: "Orphanet records autoimmunity as a very frequent (80-99%) phenotype of granulomatosis with polyangiitis."
- name: "Glomerulopathy"
category: Renal
frequency: VERY_FREQUENT
description: "Glomerulopathy is reported as a very frequent (80-99%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Glomerulopathy"
term:
id: HP:0100820
label: "Glomerulopathy"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100820 | Glomerulopathy | Very frequent (99-80%)"
explanation: "Orphanet records glomerulopathy as a very frequent (80-99%) phenotype of granulomatosis with polyangiitis."
- name: "Polyarticular arthritis"
category: Musculoskeletal
frequency: FREQUENT
description: "Polyarticular arthritis is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Polyarticular arthritis"
term:
id: HP:0005764
label: "Polyarticular arthritis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0005764 | Polyarticular arthritis | Frequent (79-30%)"
explanation: "Orphanet records polyarticular arthritis as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Increased inflammatory response"
category: Systemic
frequency: FREQUENT
description: "Increased inflammatory response is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Increased inflammatory response"
term:
id: HP:0012649
label: "Increased inflammatory response"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0012649 | Increased inflammatory response | Frequent (79-30%)"
explanation: "Orphanet records increased inflammatory response as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Anti-myeloperoxidase antibody positivity"
category: Immunologic
frequency: FREQUENT
description: "Anti-myeloperoxidase antibody positivity is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Anti-myeloperoxidase antibody positivity"
term:
id: HP:0033559
label: "Anti-myeloperoxidase antibody positivity"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0033559 | Anti-myeloperoxidase antibody positivity | Frequent (79-30%)"
explanation: "Orphanet records anti-myeloperoxidase antibody positivity as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Inflammatory abnormality of the eye"
category: Ophthalmologic
frequency: FREQUENT
description: "Inflammatory abnormality of the eye is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Inflammatory abnormality of the eye"
term:
id: HP:0100533
label: "Inflammatory abnormality of the eye"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100533 | Inflammatory abnormality of the eye | Frequent (79-30%)"
explanation: "Orphanet records inflammatory abnormality of the eye as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Periorbital edema"
category: Ophthalmologic
frequency: FREQUENT
description: "Periorbital edema is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Periorbital edema"
term:
id: HP:0100539
label: "Periorbital edema"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0100539 | Periorbital edema | Frequent (79-30%)"
explanation: "Orphanet records periorbital edema as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Papule"
category: Dermatologic
frequency: FREQUENT
description: "Papule is reported as a frequent (30-79%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Papule"
term:
id: HP:0200034
label: "Papule"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0200034 | Papule | Frequent (79-30%)"
explanation: "Orphanet records papule as a frequent (30-79%) phenotype of granulomatosis with polyangiitis."
- name: "Prostatitis"
category: Genitourinary
frequency: OCCASIONAL
description: "Prostatitis is reported as an occasional (5-29%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Prostatitis"
term:
id: HP:0000024
label: "Prostatitis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000024 | Prostatitis | Occasional (29-5%)"
explanation: "Orphanet records prostatitis as an occasional (5-29%) phenotype of granulomatosis with polyangiitis."
- name: "Ureteral stenosis"
category: Renal
frequency: OCCASIONAL
description: "Ureteral stenosis is reported as an occasional (5-29%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Ureteral stenosis"
term:
id: HP:0000071
label: "Ureteral stenosis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000071 | Ureteral stenosis | Occasional (29-5%)"
explanation: "Orphanet records ureteral stenosis as an occasional (5-29%) phenotype of granulomatosis with polyangiitis."
- name: "Hydronephrosis"
category: Renal
frequency: OCCASIONAL
description: "Hydronephrosis is reported as an occasional (5-29%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Hydronephrosis"
term:
id: HP:0000126
label: "Hydronephrosis"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000126 | Hydronephrosis | Occasional (29-5%)"
explanation: "Orphanet records hydronephrosis as an occasional (5-29%) phenotype of granulomatosis with polyangiitis."
- name: "Chronic otitis media"
category: Otologic
frequency: OCCASIONAL
description: "Chronic otitis media is reported as an occasional (5-29%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Chronic otitis media"
term:
id: HP:0000389
label: "Chronic otitis media"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000389 | Chronic otitis media | Occasional (29-5%)"
explanation: "Orphanet records chronic otitis media as an occasional (5-29%) phenotype of granulomatosis with polyangiitis."
- name: "Retinopathy"
category: Ophthalmologic
frequency: OCCASIONAL
description: "Retinopathy is reported as an occasional (5-29%) manifestation of granulomatosis with polyangiitis in the Orphanet clinical phenotype dataset."
phenotype_term:
preferred_term: "Retinopathy"
term:
id: HP:0000488
label: "Retinopathy"
evidence:
- reference: ORPHA:900
supports: SUPPORT
evidence_source: OTHER
snippet: "HP:0000488 | Retinopathy | Occasional (29-5%)"
explanation: "Orphanet records retinopathy as an occasional (5-29%) phenotype of granulomatosis with polyangiitis."
biochemical:
- name: PR3-ANCA (c-ANCA)
presence: Elevated
context: Present in 80-90% of active generalized disease
evidence:
- reference: PMID:35479831
reference_title: ANCA Associated Vasculitis Subtypes.
supports: SUPPORT
snippet: >-
There is also evidence for classification of patients based on ANCA subtype;
those with anti-proteinase 3 antibodies (PR3) or anti-myeloperoxidase antibodies
(MPO)
have differences in response to treatment and clinical outcomes.
explanation: >-
Confirms PR3-ANCA subtyping has clinical and prognostic significance in GPA.
- name: MPO-ANCA (p-ANCA)
presence: Variable
context: Present in 10-20% of patients
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HP:0033559 | Anti-myeloperoxidase antibody positivity | Frequent (79-30%)"
explanation: >-
Orphanet classifies anti-MPO antibody positivity as frequent in GPA,
reflecting the minority of GPA patients who are MPO-ANCA positive.
- name: ESR
presence: Elevated
context: Marker of systemic inflammation and disease activity.
- name: CRP
presence: Elevated
context: Correlates with disease activity.
genetic:
- name: HLA-DPB1
association: Risk Factor
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HLA-DPB1 | major histocompatibility complex, class II, DP beta 1 | hgnc:4940 | Major susceptibility factor in"
explanation: Orphanet identifies HLA-DPB1 as a major susceptibility factor in GPA.
- name: HLA-DPA1
association: Risk Factor
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "HLA-DPA1 | major histocompatibility complex, class II, DP alpha 1 | hgnc:4938 | Major susceptibility factor in"
explanation: Orphanet identifies HLA-DPA1 as a major susceptibility factor in GPA.
- name: PRTN3
association: Risk Factor
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "PRTN3 | proteinase 3 | hgnc:9495 | Major susceptibility factor in"
explanation: >-
Orphanet identifies PRTN3 as a major susceptibility factor. PRTN3
encodes proteinase 3, the target autoantigen of PR3-ANCA.
- name: CTLA4
association: Risk Factor
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "CTLA4 | cytotoxic T-lymphocyte associated protein 4 | hgnc:2505 | Major susceptibility factor in"
explanation: Orphanet identifies CTLA4 as a major susceptibility factor in GPA.
- name: PTPN22
association: Risk Factor
evidence:
- reference: ORPHA:900
supports: SUPPORT
snippet: "PTPN22 | protein tyrosine phosphatase non-receptor type 22 | hgnc:9652 | Major susceptibility factor in"
explanation: Orphanet identifies PTPN22 as a major susceptibility factor in GPA.
- name: SERPINA1
association: Risk Factor
evidence:
- reference: PMID:16859601
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Genetic investigations have identified various candidate genes,
with alpha1-antitrypsin deficiency being the most consistently reported genetic
susceptibility factor to date.
explanation: >-
Epidemiology review confirms alpha-1 antitrypsin deficiency (SERPINA1)
as the most consistently reported genetic susceptibility factor for GPA.
environmental:
- name: Silica Dust Exposure
notes: >-
Occupational exposure to crystalline silica is the most consistently
reported environmental risk factor for GPA.
evidence:
- reference: PMID:16859601
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
evidence has grown for a possible relationship
between WG and occupational exposure to crystalline silica.
explanation: >-
Epidemiology review identifies crystalline silica as a putative
environmental risk factor for GPA.
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Exposure to silica
dust, farming and chronic nasal Staphylococcus aureus carriage are associated
with increased risk of developing AAV.
explanation: >-
Clinical practice review confirms silica dust as an established risk factor.
