Advertisement

Clinical Rheumatology

, Volume 37, Issue 4, pp 1075–1083 | Cite as

Ear, nose and throat involvement in granulomatosis with polyangiitis: how it presents and how it determines disease severity and long-term outcomes

  • Mara Felicetti
  • Diego Cazzador
  • Roberto Padoan
  • Alfonso Luca Pendolino
  • Chiara Faccioli
  • Ennio Nardello
  • Alvise Berti
  • Marina Silvestrini
  • Giuseppe Paolazzi
  • Giuliano Brunori
  • Elisabetta Zanoletti
  • Enzo Emanuelli
  • Alessandro Martini
  • Franco Schiavon
Original Article

Abstract

Ear, nose and throat (ENT) manifestations in granulomatosis with polyangiitis (GPA) represent the most frequent symptoms at disease onset. The aim of the study was to analyse ENT involvement at diagnosis, as well as how it could influence relapse rate, mortality and disease severity. A retrospective non-controlled cohort study was performed including all consecutive diagnosed GPA from 1996 to 2016 in two rheumatology centres of Northern Italy, focusing particularly on ENT presenting signs and symptoms at baseline. Eighty-nine patients (48.3% females) with new onset GPA were evaluated. They were mostly Caucasian (97.7%), middle aged (mean 54.5 years) and more frequently anti-neutrophil cytoplasmic antibodies (ANCA) positive (78.6%) with PR3 specificity (81.4%). At diagnosis, ENT involvement was reported in 71.9% patients, second only to systemic symptoms. These patients were significantly younger at disease onset (0.013), with less frequent renal involvement (0.014) irrespectively to ANCA status, but with significantly higher Vasculitis Damage Index (VDI) (0.001). The most frequent ENT manifestation was sinonasal involvement (58.4%, 73% of which with nasal inflammation/chronic sinusitis and 48% with nasal crusting), while otologic involvement (mainly otitis media/otomastoiditis) was observed in 34.8%. ENT-GPA patients presented a higher survival rate at 5 years (98.1 vs 77.7%, 0.049), and ENT involvement resulted to be an independent predictor of better outcome (OR 0.37, 95% CI 0.2–0.8, 0.019). Our data confirms that ENT involvement is not only one of the key clinical features of GPA, but also could point out a milder GPA subset with lower renal involvement and lower mortality rate, irrespectively to ANCA status.

Keywords

Granulomatosis Polyangiitis Long-term outcomes ENT involvement Damage ANCA 

Notes

Compliance with ethical standards

Disclosures

None.

