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Granulomatosis with polyangiitis(GPA; WG, FORMERLY)

MedGen UID:
811223
Concept ID:
C3495801
Disease or Syndrome
Synonyms: Midline granulomatosis; Wegener Granulomatosis; Wegener's granulomatosis
SNOMED CT: Granulomatosis with polyangiitis (195353004); Necrotizing respiratory granulomatosis (195353004)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0012105
OMIM®: 608710
Orphanet: ORPHA900

Definition

Granulomatosis with polyangiitis, formerly termed Wegener granulomatosis, is a systemic disease with a complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis, and the presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) in patient sera. These ANCAs are antibodies to a defined target antigen, proteinase-3 (PR3, PRTN3; 177020), which is present within primary azurophil granules of neutrophils (PMNs) and lysozymes of monocytes. On cytokine priming of PMNs, PR3 translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate PMNs. PMNs from patients with active GPA express PR3 on their surface, produce respiratory burst, and release proteolytic enzymes after activation with PR3-ANCAs. The consequence is a self-sustaining inflammatory process (Jagiello et al., 2004). [from OMIM]

Clinical features

From HPO
Asthenia
MedGen UID:
2107
Concept ID:
C0004093
Sign or Symptom
A state characterized by a feeling of weakness and loss of strength leading to a generalized weakness of the body.
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Gangrene
MedGen UID:
6546
Concept ID:
C0017086
Disease or Syndrome
A serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies (necrosis).
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Diffuse alveolar hemorrhage
MedGen UID:
1381751
Concept ID:
C4476767
Disease or Syndrome
A type of of pulmonary hemorrhage that originates from the pulmonary microcirculation, including the alveolar capillaries, arterioles, and venules. It presents with hemoptysis, anemia, diffuse lung infiltration, and acute respiratory failure. The diagnosis is confirmed by the observation of the accumulation of red blood cells, fibrin, or hemosiderin-laden macrophage in the alveolar space on pathologic biopsy. Hemosiderin, a product of hemoglobin degradation, appears at least 48-72 hours after bleeding and is helpful in distinguishing diffuse alveolar hemorrhage from surgical trauma. Mild interstitial thickening, organizing pneumonia, or diffuse alveolar damage can also be seen.
Localized pulmonary hemorrhage
MedGen UID:
1713925
Concept ID:
C5397981
Pathologic Function
Circumscribed pulmonary hemorrhage originating from a single bleeding site in the lungs. This can be due to infections, tumorigenesis, foreign bodies, or vascular abnormalities. Patient often feel the site of bleeding, contrast CT scan or angiography may localize the bleeder.
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Mononeuritis multiplex
MedGen UID:
101790
Concept ID:
C0151295
Disease or Syndrome
A type of peripheral neuropathy that happens when there is damage to two or more different nerve areas characterized by peripheral neuropathy of both the motor and sensory nerves of at least two different nerve trunks. Different nerves are affected either simultaneously or sequentially.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Pleuritis
MedGen UID:
10807
Concept ID:
C0032231
Disease or Syndrome
Inflammation of the pleura.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Tracheal stenosis
MedGen UID:
21227
Concept ID:
C0040583
Disease or Syndrome
Narrowing of the lumen of the trachea.
Pulmonary infiltrates
MedGen UID:
116009
Concept ID:
C0235896
Finding
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
Subglottic stenosis
MedGen UID:
68668
Concept ID:
C0238441
Anatomical Abnormality
Rhinorrhea
MedGen UID:
226777
Concept ID:
C1260880
Sign or Symptom
Increased discharge of mucus from the nose.
Elevated bronchoalveolar lavage fluid neutrophil proportion
MedGen UID:
1710230
Concept ID:
C5397969
Finding
Usually, Neutrophils make up less than 3% of all cells found in the broncho-alveloar lavage fluid. In children, standard value of neutrophils is higher depending on their age (children under the age of 5 show a maximum value of 10%). This elevated cell proportion is a sign for acute and chronic infections (HP:0012387, HP:0006538) and can be associated to specific diseases.
Hemosiderin-laden macrophages in bronchoalveolar fluid
MedGen UID:
1717924
Concept ID:
C5397971
Finding
Hemosiderin-laden macrophages (HLM) in bronchoalveolar lavage (BAL) fluid were originally known as adiagnostic biomarker of alveolar hemorrhage, but have also been observed in idiopathic pulmonary fibrosis (IPF) with histopathological pattern of usual interstitial pneumonia (UIP).
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Episcleritis
MedGen UID:
4994
Concept ID:
C0014583
Disease or Syndrome
Inflammation of the episclera, a thin layer of tissue covering the white part (sclera) of the eye.
Keratitis
MedGen UID:
44013
Concept ID:
C0022568
Disease or Syndrome
Inflammation of the cornea.
Sinusitis
MedGen UID:
20772
Concept ID:
C0037199
Disease or Syndrome
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Uveitis
MedGen UID:
52961
Concept ID:
C0042164
Disease or Syndrome
Inflammation of one or all portions of the uveal tract.
Chronic otitis media
MedGen UID:
75751
Concept ID:
C0271441
Disease or Syndrome
Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.
Granulomatosis
MedGen UID:
488910
Concept ID:
C0521173
Disease or Syndrome
A granulomatous inflammation leading to multiple granuloma formation, which is a specific type of inflammation. A granuloma is a focal compact collection of inflammatory cells, mononuclear cells predominating, usually as a result of the persistence of a non-degradable product and of active cell mediated hypersensitivity.
Perinuclear antineutrophil antibody positivity
MedGen UID:
1696202
Concept ID:
C5139209
Laboratory or Test Result
The presence of autoantibodies in the serum that react against proteins predominantly expressed in perinuclear region of neutrophils.
Cytoplasmic antineutrophil antibody positivity
MedGen UID:
1690999
Concept ID:
C5139210
Finding
The presence of autoantibodies in the serum that react against proteins predominantly expressed in cytoplasmic granules of neutrophils.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
Concave nasal ridge
MedGen UID:
78105
Concept ID:
C0264169
Finding
Nasal ridge curving posteriorly to an imaginary line that connects the nasal root and tip.
Nasal mucosa vasculitis
MedGen UID:
1841783
Concept ID:
C5826769
Disease or Syndrome
Inflammation of blood vessels in the mucosa of the nasal cavity.
Skin ulcer
MedGen UID:
52369
Concept ID:
C0037299
Disease or Syndrome
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
Retinal hemorrhage
MedGen UID:
11210
Concept ID:
C0035317
Pathologic Function
Hemorrhage occurring within the retina.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGranulomatosis with polyangiitis