- name: Staphylococcus aureus Nasal Carriage
notes: >-
Chronic nasal carriage of S. aureus is associated with increased risk
of developing GPA and with disease relapse.
evidence:
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Exposure to silica
dust, farming and chronic nasal Staphylococcus aureus carriage are associated
with increased risk of developing AAV.
explanation: >-
Confirms nasal S. aureus carriage as an established risk factor for AAV.
treatments:
- name: Rituximab
description: >-
Anti-CD20 monoclonal antibody; first-line for both induction and
maintenance of remission in GPA.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: rituximab
term:
id: NCIT:C1702
label: Rituximab
evidence:
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recent data favour rituximab as a preferable option for both induction and
maintenance of remission.
explanation: >-
Recent clinical review confirms rituximab as the preferred option for both
induction and maintenance therapy in AAV.
- name: Cyclophosphamide
description: >-
Alkylating immunosuppressant; alternative for severe disease induction,
particularly organ-threatening or life-threatening disease.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: cyclophosphamide
term:
id: CHEBI:4027
label: cyclophosphamide
evidence:
- reference: PMID:1739240
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
One hundred and thirty-three patients (84%) received "standard" therapy
with daily low-dose cyclophosphamide and glucocorticoids.
explanation: >-
Landmark NIH cohort demonstrates cyclophosphamide plus glucocorticoids
as the standard induction therapy for GPA.
- name: Corticosteroids
description: >-
High-dose for induction, with subsequent taper. Glucocorticoid-sparing
strategies are increasingly preferred.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: corticosteroid
term:
id: CHEBI:50858
label: corticosteroid
evidence:
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
regimens with less glucocorticoids are equally
effective and safer in inducing remission compared with conventional regimens
explanation: >-
Recent evidence supports reduced glucocorticoid regimens as equally effective
and safer than conventional high-dose protocols.
- name: Avacopan
description: >-
Oral C5a receptor inhibitor; allows glucocorticoid reduction or elimination
during induction therapy by blocking complement-mediated neutrophil priming.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: avacopan
term:
id: NCIT:C174788
label: Avacopan
evidence:
- reference: PMID:36315063
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
avacopan is an effective glucocorticoid-sparing option.
explanation: >-
Clinical review confirms avacopan as an effective glucocorticoid-sparing
treatment option in AAV.
- reference: PMID:37781373
reference_title: The involvement of NETs in ANCA-associated vasculitis.
supports: SUPPORT
snippet: >-
Mechanistically, cytokines or complement factors activate and prime neutrophils
for ANCA-binding; thus, C5a receptor blocker has garnered attention as potential
replacement for glucocorticoids in clinical settings.
explanation: >-
Confirms the mechanistic rationale for avacopan as a C5a receptor blocker
targeting complement-mediated neutrophil priming.
target_mechanisms:
- target: Complement Alternative Pathway Activation
epidemiology:
- name: Prevalence in Europe
notes: >-
European point prevalence ranges from 24 to 157 per million (2.4-15.7
per 100,000). Higher prevalence observed in northern European countries.
evidence:
- reference: ORPHA:900
reference_title: Granulomatosis with polyangiitis (Orphanet)
supports: SUPPORT
snippet: "1-9 / 100 000 | Europe | Point prevalence | PMID:16859601"
explanation: Orphanet reports European point prevalence of GPA as 1-9 per 100,000.
- reference: PMID:16859601
reference_title: "Epidemiology of Wegener's granulomatosis: Lessons from descriptive studies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Descriptive epidemiological studies carried out
primarily in European countries estimate a prevalence of WG ranging from 24 to
157 per million and annual incidence rates from 3 to 14 per million.
explanation: >-
European epidemiology review estimates GPA prevalence at 24-157 per million.
- name: Prevalence in the United States
notes: >-
US prevalence estimated at 21.8 per 100,000 in Olmsted County, Minnesota,
substantially higher than most previous estimates worldwide.
evidence:
- reference: ORPHA:900
reference_title: Granulomatosis with polyangiitis (Orphanet)
supports: SUPPORT
snippet: "1-9 / 100 000 | United States | Point prevalence | PMID:8546743"
explanation: Orphanet reports US point prevalence of GPA as 1-9 per 100,000.
- reference: PMID:28881446
reference_title: "Epidemiology of AAV in Olmsted County, Minnesota."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The age- and sex-adjusted prevalence of GPA was 21.8 (95%CI: 12.9-30.8) per
100,000 population
explanation: >-
Olmsted County study reports GPA prevalence of 21.8 per 100,000.
- name: Incidence in the United States
notes: >-
Annual incidence of GPA in the US is approximately 1.3 per 100,000 adults.
evidence:
- reference: PMID:28881446
reference_title: "Epidemiology of AAV in Olmsted County, Minnesota."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The age- and sex-adjusted annual incidence rate of GPA for the adult population
was 1.3 (95%CI: 0.8-1.8) per 100,000 population.
explanation: >-
Olmsted County population-based study reports GPA annual incidence of
1.3 per 100,000 adults.
- name: Incidence in Europe
notes: >-
Annual incidence in Europe ranges from 3 to 14 per million.
North-South declining gradient in the Northern Hemisphere. Peak incidence
in adulthood (40-65 years) with equal sex distribution. Over 95% Caucasian.
evidence:
- reference: ORPHA:900
reference_title: Granulomatosis with polyangiitis (Orphanet)
supports: SUPPORT
snippet: "1-9 / 1 000 000 | Europe | Annual incidence | PMID:16859601"
explanation: Orphanet reports European annual incidence as 1-9 per million.
- reference: PMID:16859601
reference_title: "Epidemiology of Wegener's granulomatosis: Lessons from descriptive studies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
annual incidence rates from 3 to 14 per million.
explanation: European incidence rates estimated at 3-14 per million.
classifications:
harrisons_chapter:
- classification_value: IMMUNE_RHEUMATOLOGIC
notes: >-
Orphanet natural history indicates onset across adolescent, childhood, adult,
and elderly age groups. Disease course is typically relapsing-remitting; over
50% of patients who achieve remission experience at least one relapse.
Mortality in GPA is no longer significantly increased compared to the general
population with modern treatment, though MPA and EGPA carry higher mortality.
references:
- reference: PMID:1739240
title: 'Wegener granulomatosis: an analysis of 158 patients.'
findings:
- statement: Landmark NIH cohort establishing clinical spectrum and treatment outcomes
- reference: PMID:16859601
title: "Epidemiology of Wegener's granulomatosis: Lessons from descriptive studies and analyses of genetic and environmental risk determinants."
findings:
- statement: European prevalence 24-157 per million
- statement: Alpha-1 antitrypsin deficiency is the most consistently reported genetic risk factor
- statement: Silica exposure is the strongest environmental risk factor
- reference: PMID:25805746
title: Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
findings: []
- reference: PMID:28881446
title: 'The Epidemiology of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Olmsted County, Minnesota: A Twenty-Year US Population-Based Study.'
findings:
- statement: GPA annual incidence 1.3 per 100,000 in US
- statement: GPA prevalence 21.8 per 100,000
- statement: GPA mortality not significantly increased vs general population
- reference: PMID:36315063
title: 'Diagnosing and treating ANCA-associated vasculitis: an updated review for clinical practice.'
findings:
- statement: Rituximab preferred for induction and maintenance
- statement: Avacopan effective as glucocorticoid-sparing option
- reference: PMID:39257888
title: 'Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis.'
findings:
- statement: GPA clinical characterization and diagnostic updates
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Granulomatosis with Polyangiitis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
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Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
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Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized by granulomatous inflammation of the respiratory tract and necrotizing vasculitis of small-to-medium vessels, most often associated with anti‑neutrophil cytoplasmic antibodies (ANCA) targeting proteinase‑3 (PR3). Classic organ involvement includes upper airways (ENT), lungs, and kidneys (“ELK”), although essentially any organ system can be affected. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2)
Important evidence limitation (PMIDs): The full texts retrieved in this run (Frontiers in Medicine review; ACR/EULAR criteria paper excerpts; cohort studies; ClinicalTrials.gov records; genetics reviews/GWAS excerpts) did not reliably expose PubMed IDs in the available text chunks. Therefore, PMID-level citations and direct abstract quotes cannot be provided from the tool outputs; instead, this report cites the retrieved sources by DOI/URL and the internal evidence IDs shown in parentheses.
