Impact of seasons on occurance and flares of granulomatosis with polyangitis: Implications from a tertiary center from central Anatolia

##plugins.themes.themeTen.article.main##

Gülşah Soytürk
Hatice Ecem Konak
Pınar Akyüz Dağlı
Rezan Koçak Ulucaköy
Ebru Atalar
Esra Kayacan Erdoğan
Hakan Babaoğlu
Berkan Armağan
Kevser Orhan
İsmail Dogan
Yüksel Maraş
Ahmet Omma
Şükran Erten
Orhan Küçükşahin
Serdar Can Güven

Keywords

AAV (ANCA-associated vasculitis), , environmental risks,, etiology, vasculitis

Abstract

Abstract


Background and aim: The etiology of granulomatosis with polyangiitis (GPA) remains under discussion. This study aims to explore patterns of organ involvement, ANCA antibody profiles, seasonal attack rates, and their interrelationship among patients diagnosed with ANCA-associated vasculitis (AAV) in central Anatolia, shedding light on the multifactorial etiology involving drugs, genetics and environmental factors.


 


Methods: We conducted a retrospective study involving patients aged 18 to 65 diagnosed with GPA and receiving care at Ankara Bilkent City Hospital Rheumatology Clinic. Diagnosis criteria followed the 2012 Chapel Hill Consensus Conference guidelines and the 2022 American College of Rheumatology/European Association of Rheumatology Societies classification for AAV. Patient data included demographics, antibody test results, seasons of diagnosis and flare, affected organs, and Birmingham Vasculitis Activity Score (BVAS). Organ involvement was determined based on biopsy findings or established criteria.


 


Results: Our study included 75 patients, with the majority exhibiting cANCA-IFA positivity (94.7%) and PR3-ANCA ELISA positivity (98.3%). During follow-up, 70.7% experienced their first flare, with 37.7% experiencing a second flare. Lung involvement was most common at diagnosis and during flares, followed by ear-nose-throat and renal involvement. Seasonal analysis revealed peaks in disease onset in March, November, and April, with flares more common in September, May, October, and November. Autumn was the most common season for the first flare.


 


Conclusions: This study provides novel insights into ANCA-associated vasculitis epidemiology in central Anatolia. Our findings underscore the intricate seasonal variation and infectious triggers of GPA exacerbations, highlighting the importance of tailored management strategies to mitigate disease flares.


 

