• Clinical science

Granulomatosis with polyangiitis (Wegener granulomatosis)

Summary

Granulomatosis with polyangiitis (GPA, previously known as Wegener granulomatosis) is a systemic vasculitis that affects both small and medium-sized vessels. Patients typically initially suffer from a limited form that may consist of constitutional symptoms and localized manifestations, such as chronic sinusitis, rhinitis, otitis media, ocular conditions, and/or skin lesions. In later stages, more serious manifestations may arise, including pulmonary complications and glomerulonephritis, although the skin, eyes, and heart may also be involved. Diagnosis is based on laboratory testing (positive for PR3-ANCA/c-ANCA), imaging, and biopsy of affected organs, which demonstrate necrotizing granulomatous inflammation. GPA is treated with immunosuppressive drugs, typically consisting of glucocorticoids combined with methotrexate, cyclophosphamide, or rituximab. Relapses are common.

Epidemiology

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Idiopathic [3]

Pathophysiology

Clinical features

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

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

Diagnostics

A biopsy is necessary to confirm the diagnosis.

Differential diagnoses

Granulomatosis with polyangiitis (GPA) Microscopic polyangiitis
Clinical presentation
  • Glomerulonephritis
  • Localized necrotizing vasculitis
  • Upper/lower respiratory tract manifestations with noncaseating, necrotizing granulomas
Laboratory tests

The differential diagnoses listed here are not exhaustive.

Treatment

Prognosis

  • Without adequate treatment, the 1-year survival rate is < 20%. [16]
  • 5-year survival with adequate treatment is approx. 80%. [17]
  • 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): pp. 54–58. doi: 10.1016/j.radcr.2019.09.037.
  • 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): pp. 2067–2076. doi: 10.1002/art.40577.
  • 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): pp. 237–52. doi: 10.2215/CJN.03550807.
  • 4. Xiao H, Hu P, Falk RJ, Jennette JC. Overview of the Pathogenesis of ANCA-Associated Vasculitis. Kidney Diseases. 2015; 1(4): pp. 205–215. doi: 10.1159/000442323.
  • 5. Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011; 20(3): pp. 263–70. doi: 10.1097/MNH.0b013e3283456731.
  • 6. Nakazawa D, Masuda S, Tomaru U, Ishizu A. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nature reviews. Rheumatology. 2019; 15(2): pp. 91–101. doi: 10.1038/s41584-018-0145-y.
  • 7. Falk RJ, Jennette JC. ANCA disease: where is this field heading?. J Am Soc Nephrol. 2010; 21(5): pp. 745–52. doi: 10.1681/ASN.2009121238.
  • 8. Yuen J, Pluthero FG, Douda DN, et al. NETosing Neutrophils Activate Complement Both on Their Own NETs and Bacteria via Alternative and Non-alternative Pathways. Frontiers in immunology. 2016; 7: p. 137. doi: 10.3389/fimmu.2016.00137.
  • 9. 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): pp. S123–6. pmid: 23814553.
  • 10. 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): pp. 247–51. doi: 10.5051/jpis.2015.45.6.247.
  • 11. Qasim A, Patel J. ANCA Positive Vasculitis (ANCA Positive Angitis). StatPearls. 2020. pmid: 32119259.
  • 12. Walsh M, Merkel PA, Peh CA, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020; 382(7): pp. 622–631. doi: 10.1056/NEJMoa1803537.
  • 13. Miloslavsky EM, Niles JL, Wallace ZS, et al. Reducing glucocorticoid duration in ANCA-associated vasculitis: A pilot trial. Semin Arthritis Rheum. 2018; 48(2): pp. 288–292. doi: 10.1016/j.semarthrit.2018.01.013.
  • 14. Charles P, Perrodeau É, Samson M, et al. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med. 2020; 173(3): pp. 179–187. doi: 10.7326/M19-3827.
  • 15. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008; 359(26): pp. 2790–803. doi: 10.1056/NEJMoa0802311.
  • 16. 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): pp. 61–9. doi: 10.5582/irdr.2016.01014.
  • 17. Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2010; 70(3): pp. 488–494. doi: 10.1136/ard.2010.137778.
  • Gaillard F, et all. Granulomatosis with polyangiitis. https://radiopaedia.org/articles/granulomatosis-with-polyangiitis. Updated April 13, 2017. Accessed April 13, 2017.
last updated 10/16/2020
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