Professional guidelines

PubMed

Kronbichler A, Bajema IM, Bruchfeld A, Mastroianni Kirsztajn G, Stone JH
Lancet 2024 Feb 17;403(10427):683-698. doi: 10.1016/S0140-6736(23)01736-1. PMID: 38368016
Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D
Ann Rheum Dis 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764. PMID: 36927642
Kermani TA, Warrington KJ, Dua AB
Rheum Dis Clin North Am 2022 Aug;48(3):705-724. Epub 2022 Jul 5 doi: 10.1016/j.rdc.2022.03.006. PMID: 35953232

Recent clinical studies

Therapy

Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, Jackson DJ, Roufosse F, Börjesson Sjö L, Fan Y, Jison M, McCrae C, Necander S, Shavit A, Walton C, Merkel PA; MANDARA Study Group
N Engl J Med 2024 Mar 7;390(10):911-921. Epub 2024 Feb 23 doi: 10.1056/NEJMoa2311155. PMID: 38393328
White J, Dubey S
Autoimmun Rev 2023 Jan;22(1):103219. Epub 2022 Oct 22 doi: 10.1016/j.autrev.2022.103219. PMID: 36283646
Geetha D, Jefferson JA
Am J Kidney Dis 2020 Jan;75(1):124-137. Epub 2019 Jul 26 doi: 10.1053/j.ajkd.2019.04.031. PMID: 31358311
Furuta S, Iwamoto T, Nakajima H
Allergol Int 2019 Oct;68(4):430-436. Epub 2019 Jun 29 doi: 10.1016/j.alit.2019.06.004. PMID: 31266709
Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, Merkel PA, Moosig F, Specks U, Cid MC, Luqmani R, Brown J, Mallett S, Philipson R, Yancey SW, Steinfeld J, Weller PF, Gleich GJ; EGPA Mepolizumab Study Team
N Engl J Med 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079. PMID: 28514601Free PMC Article