GPA is a systemic ANCA-associated vasculitis (AAV) with necrotizing vasculitis and granulomatous inflammation, typically involving ENT tract, lungs, and kidneys. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2)
The current evidence set did not include machine-readable entries from OMIM, Orphanet, MeSH, ICD‑10/ICD‑11, or MONDO. Accordingly, the following fields cannot be populated from tool-grounded evidence in this run: * MONDO ID: not retrieved * OMIM / Orphanet / MeSH / ICD‑10/ICD‑11: not retrieved
This report is derived from aggregated disease-level resources (reviews, consensus/criteria papers, cohort studies, systematic reviews) and trial registry entries rather than EHR-derived individual case series (except where retrospective cohorts use administrative claims). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2, kramer2024remissioninductiontherapies pages 1-2, NCT07176546 chunk 1)
GPA is generally considered multifactorial, with strong immunogenetic risk and autoimmunity centered on PR3‑ANCA in many patients. The disease is strongly associated with PR3‑ANCA by serology (see Diagnostics) and with genetic loci tied to antigen presentation (HLA class II) and the PR3/alpha‑1 antitrypsin axis. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6, alberici2015geneticaspectsof pages 4-4)
Evidence from GWAS and genetic summaries supports a polygenic architecture with a prominent HLA class II signal:
Protective variants / penetrance / inheritance: No evidence in the retrieved set quantified penetrance, carrier frequency, or protective alleles specifically for GPA; the genetic evidence supports complex/polygenic susceptibility rather than Mendelian inheritance. (merkel2017identificationoffunctional pages 1-4, alberici2015geneticaspectsof pages 4-4)
No tool-retrieved sources in this run provided specific environmental (e.g., silica), lifestyle (e.g., smoking), or infectious triggers for GPA, nor explicit gene–environment interaction analyses. This remains an evidence gap for this report.
The phenotype of GPA is heterogeneous, but a recurring pattern is ENT + pulmonary + renal involvement.
ENT manifestations * ENT involvement/signs are common (reported 80–100%). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) * Examples of reported ENT symptom frequencies: nasal crusting 75%, excessive nose‑blowing 70%, nasal obstruction 65%, epistaxis 59%; saddle‑nose deformity is described and one source reports saddle nose in 25%. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5)
Pulmonary manifestations * Pulmonary involvement is frequently reported (e.g., 62–90%). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3) * Pulmonary nodules/mass lesions: 40–70%; cavitation: 20–50%. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3) * Diffuse alveolar hemorrhage (DAH): 8.8–36% in GPA. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5)
Renal manifestations * Renal involvement: 70–85% during the course of disease; renal insufficiency at presentation: 11–17%; worsening GFR reported in 24.3%. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
Ophthalmologic/orbital and oral manifestations * Ophthalmologic signs: 50–60%; orbital lesions: 5–30%. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) * A systematic review reports ocular/orbital involvement in 16–78%, and up to 27% of patients presenting initially with ophthalmic symptoms. (moin2023ocularandorbital pages 1-2) * Oral involvement: 6–13%; “strawberry” gingival hyperplasia reported in 61.5% (in a cited subgroup context). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
Neurologic manifestations * Peripheral nervous system involvement: 11–44%; CNS involvement: 3–11.7% (often hypertrophic pachymeningitis). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5)
GPA can have substantial diagnostic delay: time from first symptoms to diagnosis ranged from 1 month to >3 years, and 36% of patients had symptoms for >1 year before diagnosis in one synthesis. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2)
Quantitative QoL effect sizes were not extractable from the retrieved text chunks. However, the following instruments are explicitly used as outcome measures in contemporary GPA/AAV trials focusing on steroid‑sparing approaches: * SF‑36 and EQ‑5D‑5L were used in the 2024 ADVOCATE rituximab‑subgroup analysis of avacopan. (geetha2024efficacyandsafety pages 4-5) * SNOT‑22 and AAV‑PRO are key secondary endpoints in an avacopan trial focused on ENT disease activity in GPA (NCT07176546). (NCT07176546 chunk 1)
Based on phenotypes explicitly described in the evidence set: * ENT: nasal crusting; epistaxis; chronic sinusitis; nasal septum perforation; saddle nose deformity. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) * Pulmonary: pulmonary nodules; cavitary lung lesions; diffuse alveolar hemorrhage; hemoptysis. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) * Renal: rapidly progressive glomerulonephritis; hematuria; proteinuria; decreased glomerular filtration rate. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6, draibe2024diagnosisandtreatment pages 2-3) * Ocular: scleritis; episcleritis; uveitis; proptosis; orbital mass. (moin2023ocularandorbital pages 1-2, draibe2024diagnosisandtreatment pages 2-3) * Neurologic: mononeuritis multiplex; cranial neuropathy; hypertrophic pachymeningitis/headache. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5)
GPA is not established as a monogenic disorder in the retrieved evidence; instead, susceptibility loci (HLA-DP, SERPINA1, PRTN3, SEMA6A, PTPN22) are repeatedly supported by GWAS and genetic syntheses. (merkel2017identificationoffunctional pages 1-4, alberici2015geneticaspectsof pages 4-4, xie2013associationofgranulomatosis pages 1-2)
PR3‑ANCA is the dominant serotype in GPA, with MPO‑ANCA more characteristic of MPA (and certain pulmonary phenotypes such as ILD). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
While the retrieved sources did not provide omics-level pathway enumerations, the disease and therapies point to: * GO BP (suggestions): neutrophil activation; complement activation; adaptive immune response; antigen processing and presentation; inflammatory response; vasculature development/vasculitis-related processes. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6, geetha2024efficacyandsafety pages 1-2) * CL (suggestions): neutrophil; macrophage; T cell; B cell; endothelial cell. (merkel2017identificationoffunctional pages 1-4)
No GPA-specific epigenomic/transcriptomic/proteomic/metabolomic results were retrieved in this run; this is an evidence gap.
No GPA-specific environmental, lifestyle, pollutant, occupational, or infectious triggers were retrieved from the current evidence set.
ANCA specificity is clinically informative. Antigen-specific PR3/MPO assays are recommended over indirect immunofluorescence in the reviewed diagnostic updates. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
Avacopan (TAVNEOS), a C5a receptor antagonist, is being deployed to reduce glucocorticoid exposure while maintaining disease control in AAV. ADVOCATE subgroup analyses demonstrate sustained remission and reduced steroid toxicity signals (see Treatment). (geetha2024efficacyandsafety pages 1-2, geetha2024efficacyandsafety pages 4-5)
The retrieved evidence supports immune and vascular pathology but did not supply histologic microanatomy beyond “granuloma/giant cells on biopsy” and “pauci‑immune glomerulonephritis.” (pyo2023comparisonofthe pages 2-4)
The evidence set indicates substantial variation and frequent delay in diagnosis, with reported symptom-to-diagnosis intervals from 1 month to >3 years and 36% of patients symptomatic for >1 year pre-diagnosis. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2)
GPA is framed as chronic with relapsing-remitting features requiring close follow-up. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2)
The available evidence supports complex polygenic risk rather than Mendelian inheritance. (merkel2017identificationoffunctional pages 1-4, alberici2015geneticaspectsof pages 4-4)
A key practical constraint is that validated diagnostic criteria for GPA are not established; diagnosis is based on a synthesis of clinical features plus supportive laboratory testing (ANCA), imaging, and histology, acknowledging that biopsy may be infeasible and/or non‑specific. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
From the 2024 diagnostic update: * PR3‑ANCA sensitivity for GPA: 74% (MPO‑ANCA sensitivity for GPA: 11%). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) * Specificity (PR3/MPO antigen-specific assays): mean 97% (range 93–99%). (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) * ANCA‑seronegative proportion reported as ~8.5%. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6)
The 2022 ACR/EULAR GPA criteria are a points-based classification tool intended for research classification, not as a stand‑alone diagnostic algorithm, and require appropriate entry criteria and exclusion of mimics. (https://doi.org/10.1002/art.41986) (robson20222022americancollege pages 5-6)
Items and weights available from a 2023 summary of the criteria include: * nasal passage involvement (+3) * cartilaginous involvement (+2) * conductive/sensorineural hearing loss (+1) * PR3‑ANCA/c‑ANCA positivity (+5) * MPO‑ANCA/p‑ANCA positivity (−1) * eosinophils ≥1000/µL (−4) * granuloma/granulomatous inflammation/giant cells on biopsy (+2) * pauci‑immune glomerulonephritis (+1) * two radiology items were retained with positive weights in the summary, but the excerpt did not include the precise radiology item wording. (pyo2023comparisonofthe pages 2-4)
Threshold: classification if cumulative score ≥5 (one summary reported “>5”). (pyo2023comparisonofthe pages 2-4, robson20222022americancollege pages 5-6)
Performance: the criteria were reported (in the retrieved summary text) to have sensitivity 93% and specificity 94% in a validation set. (robson20222022americancollege pages 5-6)
Visual evidence note: A retrieved figure crop from the criteria document shows the MPA scoring table (not the GPA table) but visually confirms the ACR/EULAR points-based approach and how PR3‑ANCA/nasal involvement are used as discriminators across AAV subtypes. (robson20222022americancollege media d7729245)
Biopsy is “strongly recommended” but is not always feasible and may show non-specific features; imaging supports detection of pulmonary nodules/masses/cavitation and sinonasal inflammation. (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3)
A 2024 multicenter European cohort (1999–2022; classified by 2022 criteria) reported: * Overall relapse rate: 34.6% (124/358). (kramer2024remissioninductiontherapies pages 4-5) * Relapse rate was higher in GPA than MPA: 41.3% vs 25.9% (p=0.006). (kramer2024remissioninductiontherapies pages 4-5) * Composite renal endpoint occurred in 25.4% and was more frequent in MPA than GPA (31.7% vs 21.2%, p=0.028). (kramer2024remissioninductiontherapies pages 4-5)
In the ADVOCATE rituximab subgroup analysis, urinary albumin-to-creatinine ratio (UACR) improved more with avacopan (LS mean ~−42%) versus prednisone taper (~+6%). (geetha2024efficacyandsafety pages 4-5)
Survival and disease-specific mortality: Not retrievable from current evidence set.
