Upper respiratory tract manifestations in patients with ANCA-associated vasculitides and their association with the presence and type of ANCA

Aim of the work – to compare the frequency of upper respiratory tract (URT) involvement in patients with ANCAassociated vasculitides (AAV), to reveal its main clinical and radiological patterns and to estimate their association with the serological profile (ANCA presence and type).
Material and methods. This retrospective study evaluated 369 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The enrolled patients were diagnosed with AAV according to the ACR criteria, CHCC classification (2012) and EMA algorithm. Patients with URT manifestations underwent standard ENT assessment and X-ray/CT. Serum ANCA levels were measured by ELISA.
Results. URT involvement was diagnosed in 280 (75.9%) patients with AAV. It was significantly more common among
the patients with GPA (86.4%) and EGPA (85.5%) compared with the MPA group (29.2%) (p<0.001).
URT manifestations mainly appeared as sinusitis (77.2% – GPA; 33.3% – MPA; 70.8% – EGPA) and rhinitis with crusting (87.8%, 72.2% and 16.9% respectively).
Proteinase 3 ANCA positive patients had a significantly higher incidence of bone destructive URT lesions, including sinuses wall destruction (p<0.001) and saddle nose deformity (p=0.016), compared with myeloperoxidase-ANCA-positive patients. Similar results were obtained in the GPA group separately.
Localized disease with isolated URT involvement was observed in 41.3% cases of ANCA negative GPA (p<0.001).
Conclusion. The frequency and patterns of upper respiratory tract manifestations depend both on the nosologic form of AAV and type of ANCA. Localized forms of URT involvement can be observed in patients with GPA and are closely associated with absence of ANCA, which determines the need for especially high suspicion level.

1. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides: The proposal of an international consensus conference. Arthritis Rheum. 1994;37:187-192. doi: 10.1002/art.1780370206

2. Rao JK, Allen NB, Pincus T. Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis. Ann Intern Med. 1998;129:345-352. doi: 10.7326/0003-4819-129-5-199809010-00001

3. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum. 2013;65:1-11. doi: 10.1002/art.37715

4. Abdulkader R, Lane SE, Scott DG, Watts RA. Classification of vasculitis: EMA classification using CHCC 2012 definitions. Ann Rheum Dis. 2013;72(11):1882-1888. doi: 10.1136/annrheumdis-2013-203511

5. Beketova TV. Diagnostic algorithm for antineutrophil cytoplasmic antibody-associated systemic vasculitis. Terapevticheskii arkhiv. 2018;90(5):13-21 (In Russ.). doi: 10.26442/terarkh201890513-21

6. Wojciechowska J, Krajewski W, Krajewski P, Krecicki T. Granulomatosis with polyangiitis in otolaryngologist practice: A review of current knowledge. Clin Exp Otorhinolaryngol.2016;9:8-13. doi: 10.21053/ceo.2016.9.1.8

7. Report of the Rhinosinusitis Task Force Committee Meeting. Alexandria, Virginia, August 17, 1996. Otolaryngol Head Neck Surg.1997;117(3 Pt 2):1-68.

8. Cannady SB, Batra PS, Koening C, Lorenz RR, Citardi MJ, Langford C, et al. Sinonasal Wegener granulomatosis: a single-institution experience with 120 cases. Laryngoscope. 2009;119(4):757-761. doi: 10.1002/lary.20161

9. D’Anza B, Langford CA, Sindwani R. Sinonasal imaging findings in granulomatosis with polyangiitis (Wegener granulomatosis): A systematic review. Am J Rhinol Allergy. 2017;31(1):16-21. doi: 10.2500/ajra.2017.31.4408

10. Wojciechowska J, KręCicki T. Clinical characteristics of patients with granulomatosis with polyangiitis and microscopic polyangiitis in ENT practice: A comparative analysis. Acta Otorhinolaryngol Ital. 2018;38(6):517-527. doi: 10.14639/0392-100X-1776

11. Bacciu A, Buzio C, Giordano D, Pasanisi E, Vincenti V, Mercante G, et al. Nasal polyposis in Churg – Strauss syndrome. Laryngoscope. 2008;118:325-329. doi: 10.1097/MLG.0b013e318159889d

12. Zagvozdkina ES, Novikov PI, Moiseev SV. Clinical features of eosinophilic granulomatosis with polyangiitis in ANCA-positive and ANCA-negative patients. Clinical Pharmacology and Therapy. 2017;26(1):24-30 (In Russ.).

