Diagnostic Considerations

When patients present with a limited form of granulomatosis with polyangiitis (GPA) that includes upper airway disease, orbital disease, or pulmonary disease, the differential diagnosis may include infectious and neoplastic diseases and other forms of vasculitis. Biopsies of the nasal mucosa, even when ulcerated, often are not diagnostic.

GPA localized to the upper respiratory tract should be distinguished from primary nasal natural killer/T-cell lymphoma (lethal midline granuloma) before immunosuppressive therapies are initiated, especially if an oral-nasal fistula is present and/or mass is appreciated.^[55]

GPA, which is a pulmonary-renal syndrome, should also be distinguished from other pulmonary-renal syndromes such as Goodpasture syndrome (anti–glomerular basement membrane antibody disease). Goodpasture syndrome is a much less common disorder but can manifest as renal and pulmonary findings similar to those of GPA or may overlap with GPA. Goodpasture syndrome may be recognized clinically by the absence of upper-airway abnormalities, the presence of anti–glomerular basement membrane antibodies, and the deposition of immune complexes in the basement membrane as observed on renal biopsy specimens. (See the image below).

Goodpasture syndrome: Linear deposition of immunoglobulin G and C3 are observed on a renal biopsy specimen from a patient with Goodpasture syndrome. Immunofluorescence staining. Image courtesy of K. Orr, MD.

View Media Gallery

Other conditions to consider in the differential diagnosis of GPA include the following:

Cocaine abuse
Acute glomerulonephritis
Crescentic glomerulonephritis
Diffuse proliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Membranous glomerulonephritis
Poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
Lymphomatoid granulomatosis
Malignancy
Microscopic polyangiitis
Pneumocystisjiroveci pneumonia
Bacterial pneumonia
Fungal pneumonia
Polyarteritis nodosa
Polychondritis
Nasal-type primary NK/T-cell lymphoma (formerly known as lethal midline granuloma)
Pyoderma gangrenosum
Rhinoscleroma
Sarcoidosis
Systemic lupus erythematosus

