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Zeitschrift für Rheumatologie

, Volume 78, Issue 3, pp 281–286 | Cite as

Relationship of ocular presentation in granulomatosis with polyangiitis to autoantibodies and disease activity

  • T. A. GheitaEmail author
  • E. M. Abd El Latif
Originalien

Abstract

Objective

The aim of this study was to assess disease characteristics, autoantibodies, and disease activity in granulomatosis with polyangiitis (GPA) patients with ocular manifestations.

Methods

The cohort included 46 GPA patients visiting the ophthalmology clinic. Ocular manifestations were recorded, clinical and slit lamp examinations were performed. The Birmingham Vasculitis Activity Score (BVAS) was recorded. Laboratory investigations and the antineutrophil cytoplasmic antibody (ANCA) assay were performed.

Results

Median age of the 22 male and 24 female patients was 44.5 (32–63) years, median disease duration 6.5 (1–16) years. Ocular manifestations were present in all patients: 12 (26.1%) had proptosis; 40 (87%) had scleritis/episcleritis, with perforation in 3 (6.5%); 33 (71.7%) had keratoconjunctivitis (KC), with acute infiltrative stromal keratitis in 11, peripheral ulcerative keratitis in 15, and sclerosing keratitis in 11 patients. Uveitis was present in 11 (23.9%) and retinal changes including vasculitis, exudates, and hemorrhage were present in 7 (15.2%). Blurred vision was present in 43 (93.5%) patients and 2 (4.3%) had vision loss. Glaucoma was present in 4 (8.7%) and hypotony in 2 (4.3%) patients. Involvement was bilateral in 32 (69.6%) patients. Rheumatoid factor (RF) was positive in 56.5% and significantly associated with uveitis (p = 0.04), while antinuclear antibody (ANA) was positive in 45.7% and significantly associated with KC (p = 0.04). BVAS tended to be higher in patients with uveitis (p = 0.49).

Conclusion

Ocular involvement must be considered in all GPA patients and referral to an experienced ophthalmologist is mandatory for proper management and improved outcome of such a rare systemic disease. ANA and RF positivity may raise suspicion for KC or uveitis, respectively. There was a remarkable association between uveitis and disease activity.

Keywords

Anti-neutrophil cytoplasmic antibody-associated vasculitis Rheumatoid factor Uveitis Keratoconjunctivitis Ophthalmologists 

Zusammenhang zwischen okulärer Manifestation bei Granulomatose mit Polyangiitis und Autoantikörpern sowie Krankheitsaktivität

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war es, Krankheitsmerkmale, Autoantikörper und Krankheitsaktivität bei Patienten mit Granulomatose und Polyangiitis (GPA) bei Vorliegen okulärer Manifestationen zu untersuchen.

Methoden

Die Kohorte umfasste 46 GPA-Patienten der ophthalmologischen Klinik. Die okulären Manifestationen wurden dokumentiert, es erfolgte eine klinische und eine Spaltlampenuntersuchung. Außerdem wurde der Birmingham Vasculitis Activity Score (BVAS) ermittelt. Neben anderen Laboruntersuchungen wurde die Bestimmung der antineutrophilen zytoplasmatischen Antikörper (ANCA) durchgeführt.

Ergebnisse

Das Durchschnittsalter der 22 männlichen und 24 weiblichen Patienten betrug 44,5 (32–63) Jahre, die mittlere Krankheitsdauer lag bei 6,5 (1–16) Jahren. Bei allen Patienten lagen okuläre Manifestationen vor: Bei 12 (26,1 %) eine Proptosis bulbi; 40 (87 %) wiesen eine Skleritis/Episkleritis auf, 3 mit Perforation 3 (6,5 %); bei 33 (71,7 %) bestand eine Keratokonjunktivitis (KC), mit akuter infiltrativer stromaler Keratitis in 11 Fällen, mit peripherer ulzerativer Keratitis bei 15 und mit sklerosierender Keratitis bei 11 Patienten. Eine Uveitis lag bei 11 Patienten vor (23,9 %), und Retinaveränderungen einschließlich Vaskulitis, Exudaten und Blutungen bestanden in 7 Fällen (15,2 %). Verschwommensehen bestand bei 43 (93,5 %) Patienten, und in 2 Fällen (4,3 %) lag eine Einschränkung der Sehkraft vor. Ein Glaukom bestand in 4 (8,7 %) und eine Hypotonie in 2 (4,3 %) Fällen. Bei 32 (69,6 %) Patienten war die Beteiligung bilateral. Der Rheumafaktor (RF) war in 56,5 % der Fälle positiv und in signifikanter Weise mit einer Uveitis assoziiert (p = 0,04), während antinukleäre Antikörper (ANA) in 45,7 % der Fälle positiv und signifikant mit einer KC assoziiert waren (p = 0,04). Der BVAS war bei Patienten mit Uveitis tendenziell höher (p = 0,49).

