Survey of Ophthalmology
Volume 55, Issue 5 , Pages 429-444 , September 2010

Wegener's Granulomatosis: Clinical Manifestations, Differential Diagnosis, and Management of Ocular and Systemic Disease

  • Ahmad B. Tarabishy, MD

      Affiliations

    • Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA
  • ,
  • Mark Schulte, MD

      Affiliations

    • Division of Rheumatology, Case Western Reserve University, Cleveland, Ohio, USA
  • ,
  • George N. Papaliodis, MD

      Affiliations

    • Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
  • ,
  • Gary S. Hoffman, MD

      Affiliations

    • Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio, USA
    • Corresponding Author InformationReprint address: Gary S. Hoffman, MD, Department of Rheumatic and Immunologic Disease, Cleveland Clinic. 9500 Euclid Avenue, Cleveland, OH.

References 

  1. Alloway JA, Cupps TR. High–dose methylprednisolone for retro-orbital Wegener's granulomatosis. J Rheumatol. 1993;20:752–754
  2. Belden CJ, Hamed LM, Mancuso AA. Bilateral isolated retrobulbar optic neuropathy in limited Wegener's granulomatosis. J Clin Neuroophthalmol. 1993;13:119–123
  3. Bertelmann E, Liekfeld A, Pleyer U, et al. Cytomegalovirus retinitis in Wegener's granulomatosis: case report and review of the literature. Acta Ophthalmol Scand. 2005;83:258–261
  4. Black RL, Oglesby RB, von Sallmann L, et al. Posterior subcapsular cataracts inducted by glucocorticoids in patients with rheumatoid arthritis. JAMA. 1960;174:166–171
  5. Blaise P, Robe-Collignon N, Andris C, Rakic JM. Wegener's granulomatosis and posterior ischemic optic neuropathy: atypical associated conditions. Eur J Intern Med. 2007;18:326–327
  6. Bullen CL, Liesegang TJ, McDonald TJ, et al. Ocular complications of Wegener's granulomatosis. Ophthalmology. 1983;90:279–290
  7. Carlson JA, Cavaliere LF, Grant-Kels JM. Cutaneous vasculitis: diagnosis and management. Clin Dermatology. 2006;24:414–429
  8. Cassells-Brown A, Morrell AJ, Davies BR, et al. Wegener's granulomatosis causing lid destruction: a further sight-threateneing complication. Eye. 2003;17:652–654
  9. Charles SJ, Meyer PAR, Watson PG. Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease. Br J Ophthalmol. 1991;75:201–207
  10. Chiquet C, Lumbroso L, Denis P, et al. Acute posterior multifocal placoid pigment epitheliopathy associated with Wegener's granulomatosis. Retina. 1999;19:309–313
  11. Courcoutsakis NA, Langford CA, Sneller MC, et al. Orbital involvement in Wegener's granulomatosis: MR findings in 12 patients. J Comput Assist Tomogr. 1997;27:452–458
  12. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:2461–2469
  13. De Silva DJ, Cole C, Luthert P, et al. Masked orbital abscess in Wegener's granulomatosis. Eye. 2007;21:246–248
  14. Finkielman JD, Merkel PA, Schroeder D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener's granulomatosis. Ann Intern Med. 2007;147:611–619
  15. Fortney AC, Chodosh J. Conjunctival ulceration in recurrent Wegener granulomatosis. Cornea. 2002;21:623–624
  16. Francois J. Glucocorticoid glaucoma. Ophthalmologica. 1984;188:76–81
  17. Freidlin J, Wong IG, Acharya N. Rituximab treatment for peripheral ulcerative keratitis associated with Wegener's granulomatosis. Br J Ophthalmol. 2007;91:1414
  18. Ghanem RC, Chang N, Aoki L, et al. Vasculitis of the lacrimal sac wall in Wegener granulomatosis. Ophthal Plast Reconstr Surg. 2004;20:254–257
  19. Gordon LK, Eggena M, Holland GN, et al. pANCA antibodies in patients with anterior uveitis: identification of a marker antibody usually associated with ulcerative colitis. J Clin Immunol. 1998;18:264–271
  20. Gordon LK, Eggena M, Targan SR, et al. Definition of ocular antigens in ciliary body and retinal ganglion cells by the marker antibody pANCA. Invest Ophthalmol Vis Sci. 1999;40:1250–1255
  21. Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome: Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999;78:26–37
  22. Haimovici R, Koh S, Gagnon DR, et al. Risk factors for central serous chorioretinopathy. Ophthalmology. 2004;111:244–249
  23. Harman LE, Margo CE. Wegener's granulomatosis. Surv Ophthalmol. 1998;42:458–480
  24. Harper SL, Letko E, Samson CM, et al. Wegener's granulomatosis: the relationship between ocular and systemic disease. J Rheumatol. 2001;28:1025–1032
  25. Haynes BF, Fishman ML, Fauci AS, et al. The ocular manifestations of Wegener's granulomatosis: fifteen years experience and review of the literature. Am J Med. 1977;63:131–141
  26. Hoffman GS. Immunosuppressive therapy is always required for the treatment of Wegener's granulomatosis. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13:249–252