Differential Diagnoses

Workup

Garlapati P, Qurie A. Granulomatosis with Polyangiitis. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Fauci AS, Haynes BS, Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. January 1983. 98(1):76-85. [QxMD MEDLINE Link].
Manganelli P, Fietta P, Carotti M, Pesci A, Salaffi F. Respiratory system involvement in systemic vasculitis. Clin Exp Rheumatol. March-April 2006. 24:S48-S59. [QxMD MEDLINE Link].
Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15. 116(6):488-98. [QxMD MEDLINE Link].
Walsh M, et al; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13. 382 (7):622-631. [QxMD MEDLINE Link]. [Full Text].
Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. March 2009. 68:310-317. [QxMD MEDLINE Link].
[Guideline] Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken). 2021 Aug. 73 (8):1088-1105. [QxMD MEDLINE Link]. [Full Text].
Jayne D, Rasmussen N, Andrassey K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic antibodies. N Engl J Med. July 2003. 349(1):36-44. [QxMD MEDLINE Link].
Metzler C, Miehle N, Manger K, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis. Rheumatology (Oxford). July 2007. 46(7):1087-1091. [QxMD MEDLINE Link].
Falk RJ, Gross WL, Guillevin L, et al. Granulomatosis with polyangiitis (Wegener’s): an alternative name for Wegener’s granulomatosis. Ann Rheum Dis. 2011. 70:704. [QxMD MEDLINE Link].
Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. August 1990. 33(8):1101-1107. [QxMD MEDLINE Link].
Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Limited versus severe Wegener's granulomatosis: baseline patient data on patients in the Wegener's granulomatosis etanercept trial. Arthritis Rheum. August 2003. 48(8):2299-2309. [QxMD MEDLINE Link].
Finkielman JD, Lee AS, Hummel AM, et al. ANCA are detectable in nearly all patients with active severe Wegener's Granulomatosis. Am J Med. July 2007. 120:643.e9-14. [QxMD MEDLINE Link].
Boomsma MM, Stegeman CA, van der Leij MJ, et al. Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis Rheum. September 2000. 43(9):2025-33. [QxMD MEDLINE Link].
Finkielman JD, Merkel PA, Schroeder D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. November 2007. 147(9):611-9. [QxMD MEDLINE Link].
Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's Granulomatosis. N Engl J Med. 2005 Jan 27. 352(4):351-61. [QxMD MEDLINE Link].
Schlieben DJ, Korbet SM, Kimura RE, Schwartz MM, Lewis EJ. Pulmonary-renal syndrome in a newborn with placental transmission of ANCAs. Am J Kidney Dis. 2005 Apr. 45(4):758-61. [QxMD MEDLINE Link].
Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. January 1994. 120(1):12-17. [QxMD MEDLINE Link].
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15. 363(3):221-32. [QxMD MEDLINE Link].
Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. July 2010. 363(3):211-20. [QxMD MEDLINE Link].
Kallenberg CGM. Pathogenesis of PR3-ANCA associated vasculitis. J Autoimmun. February-March 2008. 30:29-36. [QxMD MEDLINE Link].
Falk RJ, Terrell RS, Charles LA, Jennett C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils todegranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA. June 1990. 87:4115-4119.
Kallenberg CGM. Pathophysiology of ANCA-associated small vessel vasculitis. Curr Rheumatol Rep. December 2010. 12(6):399-405. [QxMD MEDLINE Link].
Xiao H, Heeringa P, Liu Z, et al. The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies. Am J Pathol. July 2005. 167(1):39-45. [QxMD MEDLINE Link].
Kallenberg CGM, Heeringa P, Stegeman CA. Mechanisms of disease: pathogenesis and treatment of ANCA-associated vasculitis. Nat Clin Pract Rheumatol. December 2006. 2:661-670. [QxMD MEDLINE Link].
Moosig F, Lamprecht P, Gross WL. Wegener's Granulomatosis: the current view. Clin Rev Allergy Immunol. October 2008. 35(1-2):19-21. [QxMD MEDLINE Link].
Spagnolo P, Richeldi L, DuBois RM. Environmental triggers and susceptibility factors in idiopathic granulomatous diseases. Semin Respir Crit Care Med. December 2008. 29:610-619. [QxMD MEDLINE Link].
Carr EJ, Niederer HA, Williams J, et al. Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis. BMC Med Genet. December 2009. 10:121. [QxMD MEDLINE Link].
