Received: 28.08.2022; Accepted: 31.10.2022; Published on-line: 21.12.2022
Ophthalmological involement and laboratory changes in patients with ANCA-associated vasculitis and polyarteritis nodosa
O. Iaremenko, L. Petelytska
Bogomolets National Medical University; Kyiv (Ukraine)
Background. Ophthalmic involvement (OI) is an early manifestation of systemic vasculitis and may lead to blindness.
Purpose. Aim of the study was to identify the frequencies and patterns of OI in patients with ANCA-associated vasculitis (AAV) and polyarteritis nodosa (PAN) and evaluate the laboratory changes depending on OI.
Material and Methods. This work included retrospective study (112 patients with PAN and 80 patients with AAV) and prospective cohort study, which evaluated serum levels of endothelin-1 (ET-1) in 36 patients and 26 healthy сontrols.
Results. OI at diagnosis in AAV occurred 4 times more often compared to PAN and consisted of conjunctivitis/episcleritis (16% AAV patients), optic neuropathy (5% PAN patients), orbital mass, uveitis, scleritis, epiphora or dry eyes. OI was more commonly detected in PR3-ANCA(+) vs PR3-ANCA(-) patients. The levels of ET-1 were elevated in patients without OI compared with control group and patients with OI, but ability of ET-1 to differentiate such patients was poor.
Conclusion. The most common OI in patients with AAV was episcleritis. Optic neuropathy was the only manifestation of OI in patients with PAN. OI were more commonly detected in PR3-ANCA(+) vs PR3-ANCA(-) patients. The serum levels of ET-1 were significantly elevated in patients without OI compared with patients with OI and control group, but its diagnostic value was not approved in the ROC analysis.
Keywords: eye involvement, anti-neutrophil cytoplasmic antibody-associated vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa
1.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 and rheumatism. 2013; 65(1): 1–11.
2.Millet A, Pederzoli-Ribeil M, Guillevin L, Witko-Sarsat V, Mouthon L. Antineutrophil cytoplasmic antibody-associated vasculitides: is it time to split up the group? Annals of the rheumatic diseases. 2013; 72(8): 1273–1279.
3.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 and rheumatism. 2012; 64(10): 3452–3462.
4.Rothschild P R, Pagnoux C, Seror R, Brézin AP, Delair E, Guillevin L. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Seminars in arthritis and rheumatism. 2013; 42(5): 507–514.
5.Ungprasert P, Crowson CS, Cartin-Ceba R, Garrity JA, Smith WM, Specks U et al. Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study. Rheumatology (Oxford, England). 2017; 56(10) : 1763–1770.
6.Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis and rheumatism. 2010; 62(2): 616–626.
7.Pakrou N, Selva D, Leibovitch I. Wegener's granulomatosis: ophthalmic manifestations and management. Seminars in arthritis and rheumatism. 2006; 35(5): 284–292.
8.Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD et al. Wegener granulomatosis: an analysis of 158 patients. Annals of internal medicine. 1992; 116(6): 488–498.
10.Watkins AS, Kempen JH, Choi D, Liesegang TL, Pujari SS, Newcomb C et al. Ocular disease in patients with ANCA-positive vasculitis. Journal of ocular biology, diseases, and informatics. 2009; 3(1): 12–19.
11.Miyanaga M, Takase H, Ohno-Matsui K. Anti-Neutrophil Cytoplasmic Antibody-Associated Ocular Manifestations in Japan: A Review of 18 Patients. Ocular immunology and inflammation. 2021; 29(5): 991–996.
12.Savige J, Davies D, Falk RJ, Jennette JC, Wiik A. Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features. Kidney international. 2000; 57(3): 846–862.
13.Sugiyama T. Involvement of Endothelin-1 in the Pathophysiology of Normal-Tension Glaucoma. International Journal of Ophthalmic Research. 2015; 1(2): 36-40.
14.Ohguro H, Mashima Y, Nakazawa M. Low levels of plasma endothelin-1 in patients with retinitis pigmentosa. Clinical ophthalmology (Auckland, N.Z.). 2010; 4: 569–573.
15.Lightfoot RW Jr, Michel BA, Bloch DA, Hunder GG, Zvaifler NJ, McShane DJ et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis and rheumatism. 1990; 33(8): 1088–1093.
16.Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis and rheumatism. 1990; 33(8): 1101–1107.
17.Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis and rheumatism. 1990; 33(8): 1094–1100.
18.Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Annals of the rheumatic diseases. 2009; 68(12): 1827–1832.
19.Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A. et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry. Clinical rheumatology. 2019 ; 38(9): 2553–2563.
20.Solans-Laqué R, Fraile G, Rodriguez-Carballeira M, Caminal L, Castillo MJ, Martínez-Valle F et al. Spanish Registry of systemic vasculitis (REVAS) from the Autoimmune Diseases Study Group (GEAS) of the Spanish Society of Internal Medicine (SEMI) (2017). Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: Impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity. Medicine. 2017; 96(8): e6083.
21.Mahr A, Katsahian S, Varet H, Guillevin L, Hagen EC, Höglund P. et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Annals of the rheumatic diseases. 2013; 72(6): 1003–1010.
22.Martinez-Morillo М, Grados D. Granulomatosis With Polyangiitis (Wegener). Description of 15 Cases. Reumatol Clin. 2012; 8: 15–19.
23.Holle JU, Gross WL, Latza U, Nölle B, Ambrosch P, Heller M. et al. Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades. Arthritis and rheumatism. 2011; 63(1): 257–266.
24.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 and rheumatism. 2003; 48(8): 2299–2309.
25.Guillevin L, Durand-Gasselin B, Cevallos R, Gayraud M, Lhote F, Callard P et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis and rheumatism. 1999; 42(3): 421–430.
26.Durel CA, Hot A, Trefond L, Aumaitre O, Pugnet G, Samson M et al. Orbital mass in ANCA-associated vasculitides: Data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients. Rheumatology. 2019; 58(9): 1565–1573.
27.Schmidt J, Pulido JS, Matteson EL. Ocular manifestations of systemic disease: Antineutrophil cytoplasmic antibody-associated vasculitis. Current Opinion in Ophthalmology. 2011; 22(6): 489–495.
28.Petelytska L, Iaremenko O, Iaremenko K. FRI0288 Ophthalmological manifestations and endothelin-1 plasma levels in patients with systemic necrotizing vasculitis (SNV)Annals of the Rheumatic Diseases. 2019;78:824-825.
Information about authors and disclosure of information
Corresponding author: Liubov Petelytska – firstname.lastname@example.org.
Authors’ contributions: Oleg Iaremenko contributed to the idea for the article. Material preparation and data analysis were performed by Liubov Petelytska and Oleg Iaremenko. The first draft of the manuscript was written by Liubov Petelytska and Oleg Iaremenko commented on previous versions of the manuscript. Two authors read and approved the final manuscript.
Conflict of interest: The authors have declared that no competing interests exist.
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Authors fulfilled the ICMJE authorship criteria.
Funding information: This research does not received specific grant from any funding agency in the public, commercial or not-for -profit sector.