Modern GPA care generally integrates: * Immunosuppression/biologics for induction and maintenance (e.g., rituximab; cyclophosphamide in some settings) * Glucocorticoid-sparing strategies * Infection prophylaxis during intensive immunosuppression (e.g., PJP prophylaxis)
The detailed regimen algorithms (dose schedules by phenotype/severity) were not fully extractable from the retrieved guideline texts in this run; however, multiple high-quality 2024 sources document evolving steroid-sparing approaches and real-world practice trends. (geetha2024efficacyandsafety pages 4-5, kramer2024remissioninductiontherapies pages 1-2)
Efficacy/safety in RCT subgroup analysis (2024): In the rituximab induction subgroup of ADVOCATE (NCT02994927), avacopan showed: * Sustained remission at week 52: 71.0% (avacopan) vs 56.1% (prednisone taper). (geetha2024efficacyandsafety pages 5-5) * Relapse after achieving BVAS=0 by week 52: 8.7% vs 20.2%. (geetha2024efficacyandsafety pages 4-5) * Lower cumulative prednisone-equivalent exposure weeks 0–26: mean 1417 mg vs 3265 mg. (geetha2024efficacyandsafety pages 4-5) * Serious adverse events: 34.6% vs 39.3% (as reported in trial summary text). (geetha2024efficacyandsafety pages 1-2)
Real-world implementation (2024 DAH cohort): In a single-center retrospective cohort of 15 patients with AAV presenting with diffuse alveolar hemorrhage, avacopan use was associated with most patients achieving remission during a median 17-week follow-up, but there were serious infections including one death; authors highlighted practical implementation uncertainties (timing, taper strategy, access, long-term safety). (falde2024treatmentofantineutrophil pages 1-2)
Ongoing/registered trials (real-world implementation trajectory): * ENT-focused trial: NCT07176546 (not yet recruiting; estimated 2026 start) tests avacopan vs placebo added to standard care for active ENT GPA; primary endpoint is ENT remission without relapse at week 52 with no glucocorticoid exposure in the prior 4 weeks; key secondary endpoints include SNOT‑22 and AAV‑PRO and ENT surgeries/flares. (NCT07176546 chunk 1) * ARRIA phase 4: NCT06611696 (started 2024-11-15) compares avacopan + short-term reduced-dose glucocorticoid + rituximab versus a 20-week reduced-dose glucocorticoid regimen + rituximab in new-onset GPA/MPA; primary endpoint is remission at 26 weeks (BVAS=0 and <5 mg/day prednisolone) and secondary endpoints include VDI and SF‑36 through 104 weeks. (NCT06611696 chunk 1)
In the 2024 European cohort, cyclophosphamide remained frequently used, but rituximab use increased after 2013; relapse was more common in GPA than MPA. (kramer2024remissioninductiontherapies pages 1-2, kramer2024remissioninductiontherapies pages 4-5)
A 2023 US administrative claims cohort of rituximab-treated GPA (MarketScan 2011–2020) reported: * TMP‑SMX prophylaxis dispensed in 23% (426/1877); median persistence 141 days (IQR 83–248). (https://doi.org/10.1186/s13075-023-03114-7) (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2) * Prednisone ≥20 mg/day (vs none) strongly associated with prophylaxis (OR 3.96; 95% CI 3.0–5.2). (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2) * Female sex negatively associated with prophylaxis dispensing (OR 0.63; 95% CI 0.5–0.8). (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2) These data suggest incomplete real-world uptake of guideline-recommended prophylaxis and provide targets for quality improvement. (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 6-7)
Evidence in this run supports tertiary prevention via infection prophylaxis during immunosuppression (TMP‑SMX for PJP in rituximab-treated GPA), but did not yield evidence-based primary prevention strategies (e.g., vaccination schedules, exposure reduction) specific to GPA. (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2)
No evidence on naturally occurring GPA in non-human species was retrieved in this run.
No evidence on specific GPA model organisms (e.g., murine PR3-ANCA models) was retrieved in this run.
| Domain | Finding (with numbers) | Population/Context | Source (author/year/DOI) |
|---|---|---|---|
| A. Disease overview & organ involvement | GPA is a rare systemic necrotizing vasculitis with granulomatous inflammation of the respiratory tract and small-/medium-vessel vasculitis; classically affects upper airways, lungs, and kidneys | Disease overview; any organ may be affected | Potentas-Policewicz & Fijolek 2024, Front Med, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2) |
| A. Disease overview & organ involvement | ENT involvement/signs: 80–100% | GPA clinical phenotype | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) |
| A. Disease overview & organ involvement | Nasal crusting 75%; excessive nose-blowing 70%; nasal obstruction 65%; epistaxis 59%; saddle nose 25% | ENT manifestations in GPA | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) |
| A. Disease overview & organ involvement | Pulmonary involvement 62–90%; pulmonary nodules/mass lesions 40–70%; cavitation 20–50% | GPA pulmonary disease | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3) |
| A. Disease overview & organ involvement | Diffuse alveolar hemorrhage (DAH) 8.8–36% | GPA pulmonary capillaritis/DAH | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) |
| A. Disease overview & organ involvement | Kidney involvement 70–85%; renal insufficiency at presentation 11–17%; worsening GFR 24.3% | GPA renal disease course | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| A. Disease overview & organ involvement | Ocular/orbital disease 16–78%; up to 27% present initially with ophthalmic symptoms | Systematic review of ocular/orbital GPA | Moin et al. 2023, doi:10.22336/rjo.2023.38 (moin2023ocularandorbital pages 1-2) |
| A. Disease overview & organ involvement | Ophthalmologic signs 50–60%; orbital lesions 5–30% | GPA extra-renal manifestations | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| A. Disease overview & organ involvement | Oral involvement 6–13%; “strawberry” gingival hyperplasia 61.5% | GPA oral manifestations | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| A. Disease overview & organ involvement | CNS involvement 3–11.7%; PNS involvement 11–44% | GPA neurologic disease | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5) |
| B. ANCA test performance | PR3-ANCA sensitivity for GPA 74% | Diagnostic serology for GPA | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| B. ANCA test performance | MPO-ANCA sensitivity for GPA 11% | Diagnostic serology for GPA | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| B. ANCA test performance | MPO-ANCA sensitivity for MPA 73%; PR3-ANCA sensitivity for MPA 7% | Comparator data highlighting GPA/MPA serologic separation | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| B. ANCA test performance | Specificity of PR3/MPO antigen-specific assays: mean 97% (range 93–99%) | AAV serology; antigen-specific assays preferred over IIF | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| B. ANCA test performance | ANCA-negative proportion about 8.5% | GPA diagnostic workup | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6) |
| B. ANCA test performance | In ocular/orbital GPA case review: c-ANCA 59.2%, p-ANCA 10.8%, granulomas 47.7% | 306 published ocular/orbital GPA cases | Moin et al. 2023, doi:10.22336/rjo.2023.38 (moin2023ocularandorbital pages 1-2) |
| C. 2022 ACR/EULAR classification criteria | Classification threshold: cumulative score ≥5 (one summary reported >5); intended for classification, not diagnosis | Requires prior diagnosis of small-/medium-vessel vasculitis and exclusion of mimics | Robson et al. 2022, Arthritis Rheumatol, doi:10.1002/art.41986; Pyo et al. 2023, doi:10.3349/ymj.2022.0435 (pyo2023comparisonofthe pages 2-4, robson20222022americancollege pages 5-6) |
