Granulomatosis with polyangiitis

Last updated: June 30, 2023

Summarytoggle arrow icon

Granulomatosis with polyangiitis (GPA; previously referred to as Wegener granulomatosis) is a systemic vasculitis that affects both small and medium-sized vessels. Patients typically initially present with a limited form that consists of constitutional symptoms and localized manifestations, such as chronic sinusitis, rhinitis, otitis media, ocular involvement, and/or skin lesions. More serious manifestations may develop in later stages, including pulmonary complications and glomerulonephritis; the heart may also be involved. Testing modalities include laboratory studies, imaging, and biopsy. Diagnosis is confirmed by biopsy findings of necrotizing granulomatous inflammation. Pharmacotherapy consists of immunosuppressive drugs, typically glucocorticoids combined with methotrexate, cyclophosphamide, or rituximab. Relapses are common.

Definitiontoggle arrow icon

Granulomatosis with polyangiitis is a type of systemic ANCA-associated vasculitis of small and medium-sized vessels characterized by necrotizing granulomatous inflammation, and it typically affects the lungs, paranasal sinuses, and kidneys. [1]

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Upper respiratory manifestations (i.e., purulent, sometimes bloody discharge, chronic nasopharyngeal infections, saddle nose deformity) are the most common chief complaints.

Classic GPA triad: necrotizing vasculitis of small arteries, upper/lower respiratory tract manifestations, and glomerulonephritis

Diagnosticstoggle arrow icon

General principles [7][8]

  • Suspect GPA in patients with either:
  • Consult rheumatology.
  • Obtain laboratory and imaging studies to:
    • Determine the extent and severity of organ involvement
    • Rule out differential diagnoses (e.g., infection, neoplasm)
  • Characteristic histopathological findings confirm the diagnosis.

Laboratory studies [7]

While positive PR3-ANCAs have a high sensitivity for GPA (∼ 98%), their absence does not exclude the diagnosis. [8]

Imaging studies [7]

Chest imaging

  • Obtain a chest X-ray or CT chest for all patients to assess for lung involvement.
  • Supportive findings
    • Multiple bilateral cavitating nodular lesions
    • Pulmonary hemorrhage

Additional studies

Consider additional studies to assess for organ involvement as needed, e.g.:

Biopsy [7][10]

  • Indications
    • Consider in all patients to confirm the diagnosis.
    • In patients with renal disease, a kidney biopsy may be required to assess for relapse and/or irreversible damage.
  • Samples: may be obtained from any affected tissue
  • Findings [10]

Biopsy may not be required in certain patients, e.g., those with characteristic clinical features and positive PR3-ANCA, because results will not affect management. [7]

For patients with severe kidney or lung disease, do not delay treatment for biopsy. Several days of treatment do not significantly reduce the biopsy yield of biopsy samples. [7]

Differential diagnosestoggle arrow icon

Granulomatosis with polyangiitis (GPA) Microscopic polyangiitis
Clinical presentation
Laboratory tests

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

General principles [1][10]

GPA can rarely cause life-threatening hemoptysis and/or ARDS from diffuse alveolar hemorrhage that may require mechanical ventilation and/or ECMO. [11]

Pharmacotherapy [1]

Induction of remission

Indication: patients with active disease

Maintenance of remission

Indication: patients who initially presented with severe disease

Assessment for concurrent immunosuppressive states (e.g., HIV, TB, diabetes mellitus) is required before starting immunosuppressive therapy. [7]

Management of associated symptoms [7]

Supportive care [1][7]

Prognosistoggle arrow icon

Referencestoggle arrow icon

  1. Pace C, Presicce M, Lamacchia F, Ferrari D, Sergiacomi G. Onset of granulomatosis with polyangiitis obscured by heart disease in an elderly man.. Radiology case reports. 2020; 15 (1): p.54-58.doi: 10.1016/j.radcr.2019.09.037 . | Open in Read by QxMD
  2. Panupattanapong S, Stwalley DL, White AJ, Olsen MA, French AR, Hartman ME. Epidemiology and Outcomes of Granulomatosis With Polyangiitis in Pediatric and Working-Age Adult Populations In the United States: Analysis of a Large National Claims Database.. Arthritis & rheumatology (Hoboken, N.J.). 2018; 70 (12): p.2067-2076.doi: 10.1002/art.40577 . | Open in Read by QxMD
  3. de Lind van Wijngaarden RA, van Rijn L, Hagen EC, et al. Hypotheses on the etiology of antineutrophil cytoplasmic autoantibody associated vasculitis: the cause is hidden, but the result is known.. Clin J Am Soc Nephrol. 2008; 3 (1): p.237-52.doi: 10.2215/CJN.03550807 . | Open in Read by QxMD
  4. Heera R, Choudhary K, Beena VT, Simon R. Strawberry gingivitis: A diagnostic feature of gingival Wegener's granulomatosis!. Dental research journal. 2012; 9 (Suppl 1): p.S123-6.
  5. Sung IY, Kim YM, Cho YC, Son JH. Role of gingival manifestation in diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis).. Journal of periodontal & implant science. 2015; 45 (6): p.247-51.doi: 10.5051/jpis.2015.45.6.247 . | Open in Read by QxMD
  6. Kitching AR, Anders HJ, Basu N, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020; 6 (1).doi: 10.1038/s41572-020-0204-y . | Open in Read by QxMD
  7. Bossuyt X, Cohen Tervaert JW, Arimura Y, et al. Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol. 2017; 13 (11): p.683-692.doi: 10.1038/nrrheum.2017.140 . | Open in Read by QxMD
  8. Almaani S, Fussner LA, Brodsky S, Meara AS, Jayne D. ANCA-Associated Vasculitis: An Update. J Clin Med. 2021; 10 (7): p.1446.doi: 10.3390/jcm10071446 . | Open in Read by QxMD
  9. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016; 75 (9): p.1583-1594.doi: 10.1136/annrheumdis-2016-209133 . | Open in Read by QxMD
  10. Chung SA, Langford CA, Maz M, et al. American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis Care Res. 2021; 73 (8): p.1088-1105.doi: 10.1002/acr.24634 . | Open in Read by QxMD
  11. Da Silva RC, Adhikari P. Granulomatosis With Polyangiitis Presenting With Diffuse Alveolar Hemorrhage: A Systematic Review. Cureus. 2022.doi: 10.7759/cureus.29909 . | Open in Read by QxMD
  12. Kubaisi B, Abu Samra K, Foster CS. Granulomatosis with polyangiitis (Wegener's disease): An updated review of ocular disease manifestations.. Intractable & rare diseases research. 2016; 5 (2): p.61-9.doi: 10.5582/irdr.2016.01014 . | Open in Read by QxMD
  13. Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2010; 70 (3): p.488-494.doi: 10.1136/ard.2010.137778 . | Open in Read by QxMD

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