Schlussfolgerung

Die okuläre Beteiligung muss bei allen GPA-Patienten berücksichtigt werden, eine Überweisung an einen erfahrenen Ophthalmologen ist zwingend für die angemessene Versorgung und einen besseren Verlauf bei einer solchen seltenen systemischen Erkrankung. ANA- und RF-Positivität können den Verdacht auf eine KC oder Uveitis wecken. Es bestand eine beachtliche Assoziation zwischen einer Uveitis und der Krankheitsaktivität.

Schlüsselwörter

Mit antineutrophilen zytoplasmatischen Antikörpern assoziierte Vaskulitis Rheumafaktor Uveitis Keratokonjunktivitis Ophthalmologen 

Notes

Compliance with ethical guidelines

Conflict of interest

T. A. Gheita and E. M. Abd El Latif declare that they have no competing interests.

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 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants from whom identifying information is included in this article.

References

  1. 1.
    Kubaisi B, Samra AK, Foster CS (2016) Granulomatosis with polyangiitis (Wegener’s disease): an updated review of ocular disease manifestations. Intractable Rare Dis Res 5(2):61–69CrossRefGoogle Scholar
  2. 2.
    Ntatsaki E, Watts RA, Scott DG (2010) Epidemiology of ANCA-associated vasculitis. Rheum Dis Clin North Am 36:447–461CrossRefGoogle Scholar
  3. 3.
    Andrews M, Edmunds M, Campbell A et al (1990) Systemic vasculitis in the 1980s ? is there an increasing incidence of Wegener’s granulomatosis and microscopic polyarteritis? J R Coll Physicians Lond 24:284–288PubMedPubMedCentralGoogle Scholar
  4. 4.
    Chung S, Monach PA (2017) Anti-neutrophil cutoplasmic antibody-associated vasculitis. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR (eds) Kelley and Firestein’s textbook of rheumatology. Elsevier, Philadelphia, pp 1541–1558 (Chapter 89)CrossRefGoogle Scholar
  5. 5.
    Cisternas M, Soto L, Jacobelli S et al (2005) Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients. Rev Med Chil 133(3):273–278CrossRefGoogle Scholar
  6. 6.
    Rothschild PR, Pagnoux C, Seror R et al (2013) Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Semin Arthritis Rheum 42(5):507–514CrossRefGoogle Scholar
  7. 7.
    Gheita TA, Samad HM, Mahdy MA (2014) Pattern of primary vasculitis with peripheral ischemic manifestations: report of a case series and role of vascular surgery. Curr Rheumatol Rev 10(2):126–130CrossRefGoogle Scholar
  8. 8.
    Niederkorn JY (2006) See no evil, hear no evil, do no evil: the lessons of immune privilege. Nat Immunol 7:353–359CrossRefGoogle Scholar
  9. 9.
    Rosenbaum JT (2017) The eye and rheumatic diseases. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR (eds) Kelley and Firestein’s textbook of rheumatology. Elsevier, Philadelphia, pp 645–653 (Chapter 44)CrossRefGoogle Scholar
  10. 10.
    Leavitt RY, Fauci AS, Bloch DA et al (1990) The American College of Rheumatology 1990 criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum 33:1101–1107CrossRefGoogle Scholar
  11. 11.
    Luqmani RA, Bacon PA, Moots RJ et al (1994) Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 87:671–678PubMedGoogle Scholar
  12. 12.
    Wang T, Shi W, Fan T, Wan X, Chen YH, Ruan Q (2016) c‑Rel is required for the induction of pTregs in the eye but not in the Gut Mucosa. Immunol Invest 45(8):776–786CrossRefGoogle Scholar
  13. 13.
    Aldasoro-Cáceres V, Aldasoro-Cáceres I, Pérez-Moreiras JV et al (2014) C‑ANCA positive necrotising scleritis and multiple sclerosis compatible with ocular Wegener: treatment with rituximab. Arch Soc Esp Oftalmol 89(1):31–34CrossRefGoogle Scholar
  14. 14.
    Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW et al (1992) Wegener’s granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488–498CrossRefGoogle Scholar
  15. 15.
    Torres RM, Herreras JM, Becerra E et al (2004) Ocular presentation in Wegener granulomatosis. Arch Soc Esp Oftalmol 79(3):135–138CrossRefGoogle Scholar
  16. 16.
    García C, Voorduin S, Pedroza-Seres M (2006) Diagnosis of Wegener’s granulomatosis in patients with ocular inflamatory disease. Gac Med Mex 142(6):477–482PubMedGoogle Scholar
  17. 17.
    Cogan D (1995) Corneoscleral lesions in periarteritis nodosa and Wegener’s granulomatosis. Trans Am Ophthalmol Soc 53:321–342Google Scholar