References

  1. 1.
    Falk RJ, Gross WL, Guillevin L, Hoffman GS, Jayne DRW, Jennette JC, Kallenberg CGM, Luqmani R, Mahr AD, Matteson EL, Merkel PA, Specks U, Watts RA, American College of Rheumatology, American Society of Nephrology, European League Against Rheumatism (2011) Granulomatosis with polyangiitis (Wegener’s): an alternative name for Wegener’s granulomatosis. Arthritis Rheum 63(4):863–864.  https://doi.org/10.1002/art.30286 CrossRefPubMedGoogle Scholar
  2. 2.
    Holle JU, Laudien M, Gross WL (2010) Clinical manifestations and treatment of Wegener’s granulomatosis. Rheum Dis Clin N Am 36(3):507–526.  https://doi.org/10.1016/j.rdc.2010.05.008 CrossRefGoogle Scholar
  3. 3.
    Cotch MF, Hoffman GS, Yerg DE, Kaufman GI, Targonski P, Kaslow RA (1996) The epidemiology of Wegener’s granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheum 39(1):87–92.  https://doi.org/10.1002/art.1780390112 CrossRefPubMedGoogle Scholar
  4. 4.
    Mohammad AJ, Jacobsson LTH, Mahr AD, Sturfelt G, Segelmark M (2007) Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford) 46(8):1329–1337.  https://doi.org/10.1093/rheumatology/kem107 CrossRefGoogle Scholar
  5. 5.
    Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, Hauser T, Hellmich B, Jayne D, Kallenberg CGM, Merkel PA, Raspe H, Salvarani C, Scott DGI, Stegeman C, Watts R, Westman K, Witter J, Yazici H, Luqmani R, for the European Vasculitis Study Group (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68(3):310–317.  https://doi.org/10.1136/ard.2008.088096 CrossRefPubMedGoogle Scholar
  6. 6.
    Tsuzuki K, Fukazawa K, Takebayashi H, Hashimoto K, Sakagami M (2009) Difficulty of diagnosing Wegener’s granulomatosis in the head and neck region. Auris Nasus Larynx 36(1):64–70.  https://doi.org/10.1016/j.anl.2008.02.003 CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia-Porrua C, Amor-Dorado JC, Gonzalez-Gay MA (2001) Unilateral submandibular swelling as unique presentation of Wegener’s granulomatosis. Rheumatology (Oxford) 40(8):953–954.  https://doi.org/10.1093/rheumatology/40.8.953 CrossRefGoogle Scholar
  8. 8.
    Wiik A (2002) Rational use of ANCA in the diagnosis of vasculitis. Rheumatology (Oxford) 41(5):481–483.  https://doi.org/10.1093/rheumatology/41.5.481 CrossRefGoogle Scholar
  9. 9.
    Jennings CR, Jones NS, Dugar J, Powell RJ, Lowe J (1998) Wegener’s granulomatosis—a review of diagnosis and treatment in 53 subjects. Rhinology 36(4):188–191PubMedGoogle Scholar
  10. 10.
    McDonald TJ, DeRemee RA (1993) Head and neck involvement in Wegener’s granulomatosis (WG). Adv Exp Med Biol 336:309–313.  https://doi.org/10.1007/978-1-4757-9182-2_49 CrossRefPubMedGoogle Scholar
  11. 11.
    Martinez Del Pero M, Rasmussen N, Chaudhry A, Jani P, Jayne D (2013) Structured clinical assessment of the ear, nose and throat in patients with granulomatosis with polyangiitis (Wegener’s). Eur Arch Otorhinolaryngol 270(1):345–354.  https://doi.org/10.1007/s00405-012-2110-8 CrossRefPubMedGoogle Scholar
  12. 12.
    Hernández-Rodríguez J, Hoffman GS, Koening CL (2010) Surgical interventions and local therapy for Wegener’s granulomatosis. Curr Opin Rheumatol 22(1):29–36.  https://doi.org/10.1097/BOR.0b013e328333e9e9 CrossRefPubMedGoogle Scholar
  13. 13.
    Ono N, Niiro H, Ueda A, Sawabe T, Nishizaka H, Furugo I, Yoshizawa S, Yoshizawa S, Tsukamoto H, Kiyohara C, Tada Y, Horiuchi T (2015) Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan. Rheumatol Int 35(3):555–559.  https://doi.org/10.1007/s00296-014-3106-z CrossRefPubMedGoogle Scholar
  14. 14.
    Schirmer JH, Wright MN, Herrmann K et al (2016) 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 (Hoboken, N.J.) 68(12):2953–2963CrossRefGoogle Scholar
  15. 15.
    Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, Mahr A, Segelmark M, Cohen-Tervaert JW, Scott D (2007) Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 66(2):222–227.  https://doi.org/10.1136/ard.2006.054593 CrossRefPubMedGoogle Scholar
  16. 16.
    Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, Flossmann O, Hall C, Hollywood J, Jayne D, Jones R, Lanyon P, Muir A, Scott D, Young L, Luqmani RA (2009) Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis 68(12):1827–1832.  https://doi.org/10.1136/ard.2008.101279 CrossRefPubMedGoogle Scholar
  17. 17.
    Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage COS, Adu D (1997) Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum 40(2):371–380.  https://doi.org/10.1002/art.1780400222 CrossRefPubMedGoogle Scholar
  18. 18.
    Levey AS, Stevens LA, Schmid CH, Zhang Y(L), Castro AF III, Feldman HI, Kusek JW, Eggers P, van Lente F, Greene T, Coresh J, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612.  https://doi.org/10.7326/0003-4819-150-9-200905050-00006 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8(4):R204CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hauer HA, Bajema IM, van Houwelingen HC et al (2002) Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int 61(1):80–89.  https://doi.org/10.1046/j.1523-1755.2002.00089.x CrossRefPubMedGoogle Scholar
  21. 21.
    Rahmattulla C, de Lind van Wijngarden RA, Berden AE et al (2015) Renal function and ear, nose, throat involvement in anti-neutrophil cytoplasmic antibody-associated vasculitis: prospective data from the European Vasculitis Society clinical trials. Rheumatology (Oxford) 54(5):899–907.  https://doi.org/10.1093/rheumatology/keu357 CrossRefGoogle Scholar