  27. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–498
  28. Hoffman GS, Specks U. Antineutrophil cytoplasmic antibodies. Arthritis Rheum. 1998;41:1521–1537
  29. Huong Du LT, Tran TH, Piette JC. Granulomatous uveitis revealing Wegener's granulomatosis. J Rheumatol. 2006;33:1209–1210
  30. Iida T, Spaide RF, Kantor J. Retinal and choroidal arterial occlusion in Wegener's granulomatosis. Am J Ophthalmol. 2002;133:151–152
  31. Jabs DA, Mudun A, Dunn JP, et al. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000;130:469–476
  32. Janknecht P, Mittelviefhaus H, Loffler KU. Sclerochoroidal granuloma in Wegener's granulomatosis simulating a uveal melanoma. Retina. 1995;15:150–153
  33. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44
  34. Jones RB, Tervaert JWC, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363:211–220
  35. Kain R, Exner M, Brandes R, et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med. 2008;14:1088–1096
  36. Kalina PH, Lie JT, Campbell RJ, Garrity JA. Diagnostic value and limitations or orbital biopsy in Wegener's granulomatosis. Ophthalmology. 1992;99:120–124
  37. Kamei M, Yasuhara T, Tei M, et al. Vitreous hemorrhage from a ciliary granuloma associated with Wegener granulomatosis. Am J Ophthalmol. 2001;132:924–926
  38. Kassan H, Cohavy O, Rosenbaum JT, et al. Uveitis seroreactivity to candidate pANCA antigens: mycobacterial HupB and histone H1(69–171). Ocul Immunol Inflamm. 2005;13:191–198
  39. Keogh KA, Wylam ME, Stone JH, et al. Induction of remission B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic-antibody associated vasculitis. Arthritis Rheum. 2005;52:262–268
  40. Keogh KA, Ytterberg SR, Fervenza FC, et al. Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med. 2006;173:180–187
  41. Khan SA, Subla MR, Behl D, et al. Outcome of patients with small-vessel vasculitis admitted to a medical ICU. Chest. 2007;131:972–976
  42. Kwan AS, Rose GE. Lacrimal drainage surgery in Wegener's granulomatosis. Br J Ophthalmol. 2000;84:329–331
  43. Langford CA, Hoffman GS. Wegener's granulomatosis. Thorax. 1999;54:629–637
  44. Langford CA, Talar-Williams C, Barron KS, et al. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rates of relapse. Am J Med. 2003;114:463–469
  45. Leavitt JA, Butrus SI. Wegener's granulomatosis presenting as dacryoadenitis. Cornea. 1991;10:542–545
  46. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the diagnosis of Wegener's granulomatosis. Arthritis Rheum. 1990;33:1101–1107
  47. Levy-Clarke G, Ding X, Gangaputra S, et al. Recalcitrant granulomatous sclerouveitis in a patient with granulomatous ANCA-associated vasculitis. Ocul Immunol Inflamm. 2009;17:83–87
  48. Levy-Clarke GA, Nussenblatt R. Retinal vasculitis. Int Ophthalmol Clin. 2005;45:99–113
  49. Loke YK, Tan MH. An unusual case of Wegener's granulomatosis. Med J Malaysia. 1998;53:107–109
  50. Loredo A, Rodrigues RS, Murillo L. Cataracts after short-term corticosteroid treatment. N Engl J Med. 1972;286:160
  51. Lovelace K, Cannon TC, Flynn S. Optic neuropathy in a patient with Wegener's granulomatosis. J Ark Med Soc. 2004;100:428–429
  52. Lutt JR, Lim LL, Phal PM, et al. Orbital inflammatory disease. Semin Arthritis Rheum. 2008;37:207–222
  53. Meier FM, Messmer EP, Bernauer W. Wegener's granulomatosis as a cause of cicatrizing conjunctivitis. Br J Ophthalmol. 2001;85:628
  54. Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005;142:620–626
  55. Messmer EM, Foster CS. Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol. 1999;43:379–396
  56. Mirza S, Raghu Ram AR, et al. Central retinal artery occlusion and bilateral choroidal infarcts in Wegener's granulomatosis. Eye. 1999;13:374–376
  57. Miserocchi E, Waheed NK, Baltatzis S, et al. Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis. Am J Ophthalmol. 2001;132:923–924
  58. Niskopoulou M, Du Toit N. Optic neuritis as a feature of Wegener's granulomatosis. Eye. 2002;16:320–321
  59. Ognibene FP, Shelhamer JH, Hoffman GS, et al. Pneumocystitis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. Am J Respir Crit Care Med. 1995;151:795–799
  60. Onal S, Kazokoglu H, Koc A, et al. Rixumab for remission induction in a patient with relapsing necrotizing scleritis associated with limited Wegener's granulomatosis. Ocul Immunol Inflamm. 2008;16:230–232
  61. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359:2790–2803
  62. Pakrou N, Selva D, Leibovitch I. Wegener's granulomatosis: ophthalmic manifestations and management. Semin Arthritis Rheum. 2006;35:284–292