13. Cottin V, Bel E, Bottero P, Dalhoff K, Humbert M, Lazor R, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg – Strauss). Eur Respir J. 2016;48(5):1429-1441. doi: 10.1183/13993003.00097-2016

14. Fussner LA, Hummel AM, Schroeder DR, Silva F, Cartin-Ceba R, Snyder MR, et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheum. 2016;68:1700-1710. doi: 10.1002/art.39637

15. Terrier B, Pagnoux C, Geri G, Karras A, Khouatra C, Aumaitre O, et al. Factors predictive of ANCA-associated vasculitis relapse in patients given Rituximab-maintenance therapy. Arthritis Rheum. 2014;66(Suppl 10):779.

16. Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE, et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: The role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum. 2012;64(10):3452-3462. doi: 10.1002/art.34562

17. Miloslavsky EM, Lu N, Unizony S, Choi HK, Merkel PA, Seo P, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener’s): Distinct patient subsets. Arthritis Rheum. 2016;68:2945-2952. doi: 10.1002/art.39812

18. Bulanov NM, Makarov EA, Shchegoleva EM, Zykova AS, Vinogradova ES, Novikov PI, et al. Relationship between serologic profile (ANCA type) and clinical features of renal involvement in ANCA-associated vasculitides. Terapevticheskii arkhiv 2018;90(6):15-21 (In Russ.). doi: 10.26442/terarkh201890615-21

19. Schirmer JH, Wright MN, Herrmann K, Laudien M, Nölle B, Reinhold-Keller E, et al. Myeloperoxidase–antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener’s) is a clinically distinct subset of ANCA-associated vasculitis: A retrospective analysis of 315 patients from a German vasculitis referral center. Arthritis Rheumatol. 2016;68(12):2953-2963. doi: 10.1002/art.39786

20. Damoiseaux J, Csernok E, Rasmussen N, Moosig F, van Paassen P, Baslund B, et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): A multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis. 2017;76(4):647-653. doi: 10.1136/annrheumdis-2016-209507

21. Nölle B, Specks U, Lüdemann J, Rohrbach MS, DeRemee RA, Gross WL. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989;111(1):28-40. doi: 10.7326/0003-4819-111-1-28

22. Stone JH; Wegener’s Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener’s granulomatosis: Baseline data on patients in the Wegener’s granulomatosis etanercept trial. Arthritis Rheumatol. 2003;48:2299-2309. doi: 10.1002/art.11075

23. Holle JU, Gross WL, Holl-Ulrich K, Ambrosch P, Noelle B, Both M, et al. Prospective long-term follow-up of patients with localised Wegener’s granulomatosis: Does it occur as persistent disease stage? Ann Rheum Dis. 2010;69:1934-1939. doi: 10.1136/ard.2010.130203

24. Novikov P, Smitienko I, Bulanov N, Zykova A, Moiseev S. Testing for antineutrophil cytoplasmic antibodies (ANCAs) in patients with systemic vasculitides and other diseases. Ann Rheum Dis. 2017;76(8):e23. doi: 10.1136/annrheumdis-2016-210890

25. Smirnova IG, Bulanov NM, Zykova AS, Makarov EA, Novikov PI, Moiseev SV. ANCA-positive and ANCA-negative granulomatosis with polyangiitis. Clinical Pharmacology and Therapy. 2020;29(1):36-40 (In Russ.). doi: 10.32756/0869-5490-2020-1-36-40

26. Seo P, Specks U, Keogh KA. Efficacy of rituximab in limited Wegener’s granulomatosis with refractory granulomatous manifestations. J Rheumatol. 2008;35(10):2017-2023.

27. Hogan SL, Falk RJ, Chin H, Cai J, Jennette CE, Jennette JC, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med. 2005;143(9):621-631. doi: 10.7326/0003-4819-143-9-200511010-00005

28. Srouji IA, Andrews P, Edwards C, Lund VJ. General and rhinosinusitis-related quality of life in patients with Wegener’s granulomatosis.Laryngoscope. 2006;116(9):1621-1625. doi: 10.1097/01.mlg.0000230440.83375.4b