Jagiello P, Aries P, Arning L, et al. The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. Arthritis Rheum. December 2005. 52(12):4039-43. [QxMD MEDLINE Link].
Heckmann M, Holle JU, Arning L, et al. The Wegener's granulomatosis quantitative trait locus on chromosome 6p21.3 as characterised by tagSNP genotyping. Ann Rheum Dis. July 2008. 67(7):972-9. [QxMD MEDLINE Link].
Pendergraft WF 3rd, Preston GA, Shah RR, et al. Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3. Nat Med. January 2004. 10(1):72-9. [QxMD MEDLINE Link].
Kain R, Exner M, Brandes R, et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med. October 2008. 14(10):1088-96. [QxMD MEDLINE Link].
Hogan SL, Cooper GS, Savitz DA, et al. Association of silica exposure with anti-neutrophil cytoplasmic autoantibody small-vessel vasculitis: a population-based, case-control study. Clin J Am Soc Nephrol. March 2007. 2(2):290-9. [QxMD MEDLINE Link].
Watts RA, Lane SE, Koldingsnes W, et al. Epidemiology of vasculitis in Europe. Ann Rheum Dis. December 2001. 60(12):1156-7. [QxMD MEDLINE Link].
Lane SE, Watts R, Scott DGI. Epidemiology of systemic vasculitis. Curr Rheumatol Rep. August 2005. 7:270-275. [QxMD MEDLINE Link].
Iudici M, Quartier P, Terrier B, Mouthon L, Guillevin L, Puéchal X. Childhood-onset granulomatosis with polyangiitis and microscopic polyangiitis: systematic review and meta-analysis. Orphanet J Rare Dis. 2016 Oct 22. 11 (1):141. [QxMD MEDLINE Link]. [Full Text].
Mukhtyar C, Flossmann O, Hellmich B, et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis. July 2008. 67:1004-1010. [QxMD MEDLINE Link].
Haroun MK, Stone JH, Nair R, Racusen L, Hellmann DB, Eustace JA. Correlation of percentage of normal glomeruli with renal outcome in Wegener's granulomatosis. Am J Nephrol. September-December 2002. 22(5-6):497-503. [QxMD MEDLINE Link].
Hauer HA, Bajema IM, Van Houwelingen HC, et al. Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients. Kidney Int. November 2002. 62(5):1732-1742. [QxMD MEDLINE Link].
Renaudineau Y, Le Meur Y. Renal involvement in Wegener's Granulomatosis. Clinic Rev Allerg Immunol. October 2008. 35:22-29. [QxMD MEDLINE Link].
Walsh M, Merkel PA, Mahr A, Jayne D. Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: A meta-analysis. Arthritis Care Res (Hoboken). 2010 Aug. 62(8):1166-73. [QxMD MEDLINE Link].
Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol. September-October 2008. 26:S94-S104. [QxMD MEDLINE Link].
Seo P, Min Y-I, Holbrook JT, et al. Damage caused by Wegener's Granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum. July 2005. 52:2168-2178. [QxMD MEDLINE Link].
Le Guenno G, Mahr A, Pagnoux C, Dhote R, Guillevin L. Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides. Arthritis Rheum. 2011 Feb 17. [QxMD MEDLINE Link].
Heijl C, Harper L, Flossmann O, et al. Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis. August 2011. 70(8):1415-1421. [QxMD MEDLINE Link].
Suppiah R, Judge A, Batra R, et al. A model to predict cardiovascular events in patients with newly diagnosed wegener's granulomatosis and microscopic polyangiitis. Arthritis Care Res (Hoboken). 2011 Jan 14. [QxMD MEDLINE Link].
Aviña-Zubieta JA, Mai A, Amiri N, Dehghan N, Ann Tan J, Sayre EC, et al. Risk of Myocardial Infarction and Stroke in Patients With Granulomatosis With Polyangiitis (Wegener's): A Population-Based Study. Arthritis Rheumatol. 2016 Nov. 68 (11):2752-2759. [QxMD MEDLINE Link].
Little MA, Nightingale P, Verburgh CA, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. June 2010. 69(6):1036-43. [QxMD MEDLINE Link].
Wallace ZS, Lu N, Miloslavsky E, Unizony S, Stone JH, Choi HK. Nationwide Trends in Hospitalizations and In-Hospital Mortality of Granulomatosis with Polyangiitis. Arthritis Care Res (Hoboken). 2016 Jul 7. [QxMD MEDLINE Link].
Holle JU, Gross WL. Neurological involvement in Wegener's granulomatosis. Curr Opin Rheumatol. 2011 Jan. 23(1):7-11. [QxMD MEDLINE Link].
Esposito D, Trimpou P, Giugliano D, Dehlin M, Ragnarsson O. Pituitary dysfunction in granulomatosis with polyangiitis. Pituitary. 2017 Oct. 20 (5):594-601. [QxMD MEDLINE Link]. [Full Text].