  18. 18.
    Spalton DJ, Graham EM, Page NG et al (1981) Ocular changes in limited forms of Wegener’s granulomatosis. Br J Ophthalmol 1981(65):553–563CrossRefGoogle Scholar
  19. 19.
    Sadiq SA, Jennings CR, Jones NS et al (2000) Wegener’s granulomatosis: the ocular manifestations revisited. Orbit 19(4):253–261CrossRefGoogle Scholar
  20. 20.
    Holle JU, Voigt C, Both M et al (2013) Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage. Rheumatology (Oxford) 52:875–882CrossRefGoogle Scholar
  21. 21.
    Jinnah HA, Dixon A, Brat DJ, Hellmann DB (1997) Review chronic meningitis with cranial neuropathies in Wegener’s granulomatosis. Case report and review of the literature. Arthritis Rheum 40(3):573–577CrossRefGoogle Scholar
  22. 22.
    Akpek EK, Thorne JE, Qazi FA et al (2004) Evaluation of patients with scleritis for systemic disease. Ophthalmology 111(3):501–506CrossRefGoogle Scholar
  23. 23.
    Cocho L, Gonzalez-Gonzalez LA, Molina-Prat N et al (2016) Scleritis in patients with granulomatosis with polyangiitis (Wegener). Br J Ophthalmol 100(8):1062–1065CrossRefGoogle Scholar
  24. 24.
    Sainz de la Maza M, Foster CS, Jabbur NS (1995) Scleritis associated with systemic vasculitic diseases. Ophthalmology 102:687–692CrossRefGoogle Scholar
  25. 25.
    Wieringa WG, Wieringa JE, ten Dam-van Loon NH et al (2013) Visual outcome, treatment results, and prognostic factors in patients with scleritis. Ophthalmology 120:379–386CrossRefGoogle Scholar
  26. 26.
    Fortney AC, Chodosh J (2002) Conjunctival ulceration in recurrent Wegener granulomatosis. Cornea 21(6):623–624CrossRefGoogle Scholar
  27. 27.
    Messmer EM, Foster CS (1999) Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol 43:379–396CrossRefGoogle Scholar
  28. 28.
    Palmowski AM, Hille K, Ruprecht KW (1994) Non-syphilitic interstitial keratitis and inner ear deafness in the initial phase of Wegener’s granulomatosis. Klin Monbl Augenheilkd 205:364–367CrossRefGoogle Scholar
  29. 29.
    Cassan SM, Coles DT, Harrison EG Jr. (1970) The concept of limited forms of Wegener’s granulomatosis. Am J Med 49:366–379CrossRefGoogle Scholar
  30. 30.
    Straatsma BR (1957) Ocular manifestations of Wegener’s granulomatosis. Am J Ophthalmol 144:789–799CrossRefGoogle Scholar
  31. 31.
    Watkins AS, Kempen JH, Choi D et al (2009) Ocular disease in patients with ANCA-positive vasculitis. J Ocul Biol Dis Infor 3:12–19CrossRefGoogle Scholar
  32. 32.
    du Huong LT, Tran TH, Piette JC (2006) Granulomatous uveitis revealing Wegener’s granulomatosis. J Rheumatol 33:1209–1210Google Scholar
  33. 33.
    Woo TL, Francis IC, Wilcsek GA et al (2001) Australasian orbital and adnexal Wegener’s granulomatosis. Ophthalmology 108:1535–1543CrossRefGoogle Scholar
  34. 34.
    Harper SL, Letko E, Samson CM et al (2001) Wegener’s granulomatosis: the relationship between ocular and systemic disease. J Rheumatol 28:1025–1032PubMedGoogle Scholar
  35. 35.
    Schonermarck U, Lamprecht P, Csernok E et al (2001) Prevalence and spectrum of rheumatic diseases associated with proteinase 3‑antineutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Rheumatology 40:178–184CrossRefGoogle Scholar
  36. 36.
    Falk RJ, Hogan S, Carey TS et al (1990) Clinical course of anti-neutrophil cytoplasmic autoantibodyassociated glomerulonephritis and systemic vasculitis. The glomerular disease collaborative network. Ann Intern Med 113:656–663CrossRefGoogle Scholar
  37. 37.
    Power WJ, Rodriguez A, Neves RA et al (1995) Disease relapse in patients with ocular manifestations of Wegener granulomatosis. Ophthalmology 102(1):154–160CrossRefGoogle Scholar
  38. 38.
    Pagnoux C, Hogan SL, Chin H et al (2008) Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum 58:2908–2918CrossRefGoogle Scholar
  39. 39.
    Savige JA, Chang L, Wilson D et al (1996) Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Rheumatol Int 16(3):109–114CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Rheumatology and Clinical Immunology, Faculty of MedicineCairo UniversityCairoEgypt
  2. 2.Ophthalmology Department, Faculty of MedicineAlexandria UniversityAlexandriaEgypt

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