Abstract 0 |

References


1. Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis. 2022;81(3):315-320.
2. Radice A, Sinico RA. Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity. 2005;38(1):93-103.
3. Fries JF, Hunder GG, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis: Summary. Arthritis Rheum. 1990;33(8):1135-1136.
4. Jennette JC. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013;17(5):603-606.
5. Watts, R., Lane, S., Hanslik, T., et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Annals of the rheumatic diseases. 2007;66(2), 222–227. https://doi.org/10.1136/ard.2006.054593
6. Craven A, Robson J, Ponte C, et al. ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS). Clin Exp Nephrol. 2013;17(5):619-621.
7. Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367(3):214-223.
8. Nakazawa D, Masuda S, Tomaru U, Ishizu A. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nat Rev Rheumatol. 2019;15(2):91-101.
9. Gupta N, Mahendran AJ, Chakrabarti S, Agrawal S. Microscopic polyangiitis in a case of silica exposure: a rare presentation. Monaldi Arch Chest Dis Arch Monaldi Mal Torace. 2019;89(3).
10. Rao N, Bendall A, Lanteri M. ANCA vasculitis and IgA nephropathy linked to silica exposure. Occup Med Oxf Engl. 2020;70(6):445-448.
11. Draibe J, Rodó X, Fulladosa X, et al. Seasonal variations in the onset of positive and negative renal ANCA-associated vasculitis in Spain. Clin Kidney J. 2018;11(4):468-473.
12. Li J, Cui Z, Long JY, et al. The frequency of ANCA-associated vasculitis in a national database of hospitalized patients in China. Arthritis Res Ther. 2018;20(1):226.
13. Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022;81(3):309-314.
14. Hogan SL, Satterly KK, Dooley MA,et al. Silica Exposure in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis and Lupus Nephritis. J Am Soc Nephrol. 2001;12(1):134.
15. Nachman PH, Hogan SL, Jennette JC, Falk RJ. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol JASN. 1996;7(1):33-9.
16. Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007;66(5):605-617.
17. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 02 2024;83(1):30-47.
18. Mahr A, Artigues N, Coste J, et al. Seasonal variations in onset of Wegener’s granulomatosis: increased in summer? J Rheumatol. 2006;33(8):1615-1622.
19. Kemna MJ, Cohen Tervaert JW, Broen K, Timmermans SAMEG, van Paassen P, Damoiseaux JGMC. Seasonal Influence on the Risk of Relapse at a Rise of Antineutrophil Cytoplasmic Antibodies in Vasculitis Patients with Renal Involvement. J Rheumatol. 2017;44(4):473-481.
20. Falk RJ, Hogan S, Carey TS, Jennette JC. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med. 1990;113(9):656-663.
21. Raynauld JP, Bloch DA, Fries JF. Seasonal variation in the onset of Wegener’s granulomatosis, polyarteritis nodosa and giant cell arteritis. J Rheumatol. 1993;20(9):1524-1526.
22. Tidman M, Olander R, Svalander C, Danielsson D. Patients hospitalized because of small vessel vasculitides with renal involvement in the period 1975-95: organ involvement, anti-neutrophil cytoplasmic antibodies patterns, seasonal attack rates and fluctuation of annual frequencies. J Intern Med. Ağustos 1998;244(2):133-141.
23. Aries PM, Herlyn K, Reinhold-Keller E, Latza U. No seasonal variation in the onset of symptoms of 445 patients with Wegener’s granulomatosis. Arthritis Rheum. 2008;59(6):904.
24. Koldingsnes W, Nossent H. Epidemiology of Wegener’s granulomatosis in northern Norway. Arthritis Rheum. 2000;43(11):2481-2487.
25. Lane SE, Watts RA, Scott DGI. Seasonal variations in onset of Wegener’s granulomatosis: increased in summer? J Rheumatol. 2007;34(4):889-90; author reply 890.
26. Albert D, Clarkin C, Komoroski J, Brensinger CM, Berlin JA. Wegener’s granulomatosis: Possible role of environmental agents in its pathogenesis. Arthritis Care Res. 2004;51(4):656-64.
27. Reinhold‐Keller E, Herlyn K, Wagner‐Bastmeyer R, et al. No difference in the incidences of vasculitides between north and south Germany: first results of the German vasculitis register. Rheumatology. 2002;41(5):540-549.
28. Yoon T, Ahn SS, Pyo JY, Song JJ, Park YB, Lee SW. Serum vitamin D level correlates with disease activity and health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis. Z Für Rheumatol. 2022;81(1):77-84.
29. DeRemee RA, McDonald TJ, Weiland LH. Wegener’s granulomatosis: observations on treatment with antimicrobial agents. Mayo Clin Proc. 1985;60(1):27-32.
30. Uslu Yurteri E, Sezer S, Torgutalp M, et al. The factors predicting development of serious infections in ANCA-associated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis. 2023;40(2):e2023015.
31. Kronbichler A, Kerschbaum J, Mayer G. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review. J Immunol Res. 2015;2015:e858027.
32. Salmela A, Rasmussen N, Tervaert JWC, Jayne DRW, Ekstrand A, on behalf of the European Vasculitis Study Group. Chronic nasal Staphylococcus aureus carriage identifies a subset of newly diagnosed granulomatosis with polyangiitis patients with high relapse rate. Rheumatology. 2017;56(6):965-972.
33. van Timmeren MM, Heeringa P, Kallenberg CGM. Infectious triggers for vasculitis. Curr Opin Rheumatol. 2014;26(4):416.
34. Ishiguro T, Takayanagi N, Takaku Y, Kagiyama N, Kurashima K, Sugita Y. Combined Allergic Bronchopulmonary Aspergillosis and Eosinophilic Granulomatosis with Polyangiitis: Three Cases and a Review of the Literature. Intern Med Tokyo Jpn. 2016;55(7):793-797.
35. Kuwabara G, Yamada K, Tanaka K, et al. Muscle Biopsy-proven Drug-induced Microscopic Polyangiitis in a Patient with Tuberculosis. Intern Med. 2023;62(1):129-133.
36. Fujita M, Hatachi S, Yagita M. Acute Chlamydia pneumoniae infection in the pathogenesis of autoimmune diseases. Lupus. 2009;18(2):164-168.
37. Tervaert JWC. ANCA testing in monitoring the activity of the disease. Kidney Blood Press Res. 2003;26(4):226-230.
38. Sanders JSF, Huitma MG, Kallenberg CGM, Stegeman CA. Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment. Rheumatol Oxf Engl. 2006;45(6):724-729.
39. Slot MC, Tervaert JWC, 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. 2004;51(2):269-273.
40. Huugen D, Xiao H, van Esch A, et al. Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-alpha. Am J Pathol. 2005;167(1):47-58.
41. 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. 1994;120(1):12-17.
42. Tervaert JW, van der Woude FJ, Fauci AS, et al. Association between active Wegener’s granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989;149(11):2461-2465.
43. Tervaert JW, Huitema MG, Hené RJ, et.al. Prevention of relapses in Wegener’s granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet Lond Engl. 1990;336(8717):709-711.