Florian A, Slavich M, Blockmans D, Dymarkowski S, Bogaert J. Cardiac involvement in granulomatosis with polyangiitis (Wegener granulomatosis). Circulation. 2011 Sep 27. 124 (13):e342-4. [QxMD MEDLINE Link].
McGeoch L, Carette S, Cuthbertson D, Hoffman GS, Khalidi N, Koening CL, et al. Cardiac Involvement in Granulomatosis with Polyangiitis. J Rheumatol. 2015 Jul. 42 (7):1209-12. [QxMD MEDLINE Link].
Hazebroek MR, Kemna MJ, Schalla S, Sanders-van Wijk S, Gerretsen SC, Dennert R, et al. Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis. Int J Cardiol. 2015 Nov 15. 199:170-9. [QxMD MEDLINE Link].
Al-Hakeem DA, Fedele S, Carlos R, Porter S. Extranodal NK/T-cell lymphoma, nasal type. Oral Oncol. January 2007. 43(1):4-14. [QxMD MEDLINE Link].
Frankel SK, Cosgrove GP, Fischer A. Update in the diagnosis and management of pulmonary vasculitis. Chest. February 2006. 129(2):452-65. [QxMD MEDLINE Link].
Bossuyt X, Cohen Tervaert JW, Arimura Y, et al. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol. 2017 Nov. 13 (11):683-692. [QxMD MEDLINE Link].
Rottem M, Fauci AS, Hallahan CW, Kerr GS, Lebovics R, Leavitt RY, et al. Wegener granulomatosis in children and adolescents: clinical presentation and outcome. J Pediatr. 1993 Jan. 122(1):26-31. [QxMD MEDLINE Link].
Polychronopoulos VS, Prakash UBS, Golbin JM, Edell ES, Specks U. Airway involvement in Wegener's Granulomatosis. Rheum Dis Clin N Am. November 2007. 33:755-775. [QxMD MEDLINE Link].
Hervier B, Durant C, Masseau A, Ponge T, Hamidou M, Mussini JM. Use of muscle biopsies for diagnosis of systemic vasculitides. J Rheumatol. 2011 Mar. 38(3):470-4. [QxMD MEDLINE Link].
Nunokawa T, Yokogawa N, Shimada K, Enatsu K, Sugii S. The use of muscle biopsy in the diagnosis of systemic vasculitis affecting small to medium-sized vessels: a prospective evaluation in Japan. Scand J Rheumatol. 2015 Oct 8. 1-5. [QxMD MEDLINE Link].
DeGroot K, Harper L, Jayne DRW, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. May 2009. 150:670-680. [QxMD MEDLINE Link].
Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum. 2010 Jan. 62(1):9-21. [QxMD MEDLINE Link].
Clowse ME, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, et al. Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care Res (Hoboken). 2011 Dec. 63(12):1777-81. [QxMD MEDLINE Link].
Langford CA. Cyclophosphamide as induction therapy for Wegener's granulomatosis and microscopic polyangiitis. Clin Exp Immunol. May 2011. 164 (Suppl 1):31-4. [QxMD MEDLINE Link].
Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1. 369(5):417-27. [QxMD MEDLINE Link].
Garcia-Valladares I, Espinoza LR. Is rituximab superior to cyclophosphamide for ANCA-associated vasculitis for induction of remission, and with a better safety profile?. Curr Rheumatol Rep. December 2010. 12(6):395-8. [QxMD MEDLINE Link].
Aries PM, Hellmich B, Voswinkel J, et al. Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations. Ann Rheum Dis. July 2006. 65(7):853-858. [QxMD MEDLINE Link].
Seo P, Specks U, Keogh KA. Efficacy of rituximab in limited Wegener's granulomatosis with refractory granulomatous manifestations. J Rheumatol. October 2008. 35(10):2017-2023. [QxMD MEDLINE Link].
Merkel PA, Niles JL, Mertz LE, Lehane PB, Pordeli P, Erblang F. Long-Term Safety of Rituximab in Granulomatosis With Polyangiitis and in Microscopic Polyangiitis. Arthritis Care Res (Hoboken). 2021 Sep. 73 (9):1372-1378. [QxMD MEDLINE Link].
Gottenberg JE, Ravaud P, Bardin T, et al. Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum. 2010 Sep. 62(9):2625-32. [QxMD MEDLINE Link].
Jones RB, Ferraro AJ, Chaudhry AN, et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Jul. 60(7):2156-68. [QxMD MEDLINE Link].
Tesfa D, Ajeganova S, Hägglund H, et al. Late-onset neutropenia following rituximab therapy in rheumatic diseases: Association with B lymphocyte depletion and infections. Arthritis Rheum. August 2011. 63(8):2209-2214. [QxMD MEDLINE Link].
McGregor JG, Hogan SL, Hu Y, Jennette CE, Falk RJ, Nachman PH. Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease. Clin J Am Soc Nephrol. 2012 Feb. 7(2):240-7. [QxMD MEDLINE Link]. [Full Text].