| C. 2022 ACR/EULAR classification criteria | Available weighted items: nasal passage involvement +3; cartilaginous involvement +2; hearing loss +1; PR3-ANCA/c-ANCA positivity +5; MPO-ANCA/p-ANCA positivity −1; eosinophils ≥1000/µL −4 | GPA scoring items available from review/criteria summary | Pyo et al. 2023, doi:10.3349/ymj.2022.0435 (pyo2023comparisonofthe pages 2-4) |
| C. 2022 ACR/EULAR classification criteria | Additional available weighted items: granuloma/granulomatous inflammation/giant cells on biopsy +2; pauci-immune glomerulonephritis +1; 2 radiology items retained with positive weights but details truncated in excerpt | Incomplete item extraction from available evidence | Pyo et al. 2023, doi:10.3349/ymj.2022.0435 (pyo2023comparisonofthe pages 2-4) |
| C. 2022 ACR/EULAR classification criteria | Validation cohort sizes: development set 578 GPA cases/652 comparators; validation set 146 GPA cases/161 comparators | Original derivation/validation study | Robson et al. 2022, doi:10.1002/art.41986 (from search result summary) (robson20222022americancollege pages 5-6) |
| C. 2022 ACR/EULAR classification criteria | Performance: sensitivity 93% (95% CI 87–96), specificity 94% (95% CI 89–97) | Validation set; research classification performance | Robson et al. 2022, doi:10.1002/art.41986 (from search result summary) (robson20222022americancollege pages 5-6) |
| C. 2022 ACR/EULAR classification criteria | Real-world concordance in previously diagnosed GPA: 48/65 reclassified, 73.8% concordance | Korean application study comparing 2022 criteria with prior criteria | Pyo et al. 2023, doi:10.3349/ymj.2022.0435 (pyo2023comparisonofthe pages 2-4) |
| D. Epidemiology | AAV prevalence estimated at 200–400 per million | Aggregated AAV epidemiology | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2) |
| D. Epidemiology | GPA annual incidence in European adults about 7.7–15.4 per million; Swedish study 15.4/million | Adult epidemiology | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2) |
| D. Epidemiology | Pediatric GPA incidence about 0.88–1.8 per million | Pediatric epidemiology | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2) |
| D. Epidemiology | Diagnostic delay ranged from 1 month to >3 years; 36% had symptoms >1 year before diagnosis | GPA natural history/diagnostic delay | Potentas-Policewicz & Fijolek 2024, doi:10.3389/fmed.2024.1369233 (potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3, potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2) |
| E. Treatment developments | Avacopan RTX subgroup: remission at week 26 77.6% vs 75.7%; sustained remission at week 52 71.0% vs 56.1% | ADVOCATE rituximab induction subgroup; avacopan vs prednisone taper | Geetha et al. 2024, Ann Rheum Dis, doi:10.1136/ard-2023-224816 (geetha2024efficacyandsafety pages 5-5, gattu2024superiorityofavacopan pages 5-6, geetha2024efficacyandsafety pages 1-2) |
| E. Treatment developments | Avacopan RTX subgroup relapse after BVAS=0 by week 52: 8.7% vs 20.2% | ADVOCATE rituximab subgroup | Geetha et al. 2024, doi:10.1136/ard-2023-224816 (geetha2024efficacyandsafety pages 4-5) |
| E. Treatment developments | Prednisone-equivalent cumulative exposure weeks 0–26: mean 1417 mg vs 3265 mg | Avacopan vs prednisone taper on RTX background | Geetha et al. 2024, doi:10.1136/ard-2023-224816 (geetha2024efficacyandsafety pages 4-5) |
| E. Treatment developments | UACR change favored avacopan: about −42% vs +6%; LS mean difference −45 (95% CI −60 to −24) | RTX subgroup renal response | Geetha et al. 2024, doi:10.1136/ard-2023-224816 (geetha2024efficacyandsafety pages 4-5) |
| E. Treatment developments | Serious adverse events 34.6% vs 39.3% | RTX subgroup, avacopan vs prednisone taper | Geetha et al. 2024, doi:10.1136/ard-2023-224816 (geetha2024efficacyandsafety pages 1-2) |
| E. Treatment developments | Real-world DAH cohort on avacopan: n=15, median age 66, median follow-up 17 weeks; most achieved remission, but 2 serious infections including 1 death | Single-center real-world adjunctive avacopan use in severe AAV with DAH | Falde et al. 2024, doi:10.1002/acr2.11726 (falde2024treatmentofantineutrophil pages 1-2) |
| E. Treatment developments | TMP-SMX prophylaxis in RTX-treated GPA: 426/1877 (23%) overall; new-user subgroup 281/919 (31%); median persistence 141 days (IQR 83–248); 42% continued ≥6 months | US administrative claims cohort, 2011–2020 | Mendel et al. 2023, Arthritis Res Ther, doi:10.1186/s13075-023-03114-7 (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 2-4, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 6-7) |
| E. Treatment developments | Factors associated with TMP-SMX dispensing: prednisone ≥20 mg/day OR 3.96 (95% CI 3.0–5.2); prednisone 1–19 mg/day OR 2.63 (1.8–3.8); methotrexate OR 1.48 (1.04–2.1); ICU hospitalization OR 1.95 (1.4–2.7); female sex OR 0.63 (0.5–0.8) | RTX-treated GPA; prophylaxis targeting higher-risk patients | Mendel et al. 2023, doi:10.1186/s13075-023-03114-7 (mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 2-4, mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 6-7) |
| F. Genetics | HLA-DPB1/HLA-DPA1 class II DP locus strongly associated; rs9277554 combined P=1.92×10^-50 and rs9277341 P=2.18×10^-39; signal accounted for by HLA-DPB1*04 | 2013 GWAS, 492 GPA cases/1506 controls with replication in 528 cases/1228 controls | Xie et al. 2013, Arthritis Rheum, doi:10.1002/art.38036 (xie2013associationofgranulomatosis pages 1-2) |
| F. Genetics | SEMA6A rs26595 reached genome-wide significance, P=2.09×10^-8 | GPA GWAS non-MHC locus | Xie et al. 2013, doi:10.1002/art.38036 (xie2013associationofgranulomatosis pages 1-2) |
| F. Genetics | HLA-DP rs3117242: OR 5.39, P=3.1×10^-85 in GPA; OR 7.03, P=6.2×10^-89 in PR3+ subgroup | European GWAS summary for GPA/PR3-AAV | Alberici et al. 2015, NDT, doi:10.1093/ndt/gfu386 (alberici2015geneticaspectsof pages 4-4) |
| F. Genetics | SERPINA1 rs7151526: OR 0.59, P=2.4×10^-9 in GPA+MPA; OR 0.53, P=5.6×10^-12 in PR3+ subgroup; rs28929474 OR 2.9 in PR3-ANCA+ AAV | Non-HLA susceptibility locus involving alpha-1 antitrypsin pathway | Alberici et al. 2015, doi:10.1093/ndt/gfu386; Dahlqvist et al. 2022, doi:10.1093/rheumatology/keab912 (alberici2015geneticaspectsof pages 4-4, merkel2017identificationoffunctional pages 1-4) |
| F. Genetics | PRTN3 rs62132295: OR 0.78, P=2.6×10^-5 in GPA; stronger in PR3-ANCA+ subgroup OR 0.73, P=2.6×10^-7 | PR3 autoantigen gene association | Alberici et al. 2015, doi:10.1093/ndt/gfu386 (alberici2015geneticaspectsof pages 4-4) |
| F. Genetics | Merkel 2017 replication/GWAS: HLA-DPB1 rs141530235 OR 2.99 and rs1042169 OR 2.82; PRTN3 locus linked to increased neutrophil PRTN3 expression; SERPINA1 and PTPN22 also significant | 1986 AAV cases and 4723 controls | Merkel et al. 2017, doi:10.1002/art.40034 (merkel2017identificationoffunctional pages 1-4) |
Table: This table compiles key quantitative facts on granulomatosis with polyangiitis from the gathered evidence, including organ involvement, ANCA performance, classification criteria, epidemiology, treatment outcomes, and genetic associations. It is designed as a compact reference for the main numeric findings and their sources.
References
(potentaspolicewicz2024granulomatosiswithpolyangiitis pages 1-2): Malgorzata Potentas-Policewicz and Justyna Fijolek. Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1369233, doi:10.3389/fmed.2024.1369233. This article has 49 citations.
