Elsevier

Survey of Ophthalmology

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

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

https://doi.org/10.1016/j.survophthal.2009.12.003Get rights and content

Abstract

Wegener's granulomatosis (WG) is a systemic inflammatory disease whose histopathologic features often include necrosis, granuloma formation, and vasculitis of small-to-medium-sized vessels. WG involves many interrelated pathogenic pathways that are genetic, cell-mediated, neutrophil-mediated, humoral, and environmental. WG most commonly involves the upper respiratory tract, lungs, and kidneys, but has been reported to affect almost any organ. Ophthalmologic involvement is an important cause of morbidity in WG patients, occurring in approximately one-half of patients. The presence of unexplained orbital inflammatory disease, scleritis, peripheral ulcerative keratitis, cicatricial conjunctivitis, nasolacrimal duct stenosis, retinal vascular occlusion, or infrequently uveitis should raise the question of possible WG. A thorough clinical examination, laboratory testing, radiologic imaging, and histologic examination are essential to diagnosing WG and excluding potential mimics. Previously a uniformly fatal disease, treatment with cytotoxic and immunosuppressive agents has greatly improved survival. Treatment-related morbidity is a serious limitation of conventional therapies, leading to numerous ongoing studies of alternative agents.

Introduction

Wegener's granulomatosis (WG) is a systemic inflammatory disease whose histopathologic features often include necrosis, granuloma formation, and vasculitis of small-to-medium-sized vessels. Antibodies to neutrophil cytoplasmic antigens (ANCA) are present in about 80–90% of patients and appear to play a role in pathogenesis, but are not likely to be essential to cause disease. WG can affect any organ system, but classically affects the upper and lower respiratory tracts and, in most cases, the kidney. Once a rapidly fatal disease, WG can now be controlled with glucocorticoid and other immunosuppressive therapies.27

Ophthalmologic involvement is an important cause of morbidity, occurring in approximately 50% of WG patients. Although orbital disease is the most common ocular manifestation, WG may involve almost any eye structure.

Section snippets

Epidemiology

The annual incidence of WG in the United States is 3 per 100,000. There are about 2,300 newly diagnosed cases in the United States per year. The average age at the time of diagnosis is about 40–55 years, with no significant sex bias. WG is most common in whaite patients. African Americans are relatively under-represented, constituting about 2–8% of most studies, although making up 11–14% of the U.S. populations studied.27

Etiology and Pathogenesis

Bacteria and other infectious organisms have been implicated as triggers of autoimmune diseases, but none have been proven to play a definite etiologic role in WG. In support of a role for infection, Stegeman et al demonstrated that chronic nasal infestation by S. aureus in patients with WG was associated with a higher rate of relapse than patients without.74 This same group also reported a decrease in the rate of ear, nose, or throat (ENT) (but not renal or pulmonary) relapses in patients

Clinical Manifestations

WG most commonly involves the upper respiratory tract, lungs, and kidneys, but has been reported to affect almost any organ27 (Fig. 1, Table 1).

Differential Diagnosis

The diagnosis of WG should be suspected in any patients with upper or lower respiratory findings and evidence of glomerulonephritis. The American College of Rheumatology definition is the presence of two out of four of the 1990 criteria for WG, although more recent studies have included a positive ANCA immunoassay result45, 88 (Table 4).

Orbital disease in WG is often difficult to distinguish from other inflammatory conditions. The differential diagnosis of orbital inflammation is broad and

Treatment

Prior to 1970, WG was usually a fatal disease. Only 50% of patients survived 5 months, and mortality was about 80% within 1 year of diagnosis. With glucocorticoids alone, mean survival time was only 1 year. Currently, the combination of glucocorticoids with either cyclophosphamide or methotrexate or azathioprine can lead to disease remission and prolonged survival. WG is now a very treatable, albeit incurable, disease, with survival rates as high as 95% at 5-year follow-up and ∼80% after 10

Conclusion

WG is a systemic vasculitis that is almost always fatal if untreated. Ophthalmologic involvement is common and may be the initial presenting complaint. Ophthalmologists should have a high index of suspicion for WG in patients who present with unexplained IOI, scleritis, peripheral ulcerative keratitis, cicatricial conjunctivitis, nasolacrimal duct stenosis, or retinal vascular occlusion. Inquiries about the presence of other systemic symptoms, particularly sinonasal disease, hematuria,

Method of Literature Search

Pubmed was queried with combinations not limited to the following search terms: Wegener's granulomatosis and eye, orbit, orbital inflammation, conjunctiva, conjunctivitis, sclera, scleritis, uveitis, retina, retinitis, retinal vasculitis, pathogenesis, epidemiology. A review of the search results was performed and relevant articles to the topics of clinical manifestations, differential diagnosis, and treatment were included. Relevant articles to the conditions considered in the differential

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

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