Prognosis

Banerjee P, Jain A, Kumar U, Senapati S
Rheumatol Int 2021 Dec;41(12):2069-2089. Epub 2021 Oct 11 doi: 10.1007/s00296-021-05011-1. PMID: 34635927
Ten Berge JC, Schreurs MWJ, van Daele PLA, Rothova A
Acta Ophthalmol 2018 Aug;96(5):481-485. Epub 2018 Jan 25 doi: 10.1111/aos.13652. PMID: 29369534
Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M
Int J Immunopathol Pharmacol 2016 Jun;29(2):151-9. Epub 2015 Dec 18 doi: 10.1177/0394632015617063. PMID: 26684637Free PMC Article
Comarmond C, Pagnoux C, Khellaf M, Cordier JF, Hamidou M, Viallard JF, Maurier F, Jouneau S, Bienvenu B, Puéchal X, Aumaître O, Le Guenno G, Le Quellec A, Cevallos R, Fain O, Godeau B, Seror R, Dunogué B, Mahr A, Guilpain P, Cohen P, Aouba A, Mouthon L, Guillevin L; French Vasculitis Study Group
Arthritis Rheum 2013 Jan;65(1):270-81. doi: 10.1002/art.37721. PMID: 23044708
Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Toumelin PL; French Vasculitis Study Group (FVSG)
Medicine (Baltimore) 2011 Jan;90(1):19-27. doi: 10.1097/MD.0b013e318205a4c6. PMID: 21200183

Clinical prediction guides

Wechsler ME, Hellmich B, Cid MC, Jayne D, Tian X, Baylis L, Roufosse F
J Allergy Clin Immunol 2023 Jun;151(6):1415-1428. Epub 2023 Apr 21 doi: 10.1016/j.jaci.2023.03.011. PMID: 37086239
Grayson PC, Ponte C, Suppiah R, Robson JC, Craven A, Judge A, Khalid S, Hutchings A, Luqmani RA, Watts RA, Merkel PA; DCVAS Study Group
Ann Rheum Dis 2022 Mar;81(3):309-314. Epub 2022 Feb 2 doi: 10.1136/annrheumdis-2021-221794. PMID: 35110334
Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, Khalid S, Hutchings A, Watts RA, Merkel PA, Luqmani RA; DCVAS Investigators
Ann Rheum Dis 2022 Mar;81(3):315-320. Epub 2022 Feb 2 doi: 10.1136/annrheumdis-2021-221795. PMID: 35110333
Bettiol A, Urban ML, Dagna L, Cottin V, Franceschini F, Del Giacco S, Schiavon F, Neumann T, Lopalco G, Novikov P, Baldini C, Lombardi C, Berti A, Alberici F, Folci M, Negrini S, Sinico RA, Quartuccio L, Lunardi C, Parronchi P, Moosig F, Espígol-Frigolé G, Schroeder J, Kernder AL, Monti S, Silvagni E, Crimi C, Cinetto F, Fraticelli P, Roccatello D, Vacca A, Mohammad AJ, Hellmich B, Samson M, Bargagli E, Cohen Tervaert JW, Ribi C, Fiori D, Bello F, Fagni F, Moroni L, Ramirez GA, Nasser M, Marvisi C, Toniati P, Firinu D, Padoan R, Egan A, Seeliger B, Iannone F, Salvarani C, Jayne D, Prisco D, Vaglio A, Emmi G; European EGPA Study Group
Arthritis Rheumatol 2022 Feb;74(2):295-306. Epub 2021 Dec 30 doi: 10.1002/art.41943. PMID: 34347947Free PMC Article
Comarmond C, Cacoub P
Autoimmun Rev 2014 Nov;13(11):1121-5. Epub 2014 Aug 20 doi: 10.1016/j.autrev.2014.08.017. PMID: 25149391

Recent systematic reviews

Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D
Ann Rheum Dis 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764. PMID: 36927642
Cheng CY, Baritussio A, Giordani AS, Iliceto S, Marcolongo R, Caforio ALP
Autoimmun Rev 2022 Apr;21(4):103037. Epub 2022 Jan 5 doi: 10.1016/j.autrev.2022.103037. PMID: 34995763
Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA
Arthritis Rheumatol 2021 Aug;73(8):1366-1383. Epub 2021 Jul 8 doi: 10.1002/art.41773. PMID: 34235894
Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA
Arthritis Care Res (Hoboken) 2021 Aug;73(8):1088-1105. Epub 2021 Jul 8 doi: 10.1002/acr.24634. PMID: 34235880
Torp CK, Brüner M, Keller KK, Brouwer E, Hauge EM, McGonagle D, Kragstrup TW
Autoimmun Rev 2021 Jun;20(6):102829. Epub 2021 Apr 16 doi: 10.1016/j.autrev.2021.102829. PMID: 33872767

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