Klemmer PJ, Chalermskulrat W, Reif MS, Hogan SL, Henke DC, Falk RJ. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis. December 2003. 42(6):1149-1153. [QxMD MEDLINE Link].
Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. October 1991. 40(4):757-763. [QxMD MEDLINE Link].
Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. July 2007. 18(7):2180-2188. [QxMD MEDLINE Link].
Casian A, Jayne D. Plasma exchange in the treatment of Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal limited vasculitis. Curr Opin Rheumatol. 2011 Jan. 23(1):12-7. [QxMD MEDLINE Link].
DeGroot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. August 2005. 52:2461-2469. [QxMD MEDLINE Link].
Rhee EP, Laliberte KA, Niles JL. Rituximab as maintenance therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin J Am Soc Nephrol. 2010 Aug. 5(8):1394-400. [QxMD MEDLINE Link]. [Full Text].
Sanders JS, Slot MC, Stegeman CA. Maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. November 2003. 349(21):2072-2073. [QxMD MEDLINE Link].
Slot MC, Tervaert JW, Boomsma MM, Stegeman CA. Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis. Arthritis Rheum. April 2004. 51(2):269-273. [QxMD MEDLINE Link].
Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. December 2008. 359:2790-2803. [QxMD MEDLINE Link].
Puéchal X, Pagnoux C, Perrodeau É, Hamidou M, Boffa JJ, et al. Long-term outcomes of the WEGENT trial on remission-maintenance for granulomatosis with polyangiitis or microscopic polyangiitis. Arthritis Rheumatol. 2015 Oct 16. [QxMD MEDLINE Link].
Reinhold-Keller E, Fink CO, Herlyn K, Gross WL, De Groot K. High rate of renal relapse in 71 patients with Wegener's granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum. June 2002. 47(3):326-32. [QxMD MEDLINE Link].
Langford CA, Talar-Williams C, Barron KS, Sneller MC. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med. April 2003. 114(6):463-9. [QxMD MEDLINE Link].
Langford CA, Talar-Williams C, Barron KS, Sneller MC. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. December 1999. 42(12):2666-73. [QxMD MEDLINE Link].
Sneller MC, Hoffman GS, Talar-Williams C, Kerr GS, Hallahan CW, Fauci AS. An analysis of forty-two Wegener's granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum. May 1995. 38(5):608-13. [QxMD MEDLINE Link].
Guillevin L, et al; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6. 371 (19):1771-80. [QxMD MEDLINE Link]. [Full Text].
Terrier B, et al; French Vasculitis Study Group. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann Rheum Dis. 2018 Aug. 77 (8):1150-1156. [QxMD MEDLINE Link].
Charles P, et al; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018 Aug. 77 (8):1143-1149. [QxMD MEDLINE Link].
Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. 1996 Jul 4. 335(1):16-20. [QxMD MEDLINE Link].
Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody-associated vasculitis: a systematic review. JAMA. August 2007. 298:655-669. [QxMD MEDLINE Link].
Martinez V, Cohen P, Pagnoux C, et al. Intravenous immunoglobulins for relapses of systemic vasculitides associated with antineutrophil cytoplasmic autoantibodies: results of a multicenter, prospective, open-label study of twenty-two patients. Arthritis Rheum. January 2008. 58(1):308-371. [QxMD MEDLINE Link].
Silva F, Specks U, Kalra S, et al. Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement--a prospective, open-label pilot trial. Clin J Am Soc Nephrol. March 2010. 5(3):445-53. [QxMD MEDLINE Link].
Joy MS, Hogan SL, Jennette JC, Falk RJ, Nachman PH. A pilot study using mycophenolate mofetil in relapsing or resistant ANCA small vessel vasculitis. Nephrol Dial Transplant. December 2005. 20(12):2725-2732. [QxMD MEDLINE Link].
Koukoulaki M, Jayne DR. Mycophenolate mofetil in anti-neutrophil cytoplasm antibodies-associated systemic vasculitis. Nephron Clin Pract. 2006. 102(3-4):c100-7. [QxMD MEDLINE Link].
Nowack R, Göbel U, Klooker P, Hergesell O, Andrassy K, van der Woude FJ. Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol. 1999 Sep. 10(9):1965-71. [QxMD MEDLINE Link].
Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. December 2010. 304(21):2381-2388. [QxMD MEDLINE Link].
Stone JH, Uhlfelder ML, Hellmann DB, Crook S, Bedocs NM, Hoffman GS. Etanercept combined with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum. May 2001. 44(5):1149-1154. [QxMD MEDLINE Link].
Booth A, Harper L, Hammad T, Bacon P, Griffith M, Levy J, et al. Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol. 2004 Mar. 15(3):717-21. [QxMD MEDLINE Link].
Lee RW, D'Cruz DP. Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis. Drugs. 2008. 68:747-770. [QxMD MEDLINE Link].
Sangle SR, Hughes GR, D'Cruz DP. Infliximab in patients with systemic vasculitis that is difficult to treat: poor outcome and significant adverse effects. Ann Rheum Dis. April 2007. 66(4):564-565. [QxMD MEDLINE Link].
Hinze CH, Colbert RA. B-cell depletion in Wegener's Granulomatosis. Clin Rev Allergy Immunol. June 2008. 34:372-379. [QxMD MEDLINE Link].
Schmitt WH, Birck R, Heinzel PA, et al. Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients. Nephrol Dial Transplant. June 2005. 20(6):1083-1092. [QxMD MEDLINE Link].
Birck R, Warnatz K, Lorenz HM, et al. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol. February 2003. 14(2):440-7. [QxMD MEDLINE Link].
Schmitt WH, Hagen EC, Neumann I, et al. Treatment of refractory Wegener's granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int. April 2004. 65(4):1440-1448. [QxMD MEDLINE Link].
Walsh M, Chaudhry A, Jayne D. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis. September 2008. 67(9):1322-1327. [QxMD MEDLINE Link].
Reynolds J, Tam FW, Chandraker A, et al. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest. March 2000. 105(5):643-51. [QxMD MEDLINE Link].
Girard C, Charles P, Terrier B, Bussonne G, Cohen P, Pagnoux C, et al. Tracheobronchial Stenoses in Granulomatosis With Polyangiitis (Wegener's): A Report on 26 Cases. Medicine (Baltimore). 2015 Aug. 94 (32):e1088. [QxMD MEDLINE Link].
Hoffman GS, Thomas-Golbanov CK, Chan J, Akst LM, Eliachar I. Treatment of subglottic stenosis, due to Wegener's granulomatosis, with intralesional corticosteroids and dilation. J Rheumatol. May 2003. 30(5):1017-21. [QxMD MEDLINE Link].
Langford CA, Sneller MC, Hallahan CW, et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis. Arthritis Rheum. October 1996. 39(10):1754-60. [QxMD MEDLINE Link].
Martinez Del Pero M, Jayne D, Chaudhry A, Sivasothy P, Jani P. Long-term outcome of airway stenosis in granulomatosis with polyangiitis (Wegener granulomatosis): an observational study. JAMA Otolaryngol Head Neck Surg. 2014 Nov. 140 (11):1038-44. [QxMD MEDLINE Link].
Ezzat WH, Compton RA, Basa KC, Levi J. Reconstructive Techniques for the Saddle Nose Deformity in Granulomatosis With Polyangiitis: A Systematic Review. JAMA Otolaryngol Head Neck Surg. 2017 May 1. 143 (5):507-512. [QxMD MEDLINE Link].
Wallace ZS, Wallwork R, Zhang Y, Lu N, Cortazar F, Niles JL, et al. Improved survival with renal transplantation for end-stage renal disease due to granulomatosis with polyangiitis: data from the United States Renal Data System. Ann Rheum Dis. 2018 Sep. 77 (9):1333-1338. [QxMD MEDLINE Link].
Peters JE, Gupta V, Saeed IT, Offiah C, Jawad ASM. Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review. BMC Neurol. 2018 May 1. 18 (1):59. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Saddle nose deformity in a 26-year-old man with granulomatosis with polyangiitis. Image courtesy of P. Papadopoulos, MD.
Necrotic, purpuric, and blistering plaque on the wrist in a patient with granulomatosis with polyangiitis.
Several necrotic, purpuric, and blistering papules and plaques on the hands in a patient with granulomatosis with polyangiitis.
Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis). Large ulceration of the pharynx covered with a dense necrotic membrane.
Extensive thickening of the maxillary sinuses in a patient with granulomatosis with polyangiitis. The patient also had intermittent epistaxis.
Granulomatosis with polyangiitis. Bilateral nodules observed on a plain chest radiograph in a patient with hemoptysis and hematuria. Image courtesy of G. Eschun, MD.