(xie2013associationofgranulomatosis pages 1-2): Gang Xie, Delnaz Roshandel, Richard Sherva, Paul A. Monach, Emily Yue Lu, Tabitha Kung, Keisha Carrington, Steven S. Zhang, Sara L. Pulit, Stephan Ripke, Simon Carette, Paul F. Dellaripa, Jeffrey C. Edberg, Gary S. Hoffman, Nader Khalidi, Carol A. Langford, Alfred D. Mahr, E. William St.Clair, Philip Seo, Ulrich Specks, Robert F. Spiera, John H. Stone, Steven R. Ytterberg, Soumya Raychaudhuri, Paul I. W. de Bakker, Lindsay A. Farrer, Christopher I. Amos, Peter A. Merkel, and Katherine A. Siminovitch. Association of granulomatosis with polyangiitis (wegener's) with hla–dpb1*04 and sema6a gene variants: evidence from genome‐wide analysis. Arthritis & Rheumatism, 65:2457-2468, Aug 2013. URL: https://doi.org/10.1002/art.38036, doi:10.1002/art.38036. This article has 229 citations.
(mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 1-2): Arielle Mendel, Hassan Behlouli, Cristiano Soares de Moura, Évelyne Vinet, Jeffrey R. Curtis, and Sasha Bernatsky. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the united states of america: a retrospective cohort study. Arthritis Research & Therapy, Jul 2023. URL: https://doi.org/10.1186/s13075-023-03114-7, doi:10.1186/s13075-023-03114-7. This article has 5 citations and is from a domain leading peer-reviewed journal.
(kramer2024remissioninductiontherapies pages 1-2): Stefan Krämer, Kristian Vogt, Theresa Maria Schreibing, Martin Busch, Tobias Schmitt, Raoul Bergner, Sebastian Mosberger, Thomas Neumann, and Thomas Rauen. Remission induction therapies and long-term outcomes in granulomatosis with polyangiitis and microscopic polyangiitis: real-world data from a european cohort. Rheumatology International, Dec 2024. URL: https://doi.org/10.1007/s00296-024-05757-4, doi:10.1007/s00296-024-05757-4. This article has 10 citations and is from a peer-reviewed journal.
(NCT07176546 chunk 1): Robert Spiera, MD. TAVNEOS for Otolaryngologic Manifestations of Granulomatosis With Polyangiitis. Robert Spiera, MD. 2026. ClinicalTrials.gov Identifier: NCT07176546
(potentaspolicewicz2024granulomatosiswithpolyangiitis pages 5-6): Malgorzata Potentas-Policewicz and Justyna Fijolek. Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1369233, doi:10.3389/fmed.2024.1369233. This article has 49 citations.
(alberici2015geneticaspectsof pages 4-4): F. Alberici, D. Martorana, and A. Vaglio. Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 30 Suppl 1:i37-45, Dec 2015. URL: https://doi.org/10.1093/ndt/gfu386, doi:10.1093/ndt/gfu386. This article has 63 citations.
(merkel2017identificationoffunctional pages 1-4): Peter A. Merkel, Gang Xie, Paul A. Monach, Xuemei Ji, Dominic J. Ciavatta, Jinyoung Byun, Benjamin D. Pinder, Ai Zhao, Jinyi Zhang, Yohannes Tadesse, David Qian, Matthew Weirauch, Rajan Nair, Alex Tsoi, Christian Pagnoux, Simon Carette, Sharon Chung, David Cuthbertson, John C. Davis, Paul F. Dellaripa, Lindsy Forbess, Ora Gewurz‐Singer, Gary S. Hoffman, Nader Khalidi, Curry Koening, Carol A. Langford, Alfred D. Mahr, Carol McAlear, Larry Moreland, E. Philip Seo, Ulrich Specks, Robert F. Spiera, Antoine Sreih, E. William St.Clair, John H. Stone, Steven R. Ytterberg, James T. Elder, Jia Qu, Toshiki Ochi, Naoto Hirano, Jeffrey C. Edberg, Ronald J. Falk, Christopher I. Amos, and Katherine A. Siminovitch. Identification of functional and expression polymorphisms associated with risk for antineutrophil cytoplasmic autoantibody–associated vasculitis. Arthritis & Rheumatology (Hoboken, N.j.), 69:1054-1066, Apr 2017. URL: https://doi.org/10.1002/art.40034, doi:10.1002/art.40034. This article has 205 citations.
(potentaspolicewicz2024granulomatosiswithpolyangiitis pages 4-5): Malgorzata Potentas-Policewicz and Justyna Fijolek. Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1369233, doi:10.3389/fmed.2024.1369233. This article has 49 citations.
(potentaspolicewicz2024granulomatosiswithpolyangiitis pages 2-3): Malgorzata Potentas-Policewicz and Justyna Fijolek. Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1369233, doi:10.3389/fmed.2024.1369233. This article has 49 citations.
(moin2023ocularandorbital pages 1-2): Kayvon Moin, Madeleine Marta Yeakle, A. Parrill, Victoria Anne Garofalo, A. Tsiyer, Daniel Bishev, Dhir Gala, Joshua Fogel, Alexander James Hatsis, Tyler Wickas, P. Anand, and Marcelle Morcos. Ocular and orbital manifestations of granulomatosis with polyangiitis: a systematic review of published cases. Romanian Journal of Ophthalmology, 67:214-221, Oct 2023. URL: https://doi.org/10.22336/rjo.2023.38, doi:10.22336/rjo.2023.38. This article has 20 citations.
(geetha2024efficacyandsafety pages 4-5): Duvuru Geetha, Anisha Dua, Huibin Yue, Jason Springer, Carlo Salvarani, David Jayne, Peter Merkel, C. Au Peh, A. Chakera, B. Cooper, J. Kurtkoti, D. Langguth, V. Levidiotis, G. Luxton, P. Mount, D. Mudge, E. Noble, R. Phoon, A. Ritchie, J. Ryan, M. Suranyi, A. Rosenkranz, A. Kronbichler, N. Demoulin, C. Bovy, R. Hellemans, J. Hougardy, B. Sprangers, K. Wissing, C. Pagnoux, S. Barbour, S. Brachemi, S. Cournoyer, L. Girard, L. Laurin, P. Liang, D. Philibert, M. Walsh, V. Tesar, R. Becvar, P. Horak, I. Rychlik, W. Szpirt, H. Dieperink, J. Gregersen, P. Ivarsen, E. Krarup, C. Lyngsoe, C. Rigothier, J. Augusto, A. Belot, D. Chauveau, D. Cornec, N. Jourde-Chiche, M. Ficheux, A. Karras, A. Klein, F. Maurier, R. Mesbah, O. Moranne, A. Neel, T. Quemeneur, D. Saadoun, B. Terrier, P. Zaoui, M. Schaier, U. Benck, R. Bergner, M. Busch, J. Floege, F. Grundmann, H. Haller, M. Haubitz, B. Hellmich, J. Henes, B. Hohenstein, C. Hugo, C. Iking-Konert, F. Arndt, T. Kubacki, I. Kotter, P. Lamprecht, T. Lindner, J. Halbritter, H. Mehling, U. Schönermarck, N. Venhoff, V. Vielhauer, O. Witzke, I. Szombati, G. Szucs, G. Garibotto, F. Alberici, E. Brunetta, L. Dagna, S. De Vita, G. Emmi, A. Gabrielli, L. Manenti, F. Pieruzzi, D. Roccatello, C. Salvarani, M. Harigai, H. Dobashi, T. Atsumi, S. Fujimoto, N. Hagino, A. Ihata, S. Kaname, Y. Kaneko, A. Katagiri, M. Katayama, Y. Kirino, K. Kitagawa, A. Komatsuda, H. Kono, T. Kurasawa, R. Matsumura, T. Mimura, A. Morinobu, Y. Murakawa, T. Naniwa, T. Nanki, N. Ogawa, H. Oshima, K. Sada, E. Sugiyama, T. Takeuchi, H Taki, N. Tamura, T. Tsukamoto, K. Yamagata, M. Yamamura, P. van Daele, A. Rutgers, Y. Teng, R. Walker, I. Chua, M. Collins, K. Rabindranath, J. de Zoysa, M. Svensson, B. Grevbo, S. Kalstad, M. Little, M. Clarkson, E. Molloy, I. Agraz Pamplona, J. Anton, V. Barrio Lucia, S. Ciggaran, M. Cinta Cid, M. Diaz Encarnacion, X. Fulladosa Oliveras, M. Jose Soler, H. Marco Rusinol, M. Praga, L. Quintana Porras, A. Segarra, A. Bruchfeld, M. Segelmark, I. Soveri, E. Thomaidi, K. Westman, T. Neumann, M. Burnier, T. Daikeler, J. Dudler, T. Hauser, H. Seeger, B. Vogt, D. Jayne, J. Burton, R. Al Jayyousi, T. Amin, J. Andrews, L. Baines, P. Brogan, B. Dasgupta, T. Doulton, O. Flossmann, S. Griffin, J. Harper, L. Harper, D. Kidder, R. Klocke, P. Lanyon, R. Luqmani, J. McLaren, D. Makanjuola, L. McCann, A. Nandagudi, S. Selvan, E. O’Riordan, M. Patel, R. Patel, C. Pusey, R. Rajakariar, J. Robson, M. Robson, A. Salama, L. Smyth, J. Sznajd, J. Taylor, P. Merkel, A. Sreih, E. Belilos, A. Bomback, J. Carlin; Y, Chang Chen Lin, V. Derebail, S. Dragoi, A. Dua, L. Forbess, D. Geetha, P. Gipson, R. Gohh, G.T. Greenwood, S. Hugenberg, R. Jimenez, M. Kaskas, T. Kermani, A. Kivitz, C. Koening, C. Langford, G. Marder, A. Mohamed, P. Monach, N. Neyra, G. Niemer, J. Niles, R. Obi, C. Owens, D. Parks, A. Podoll, B. Rovin, R. Sam, W. Shergy, A. Silva, R. Spiera, J. Springer, C. Striebich, A. Swarup, S. Thakar, A. Tiliakos, Y. Tsai, D. Waguespack, and M. Chester Wasko. Efficacy and safety of avacopan in patients with anca-associated vasculitis receiving rituximab in a randomised trial. Annals of the Rheumatic Diseases, 83:223-232, Feb 2024. URL: https://doi.org/10.1136/ard-2023-224816, doi:10.1136/ard-2023-224816. This article has 63 citations and is from a highest quality peer-reviewed journal.