  63. Paul B, McElvanney AM, Agarwal S, et al. Two rare causes of posterior ischaemic optic neuropathy: eosinophilic fascitis and Wegener's granulomatosis. Br J Ophthalmol. 2002;86:1066–1068
  64. Pecorella I, La Cava M, Mannino G, et al. Diffuse granulomatous necrotizing scleritis. Acta Ophthalmol Scand. 2006;84:263–265
  65. Provenzale JM, Mukherji S, Allen NB, et al. Orbital involvement by Wegener's granulomatosis: imaging findings. AJR Am J Roentgenol. 1996;166:929–934
  66. Reynolds I, Tullo AB, John SL, et al. Corneal epithelial-specific cytokeratin 3 is an autoantigen in Wegener's granulomatosis-associated peripheral ulcerative keratitis. Invest Ophthalmol Vis Sci. 1999;40:2147–2151
  67. Robinson MR, Lee SS, Sneller MC, et al. Tarsal-conjunctival disease associated with Wegener's granulomatosis. Ophthalmology. 2003;110:1770–1780
  68. Samuelson TW, Margo CE. Protracted uveitis as the initial manifestation of Wegener's granulomatosis. Arch Ophthalmol. 1990;108:478–479
  69. Sandusky H, Cilluffo M, Braun J, et al. Ocular pANCA antigens are expressed in nonpigmented ciliary body epithelium and are conserved in multiple mammalian species. Ocul Immunol Inflamm. 2001;9:25–34
  70. Seo P, Specks U, Keogh KA. Efficacy of rituxmib in limited Wegener's granulomatosis with refractory granulomatous manifestations. J Rheumatol. 2008;35:2017–2023
  71. Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1. Ophthalmology. 2004;111:997–1008
  72. Skalka HW, Prchal JT. Effect of glucocorticoids on cataract formation. Arch Ophthalmol. 1980;98:1773–1777
  73. Specks U, Fervenza FC, McDonald TJ, et al. Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum. 2001;44:2836–2840
  74. Stegeman CA, Tervaert JW, de Jong PE, et al. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch co-trimoxazole study group. N Engl J Med. 1996;335:16–20
  75. Stegeman CA, Tervaert JW, Sluiter WJ, et al. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. 1994;120:12–17
  76. Stempel D, Sandusky H, Lampi K, et al. BetaB1-crystallin: identification of a candidate ciliary body uveitis antigen. Invest Ophthalmol Vis Sci. 2003;44:203–209
  77. Stone JH. Vasculitis: a collection of pearls and myths. Rheum Dis Clin North Am. 2007;33:691–739
  78. Stone JH, Holbrook JT, Marriott MA, et al. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum. 2006;54:1608–1618
  79. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363:221–232
  80. Talar-Williams C, Sneller MC, Langford CA, et al. Orbital socket contracture: a complication of inflammatory orbital disease in patients with Wegener's granulomatosis. Br J Ophthalmol. 2005;89:493–497
  81. Tanihara H, Nakayama Y, Honda Y. Wegener's granulomatosis with rapidly progressive retinitis and anterior uveitis. Acta Ophthalmol (Copenh). 1993;71:853–855
  82. Tullo AB, Durrington P, Graham E, et al. Florid xanthelasmata (yellow lids) in orbital Wegener's granulomatosis. Br J Ophthalmol. 1995;79:453–456
  83. Vandergheynst F, Van Gansbeke D, Cogan E. Wegener's granulomatosis masquerading as a renal cancer: a case report and review of the literature. Clin Exp Rheumatol. 2006;24:584–586
  84. Venkatesh P, Chawla R, Tewari HK. Hemiretinal vein occlusion in Wegener's granulomatosis. Eur J Ophthalmol. 2003;13:722–725
  85. Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, et al. Erdheim-Chester disease: Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore). 1996;75:157–169
  86. Villa-Forte A, Clark TM, Gomes M, et al. Substitution of methotrexate for cyclophosphamide in Wegener's granulomatosis. A 12-year single-practice experience. Medicine (Baltimore). 2007;86:269–277
  87. Vogiatzis KV. Bilateral blindness due to necrotizing scleritis in a case of Wegener's granulomatosis. Ann Ophthalmol. 1983;15:185–188
  88. Wang M, Khurana RN, Sadda SR. Central retinal vein occlusion in Wegener's granulomatosis without retinal vasculitis. Br J Ophthalmol. 2006;90:1435–1436
  89. Wegener's granulomatosis etanercept trial (WGET) research group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005;352:351–361
  90. WGET Research Group. Design of the Wegener's Granulomatosis Etanercept Trial (WGET). Control Clin Trials. 2002;23:450–468
  91. Woo TL, Francis IC, Wilcsek GA, et al. Australasian orbital and adnexal Wegener's granulomatosis. Ophthalmology. 2001;108:1535–1543

 Publication of this article is supported by an unrestricted grant from Research to Prevent Blindness. New York, NY.

PII: S0039-6257(09)00314-2

doi: 10.1016/j.survophthal.2009.12.003

Survey of Ophthalmology
Volume 55, Issue 5 , Pages 429-444 , September 2010