This 42-year-old man presented with hemoptysis, weight loss, and night sweats. He was diagnosed with the limited form of granulomatosis with polyangiitis.
Bilateral cavitating nodules in a patient with granulomatosis with polyangiitis.
Granulomatosis with polyangiitis. This patient presented with massive hemoptysis. No nodules are identified on the chest radiograph, although a subsequent CT scan showed several noncavitating nodules.
Diffuse alveolar hemorrhage in a 21-year-old man with granulomatosis with polyangiitis. Image courtesy of the US Government.
Diffuse alveolar hemorrhage in a 21-year-old man with granulomatosis with polyangiitis. Image courtesy of the US Government.
Shown is a chest radiograph of an 11-year-old girl who presented with an upper respiratory tract infection, myalgias, and arthralgias for 1 month, followed by an abrupt presentation with pallor, hemoptysis, and hypertension. Her bilateral fluffy infiltrates are suggestive of a pulmonary hemorrhage. She had an antineutrophil cytoplasmic autoantibody (ANCA)–positive pauci-immune necrotizing and crescentic glomerulonephritis associated with her pulmonary hemorrhage. Supportive therapy consisted of mechanical ventilation and hemodialysis along with immunosuppressive therapy. Her anti–glomerular basement membrane antibody test result was negative. Nearly 2 years later, she had a serum creatinine of 0.7mg/dL and no residual pulmonary disease.
An 11-year-old girl presented with an upper respiratory tract infection, myalgias, and arthralgias for 1 month followed by an abrupt presentation with pallor, hemoptysis, and hypertension. She had an antineutrophil cytoplasmic autoantibody (ANCA)–positive pauci-immune necrotizing and crescentic glomerulonephritis associated with her pulmonary hemorrhage. A follow-up chest radiograph obtained several days later shows a complete resolution of her pulmonary infiltrates. This rapid resolution is more consistent with hemorrhage than with pneumonia.
A renal biopsy specimen from a 13-year-old girl with antineutrophil cytoplasmic antibody (C-ANCA)–positive pulmonary renal syndrome. Seven weeks after presenting with sinusitis, she presented with an acute abdomen, pulmonary hemorrhage, and acute renal failure (creatinine 4.9mg/dL). This biopsy specimen shows a necrotizing and crescentic glomerulonephritis (Silver stain).
Lung biopsy specimen from a patient with granulomatosis with polyangiitis showing evidence of vasculitis and inflammation (high-power view). Image courtesy of Z. Xu, MD.
Lung biopsy specimen from a patient with granulomatosis with polyangiitis showing evidence of vasculitis and inflammation (high-power view). Image courtesy of Z. Xu, MD.
Focal glomerulonephritis with crescent formation on renal biopsy specimen, characteristic of granulomatosis with polyangiitis.
C-ANCA immunofluorescence pattern. Staining for antineutrophil cytoplasmic antibody by indirect immunofluorescence shows heavy cytoplasmic staining, whereas nuclei are nonreactive. Image courtesy of K. Orr, MD.
P-ANCA immunofluorescence pattern. Perinuclear antineutrophil cytoplasmic antibody staining pattern by indirect immunofluorescence shows perinuclear staining, whereas cytoplasm is nonreactive. Image courtesy of K. Orr, MD.
Goodpasture syndrome: Linear deposition of immunoglobulin G and C3 are observed on a renal biopsy specimen from a patient with Goodpasture syndrome. Immunofluorescence staining. Image courtesy of K. Orr, MD.

of 20

Author

Christopher L Tracy, MD Associate Program Director, Rheumatology Fellowship Program, Walter Reed National Military Medical Center

Christopher L Tracy, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Patricia J Papadopoulos, MD Staff Rheumatologist, MultiCare Rheumatology Specialists

Patricia J Papadopoulos, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology

Disclosure: Own small amount of stock for: Amazon, Johnson & Johnson, Proctor & Gamble, Cigna Corp, Pfizer.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Michael R Bye, MD Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society