(draibe2024diagnosisandtreatment pages 2-3): Juliana Bordignon Draibe, Helena Marco, Meritxell Ibernon, Irene Agraz, Carola Arcal, Xoana Barros, Victoria Cabrera, Iara Da Silva, Montserrat Díaz, Xavier Fulladosa, Elena Guillén, Patricia Lescano, Laura Martínez Valenzuela, Eva Márquez, Nadia Martín, Ana Merino, Maru Navarro, Eva Rodríguez, Mª José Soler, Joan Torras, and Luís F. Quintana. Diagnosis and treatment of renal anca vasculitis: a summary of the consensus document of the catalan group for the study of glomerular diseases (glomcat). Journal of Clinical Medicine, 13:6793, Nov 2024. URL: https://doi.org/10.3390/jcm13226793, doi:10.3390/jcm13226793. This article has 2 citations.
(geetha2024efficacyandsafety pages 1-2): Duvuru Geetha, Anisha Dua, Huibin Yue, Jason Springer, Carlo Salvarani, David Jayne, Peter Merkel, C. Au Peh, A. Chakera, B. Cooper, J. Kurtkoti, D. Langguth, V. Levidiotis, G. Luxton, P. Mount, D. Mudge, E. Noble, R. Phoon, A. Ritchie, J. Ryan, M. Suranyi, A. Rosenkranz, A. Kronbichler, N. Demoulin, C. Bovy, R. Hellemans, J. Hougardy, B. Sprangers, K. Wissing, C. Pagnoux, S. Barbour, S. Brachemi, S. Cournoyer, L. Girard, L. Laurin, P. Liang, D. Philibert, M. Walsh, V. Tesar, R. Becvar, P. Horak, I. Rychlik, W. Szpirt, H. Dieperink, J. Gregersen, P. Ivarsen, E. Krarup, C. Lyngsoe, C. Rigothier, J. Augusto, A. Belot, D. Chauveau, D. Cornec, N. Jourde-Chiche, M. Ficheux, A. Karras, A. Klein, F. Maurier, R. Mesbah, O. Moranne, A. Neel, T. Quemeneur, D. Saadoun, B. Terrier, P. Zaoui, M. Schaier, U. Benck, R. Bergner, M. Busch, J. Floege, F. Grundmann, H. Haller, M. Haubitz, B. Hellmich, J. Henes, B. Hohenstein, C. Hugo, C. Iking-Konert, F. Arndt, T. Kubacki, I. Kotter, P. Lamprecht, T. Lindner, J. Halbritter, H. Mehling, U. Schönermarck, N. Venhoff, V. Vielhauer, O. Witzke, I. Szombati, G. Szucs, G. Garibotto, F. Alberici, E. Brunetta, L. Dagna, S. De Vita, G. Emmi, A. Gabrielli, L. Manenti, F. Pieruzzi, D. Roccatello, C. Salvarani, M. Harigai, H. Dobashi, T. Atsumi, S. Fujimoto, N. Hagino, A. Ihata, S. Kaname, Y. Kaneko, A. Katagiri, M. Katayama, Y. Kirino, K. Kitagawa, A. Komatsuda, H. Kono, T. Kurasawa, R. Matsumura, T. Mimura, A. Morinobu, Y. Murakawa, T. Naniwa, T. Nanki, N. Ogawa, H. Oshima, K. Sada, E. Sugiyama, T. Takeuchi, H Taki, N. Tamura, T. Tsukamoto, K. Yamagata, M. Yamamura, P. van Daele, A. Rutgers, Y. Teng, R. Walker, I. Chua, M. Collins, K. Rabindranath, J. de Zoysa, M. Svensson, B. Grevbo, S. Kalstad, M. Little, M. Clarkson, E. Molloy, I. Agraz Pamplona, J. Anton, V. Barrio Lucia, S. Ciggaran, M. Cinta Cid, M. Diaz Encarnacion, X. Fulladosa Oliveras, M. Jose Soler, H. Marco Rusinol, M. Praga, L. Quintana Porras, A. Segarra, A. Bruchfeld, M. Segelmark, I. Soveri, E. Thomaidi, K. Westman, T. Neumann, M. Burnier, T. Daikeler, J. Dudler, T. Hauser, H. Seeger, B. Vogt, D. Jayne, J. Burton, R. Al Jayyousi, T. Amin, J. Andrews, L. Baines, P. Brogan, B. Dasgupta, T. Doulton, O. Flossmann, S. Griffin, J. Harper, L. Harper, D. Kidder, R. Klocke, P. Lanyon, R. Luqmani, J. McLaren, D. Makanjuola, L. McCann, A. Nandagudi, S. Selvan, E. O’Riordan, M. Patel, R. Patel, C. Pusey, R. Rajakariar, J. Robson, M. Robson, A. Salama, L. Smyth, J. Sznajd, J. Taylor, P. Merkel, A. Sreih, E. Belilos, A. Bomback, J. Carlin; Y, Chang Chen Lin, V. Derebail, S. Dragoi, A. Dua, L. Forbess, D. Geetha, P. Gipson, R. Gohh, G.T. Greenwood, S. Hugenberg, R. Jimenez, M. Kaskas, T. Kermani, A. Kivitz, C. Koening, C. Langford, G. Marder, A. Mohamed, P. Monach, N. Neyra, G. Niemer, J. Niles, R. Obi, C. Owens, D. Parks, A. Podoll, B. Rovin, R. Sam, W. Shergy, A. Silva, R. Spiera, J. Springer, C. Striebich, A. Swarup, S. Thakar, A. Tiliakos, Y. Tsai, D. Waguespack, and M. Chester Wasko. Efficacy and safety of avacopan in patients with anca-associated vasculitis receiving rituximab in a randomised trial. Annals of the Rheumatic Diseases, 83:223-232, Feb 2024. URL: https://doi.org/10.1136/ard-2023-224816, doi:10.1136/ard-2023-224816. This article has 63 citations and is from a highest quality peer-reviewed journal.
(pyo2023comparisonofthe pages 2-4): Jung Yoon Pyo, Lucy Eunju Lee, Yong-Beom Park, and Sang-Won Lee. Comparison of the 2022 acr/eular classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis with previous criteria. Yonsei Medical Journal, 64:11, Jan 2023. URL: https://doi.org/10.3349/ymj.2022.0435, doi:10.3349/ymj.2022.0435. This article has 95 citations and is from a peer-reviewed journal.
(robson20222022americancollege pages 5-6): Joanna C. Robson, Peter C. Grayson, Cristina Ponte, Ravi Suppiah, Anthea Craven, Andrew Judge, Sara Khalid, Andrew Hutchings, Richard A. Watts, Peter A. Merkel, and Raashid A. Luqmani. 2022 american college of rheumatology/european alliance of associations for rheumatology classification criteria for granulomatosis with polyangiitis. Arthritis & Rheumatology, 74:393-399, Feb 2022. URL: https://doi.org/10.1002/art.41986, doi:10.1002/art.41986. This article has 797 citations and is from a highest quality peer-reviewed journal.