  22. 22.
    Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116(6):488–498.  https://doi.org/10.7326/0003-4819-116-6-488 CrossRefPubMedGoogle Scholar
  23. 23.
    Sproson EL, Jones NS, Al-Deiri M, Lanyon P (2007) Lessons learnt in the management of Wegener’s granulomatosis: long-term follow-up of 60 patients. Rhinology 45(1):63–67PubMedGoogle Scholar
  24. 24.
    McDonald TJ, DeRemee RA (1983) Wegener’s granulomatosis. Laryngoscope 93(2):220–231CrossRefPubMedGoogle Scholar
  25. 25.
    Wojciechowska J, Krajewski W, Krajewski P, Kręcicki T (2016) Granulomatosis with polyangiitis in otolaryngologist practice: a review of current knowledge. Clin Exp Otorhinolaryngol 9(1):8–13.  https://doi.org/10.21053/ceo.2016.9.1.8 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rahne T, Clauß F, Plontke SK, Keyßer G (2017) Prevalence of hearing impairment in patients with rheumatoid arthritis, granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis), or systemic lupus erythematosus. Clin Rheumatol 36(7):1501–1510.  https://doi.org/10.1007/s10067-017-3651-4 CrossRefPubMedGoogle Scholar
  27. 27.
    Gottschlich S, Ambrosch P, Kramkowski D, Laudien M, Buchelt T, Gross WL, Hellmich B (2006) Head and neck manifestations of Wegener’s granulomatosis. Rhinology 44(4):227–233PubMedGoogle Scholar
  28. 28.
    Kornblut AD, Wolff SM, deFries HO, Fauci AS (1980) Wegener’s granulomatosis. Laryngoscope 90(9):1453–1465.  https://doi.org/10.1288/00005537-198009000-00005 CrossRefPubMedGoogle Scholar
  29. 29.
    Langford CA, Sneller MC, Hallahan CW, Hoffman GS, Kammerer WA, Talar-Williams C, Fauci AS, Lebovics RS (1996) Clinical features and therapeutic management of subglottic stenosis in patients with Wegener’s granulomatosis. Arthritis Rheum 39(10):1754–1760.  https://doi.org/10.1002/art.1780391020 CrossRefPubMedGoogle Scholar
  30. 30.
    Pavone L, Grasselli C, Chierici E, Maggiore U, Garini G, Ronda N, Manganelli P, Pesci A, Rioda WT, Tumiati B, Pavesi G, Vaglio A, Buzio C, Secondary and Primar Vasculitides (Se.Pri.Va) Study Group (2006) Outcome and prognostic factors during the course of primary small-vessel vasculitides. J Rheumatol 33(7):1299–1306PubMedGoogle Scholar
  31. 31.
    Bligny D, Mahr A, Le Toumelin P, Mouthon L, Guillevin L (2004) Predicting mortality in systemic Wegener’s granulomatosis: a survival analysis based on 93 patients. Arthritis Rheum 51(1):83–91.  https://doi.org/10.1002/art.20082 CrossRefPubMedGoogle Scholar
  32. 32.
    Mohammad AJ, Jacobsson LTH, Westman KWA, Sturfelt G, Segelmark M (2009) Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford) 48(12):1560–1565.  https://doi.org/10.1093/rheumatology/kep304 CrossRefGoogle Scholar
  33. 33.
    Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE, Nachman PH, Jennette JC, Falk RJ (2012) 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 64(10):3452–3462.  https://doi.org/10.1002/art.34562 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pagnoux C, Carette S, Khalidi NA et al (2015) Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts. Clin Exp Rheumatol 33(2 Suppl 89):S-77–S-83Google Scholar
  35. 35.
    Córdova-Sánchez BM, Mejía-Vilet JM, Morales-Buenrostro LE, Loyola-Rodríguez G, Uribe-Uribe NO, Correa-Rotter R (2016) Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clin Rheumatol 35(7):1805–1816.  https://doi.org/10.1007/s10067-016-3195-z CrossRefPubMedGoogle Scholar
  36. 36.
    Mahr A, Katsahian S, Varet H, Guillevin L, Hagen EC, Höglund P, Merkel PA, Pagnoux C, Rasmussen N, Westman K, Jayne DRW, for the French Vasculitis Study Group (FVSG) and the European Vasculitis Society (EUVAS) (2013) Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann Rheum Dis 72(6):1003–1010.  https://doi.org/10.1136/annrheumdis-2012-201750 CrossRefPubMedGoogle Scholar
  37. 37.
    Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, Hoglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Stegeman C, Walsh M, Westman K, for the European Vasculitis Study Group (2011) Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 70(3):488–494.  https://doi.org/10.1136/ard.2010.137778 CrossRefPubMedGoogle Scholar
  38. 38.
    Wallace ZS, Lu N, Unizony S, Stone JH, Choi HK (2016) Improved survival in granulomatosis with polyangiitis: a general population-based study. Semin Arthritis Rheum 45(4):483–489.  https://doi.org/10.1016/j.semarthrit.2015.07.009 CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Mara Felicetti
    • 1
  • Diego Cazzador
    • 2
  • Roberto Padoan
    • 1
  • Alfonso Luca Pendolino
    • 2
  • Chiara Faccioli
    • 2
  • Ennio Nardello
    • 2
  • Alvise Berti
    • 3
  • Marina Silvestrini
    • 4
  • Giuseppe Paolazzi
    • 3
  • Giuliano Brunori
    • 5
  • Elisabetta Zanoletti
    • 2
  • Enzo Emanuelli
    • 2
  • Alessandro Martini
    • 2
  • Franco Schiavon
    • 1
  1. 1.Operative Unit of Rheumatology, Department of Medicine DIMEDUniversity of PadovaPadovaItaly
  2. 2.Otorhinolaryngology Unit, Department of NeurosciencesUniversity of PadovaPadovaItaly
  3. 3.Rheumatology UnitSanta Chiara HospitalTrentoItaly
  4. 4.Otolaryngology UnitSanta Chiara HospitalTrentoItaly
  5. 5.Nephrology UnitSanta Chiara HospitalTrentoItaly

Personalised recommendations