(robson20222022americancollege media d7729245): Joanna C. Robson, Peter C. Grayson, Cristina Ponte, Ravi Suppiah, Anthea Craven, Andrew Judge, Sara Khalid, Andrew Hutchings, Richard A. Watts, Peter A. Merkel, and Raashid A. Luqmani. 2022 american college of rheumatology/european alliance of associations for rheumatology classification criteria for granulomatosis with polyangiitis. Arthritis & Rheumatology, 74:393-399, Feb 2022. URL: https://doi.org/10.1002/art.41986, doi:10.1002/art.41986. This article has 797 citations and is from a highest quality peer-reviewed journal.
(kramer2024remissioninductiontherapies pages 4-5): Stefan Krämer, Kristian Vogt, Theresa Maria Schreibing, Martin Busch, Tobias Schmitt, Raoul Bergner, Sebastian Mosberger, Thomas Neumann, and Thomas Rauen. Remission induction therapies and long-term outcomes in granulomatosis with polyangiitis and microscopic polyangiitis: real-world data from a european cohort. Rheumatology International, Dec 2024. URL: https://doi.org/10.1007/s00296-024-05757-4, doi:10.1007/s00296-024-05757-4. This article has 10 citations and is from a peer-reviewed journal.
(geetha2024efficacyandsafety pages 5-5): Duvuru Geetha, Anisha Dua, Huibin Yue, Jason Springer, Carlo Salvarani, David Jayne, Peter Merkel, C. Au Peh, A. Chakera, B. Cooper, J. Kurtkoti, D. Langguth, V. Levidiotis, G. Luxton, P. Mount, D. Mudge, E. Noble, R. Phoon, A. Ritchie, J. Ryan, M. Suranyi, A. Rosenkranz, A. Kronbichler, N. Demoulin, C. Bovy, R. Hellemans, J. Hougardy, B. Sprangers, K. Wissing, C. Pagnoux, S. Barbour, S. Brachemi, S. Cournoyer, L. Girard, L. Laurin, P. Liang, D. Philibert, M. Walsh, V. Tesar, R. Becvar, P. Horak, I. Rychlik, W. Szpirt, H. Dieperink, J. Gregersen, P. Ivarsen, E. Krarup, C. Lyngsoe, C. Rigothier, J. Augusto, A. Belot, D. Chauveau, D. Cornec, N. Jourde-Chiche, M. Ficheux, A. Karras, A. Klein, F. Maurier, R. Mesbah, O. Moranne, A. Neel, T. Quemeneur, D. Saadoun, B. Terrier, P. Zaoui, M. Schaier, U. Benck, R. Bergner, M. Busch, J. Floege, F. Grundmann, H. Haller, M. Haubitz, B. Hellmich, J. Henes, B. Hohenstein, C. Hugo, C. Iking-Konert, F. Arndt, T. Kubacki, I. Kotter, P. Lamprecht, T. Lindner, J. Halbritter, H. Mehling, U. Schönermarck, N. Venhoff, V. Vielhauer, O. Witzke, I. Szombati, G. Szucs, G. Garibotto, F. Alberici, E. Brunetta, L. Dagna, S. De Vita, G. Emmi, A. Gabrielli, L. Manenti, F. Pieruzzi, D. Roccatello, C. Salvarani, M. Harigai, H. Dobashi, T. Atsumi, S. Fujimoto, N. Hagino, A. Ihata, S. Kaname, Y. Kaneko, A. Katagiri, M. Katayama, Y. Kirino, K. Kitagawa, A. Komatsuda, H. Kono, T. Kurasawa, R. Matsumura, T. Mimura, A. Morinobu, Y. Murakawa, T. Naniwa, T. Nanki, N. Ogawa, H. Oshima, K. Sada, E. Sugiyama, T. Takeuchi, H Taki, N. Tamura, T. Tsukamoto, K. Yamagata, M. Yamamura, P. van Daele, A. Rutgers, Y. Teng, R. Walker, I. Chua, M. Collins, K. Rabindranath, J. de Zoysa, M. Svensson, B. Grevbo, S. Kalstad, M. Little, M. Clarkson, E. Molloy, I. Agraz Pamplona, J. Anton, V. Barrio Lucia, S. Ciggaran, M. Cinta Cid, M. Diaz Encarnacion, X. Fulladosa Oliveras, M. Jose Soler, H. Marco Rusinol, M. Praga, L. Quintana Porras, A. Segarra, A. Bruchfeld, M. Segelmark, I. Soveri, E. Thomaidi, K. Westman, T. Neumann, M. Burnier, T. Daikeler, J. Dudler, T. Hauser, H. Seeger, B. Vogt, D. Jayne, J. Burton, R. Al Jayyousi, T. Amin, J. Andrews, L. Baines, P. Brogan, B. Dasgupta, T. Doulton, O. Flossmann, S. Griffin, J. Harper, L. Harper, D. Kidder, R. Klocke, P. Lanyon, R. Luqmani, J. McLaren, D. Makanjuola, L. McCann, A. Nandagudi, S. Selvan, E. O’Riordan, M. Patel, R. Patel, C. Pusey, R. Rajakariar, J. Robson, M. Robson, A. Salama, L. Smyth, J. Sznajd, J. Taylor, P. Merkel, A. Sreih, E. Belilos, A. Bomback, J. Carlin; Y, Chang Chen Lin, V. Derebail, S. Dragoi, A. Dua, L. Forbess, D. Geetha, P. Gipson, R. Gohh, G.T. Greenwood, S. Hugenberg, R. Jimenez, M. Kaskas, T. Kermani, A. Kivitz, C. Koening, C. Langford, G. Marder, A. Mohamed, P. Monach, N. Neyra, G. Niemer, J. Niles, R. Obi, C. Owens, D. Parks, A. Podoll, B. Rovin, R. Sam, W. Shergy, A. Silva, R. Spiera, J. Springer, C. Striebich, A. Swarup, S. Thakar, A. Tiliakos, Y. Tsai, D. Waguespack, and M. Chester Wasko. Efficacy and safety of avacopan in patients with anca-associated vasculitis receiving rituximab in a randomised trial. Annals of the Rheumatic Diseases, 83:223-232, Feb 2024. URL: https://doi.org/10.1136/ard-2023-224816, doi:10.1136/ard-2023-224816. This article has 63 citations and is from a highest quality peer-reviewed journal.
(falde2024treatmentofantineutrophil pages 1-2): Sam D. Falde, Amos Lal, Rodrigo Cartin‐Ceba, Lester E. Mertz, Fernando C. Fervenza, Ladan Zand, Matthew J. Koster, Kenneth J. Warrington, Augustine S. Lee, Nabeel Aslam, Andy Abril, and Ulrich Specks. Treatment of antineutrophil cytoplasmic antibody–associated vasculitis with diffuse alveolar hemorrhage with avacopan. ACR Open Rheumatology, 6:707-716, Jul 2024. URL: https://doi.org/10.1002/acr2.11726, doi:10.1002/acr2.11726. This article has 11 citations and is from a peer-reviewed journal.
(NCT06611696 chunk 1): Shunsuke Furuta. Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis. Chiba University. 2024. ClinicalTrials.gov Identifier: NCT06611696
(mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 6-7): Arielle Mendel, Hassan Behlouli, Cristiano Soares de Moura, Évelyne Vinet, Jeffrey R. Curtis, and Sasha Bernatsky. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the united states of america: a retrospective cohort study. Arthritis Research & Therapy, Jul 2023. URL: https://doi.org/10.1186/s13075-023-03114-7, doi:10.1186/s13075-023-03114-7. This article has 5 citations and is from a domain leading peer-reviewed journal.
(gattu2024superiorityofavacopan pages 5-6): Rishma Gattu, Michelle Demory Beckler, and Marc M. Kesselman. Superiority of avacopan and mepolizumab to glucocorticoid tapering in the treatment of anti-neutrophil cytoplasmic antibody (anca)-associated vasculitis: a systematic review. Cureus, Aug 2024. URL: https://doi.org/10.7759/cureus.67161, doi:10.7759/cureus.67161. This article has 5 citations.
(mendel2023trimethoprimsulfamethoxazoleprophylaxisduring pages 2-4): Arielle Mendel, Hassan Behlouli, Cristiano Soares de Moura, Évelyne Vinet, Jeffrey R. Curtis, and Sasha Bernatsky. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the united states of america: a retrospective cohort study. Arthritis Research & Therapy, Jul 2023. URL: https://doi.org/10.1186/s13075-023-03114-7, doi:10.1186/s13075-023-03114-7. This article has 5 citations and is from a domain leading peer-reviewed journal.
(potentaspolicewicz2024granulomatosiswithpolyangiitis pages 20-22): Malgorzata Potentas-Policewicz and Justyna Fijolek. Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1369233, doi:10.3389/fmed.2024.1369233. This article has 49 citations.