Granulomatosis With Polyangiitis Presenting as Occlusive Retinal Vasculitis

Abstract

Purpose:

We discuss an unusual case of granulomatosis with polyangiitis (GPA) presenting as anterior uveitis with occlusive retinal vasculitis.

Methods:

A case report is presented.

Results:

A 60-year-old woman with a history of autoimmune disease presented to the retina clinic with red eyes and blurry vision in both eyes. An examination showed anterior uveitis with retinal vasculitis, and topical steroids were started in both eyes. One month later, the patient’s vision worsened and an optical coherence tomography scan showed new central cystoid macular edema in the left eye. An antivascular endothelial growth factor injection was given. The next day, her vision was “black” in the left eye and a fundus examination showed global ischemia. A comprehensive uveitis workup was positive for cytoplasmic-staining antineutrophilic cytoplasmic antibody. A diagnosis of GPA was confirmed with a renal biopsy.

Conclusions:

Physician awareness of ocular GPA presentation is vital, and GPA management is most successful with a multidisciplinary team.

Introduction

Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a rare multisystem autoimmune disease defined by necrotizing granulomatous vasculitis involving small-sized and medium-sized blood vessels. ¹ GPA can be triggered by an infectious or environmental agent in patients with genetic susceptibility. GPA most commonly affects the nasopharynx, lungs, and kidneys, although ocular manifestations are seen in about 50% of cases. Ocular symptoms are the first signs of GPA in only about 15% of cases. ² Occlusive retinal vasculitis has been reported in less than 5% of cases of GPA. ³ Here, we report an unusual presentation of GPA manifesting initially as anterior uveitis with progressive occlusive retinal vasculitis.

Methods

Case Report

A 60-year-old woman with a 3-week history of bilateral red eyes and blurry vision was referred to the retina clinic for examination. Her medical history included asthma, psoriasis, sinusitis, arthritis, hypothyroidism, and hypertension. Six months previously she experienced an episode of viral pericarditis that resolved spontaneously.

On assessment, her visual acuity was 20/20 in both eyes. A slitlamp examination showed 2+ cells in the anterior chamber bilaterally. Fluorescein angiograms showed temporal vascular remodeling and arteriovenous fistulas in her right eye (Figure 1A) and temporal vascular remodeling with mild optic nerve leakage in her left eye (Figure 1B). No obvious retinal abnormalities were seen on optical coherence tomography (OCT).

Figure 1.

Late-phase fluorescein angiograms of the (A) right eye and (B) left eye show arteriovenous fistulas and optic nerve leakage, respectively, and temporal vascular remodeling bilaterally.

Based on her symptoms and the evidence of vascular involvement, a diagnosis of anterior uveitis with vasculitis was made. QuantiFERON-TB Gold, HLA B27, Lyme antibodies, chest x-ray, and angiotensin-converting enzyme levels were all normal. An atinuclear antibody test was positive (1:80 titer with nuclear, dense, fine-speckled pattern), and the white blood cell count was elevated with neutrophilic predominance. The positive antinuclear antibodies in the context of autoimmune history raised concern of retinal vascular involvement secondary to systemic disease. Topical steroids were started with a slow taper, and the patient reported improvement in her symptoms.

One month later, the patient suddenly woke up with worsening vision in her left eye. She could only count fingers with her left eye. On examination of her left fundus, optic nerve edema and hemorrhages were noted. OCT of her left eye showed new cystoid macular edema (Figure 2). Her right eye did not have any changes.

Figure 2.

Optical coherence tomography scan of the left eye shows new central cystoid macular edema.

The patient’s presentation of vision loss, macular edema, and hemorrhages was suspicious for an evolving early central retinal vein occlusion. While we were concerned about an underlying inflammatory cause for the patient’s symptoms, an antivascular endothelial growth factor injection (bevacizumab) was administered to treat the acute macular edema in her left eye.

The next day, the patient reported “black” vision in her left eye. Fundus photographs showed hemorrhages, vascular sheathing, and global ischemia in her left eye (Figure 3A). Fundus autofluorescence highlighted these hemorrhages (Figure 3B). OCT of her left eye revealed retinal thickening, central subretinal fluid, vitreous cells, and optic nerve swelling. Her right eye remained stable.

Figure 3.

(A) Fundus photograph of the patient’s left eye shows hemorrhages globally and optic nerve swelling. (B) Fundus autofluorescence highlights hemorrhages in the left eye.

A diagnosis of occlusive retinal vasculitis in her left eye was made, and a more comprehensive uveitis workup was initiated. Her laboratory values were positive for cytoplasmic-staining antineutrophilic cytoplasmic antibody (c-ANCA), concerning for GPA. The patient was started on azathioprine, rituximab, and oral prednisone and was referred to a rheumatologist, who recommended a renal biopsy. A biopsy revealed negatively immunofluorescent pauci-immune crescentic glomerulonephritis, characteristic of GPA, thus confirming her diagnosis (Figure 4).

Figure 4.

Renal biopsy with a methenamine silver-periodic acid–Schiff stain at 400× magnification shows affected and unaffected glomeruli. The glomerulus on the lower right is involved by a large cellular crescent. The glomerulus without crescents (left) is normocellular. Given the negative immunofluorescence, the constellation of findings is consistent with pauci-immune crescentic glomerulonephritis, which is typical of renal involvement by granulomatosis with polyangiitis.

Results

GPA is a rare, rapidly progressive autoimmune disease characterized by granulomatous necrotizing vasculitis of small-sized and medium-sized blood vessels. ¹ The prevalence of GPA in the United States is approximately 3 cases per 100 000 people. ³ About 80% to 95% of systemic cases of GPA are positive for c-ANCA. The pathophysiology of the disease might be related to ANCA-driven neutrophil degranulation, leading to vasculitis in multiple organ systems. ¹

Occlusive retinal vasculitis resulting from GPA is seen in only about 5% of cases. ³ Occlusive retinal vasculitis is a sight-threatening inflammation of the retinal vessels that might present with symptoms of blurry vision, floaters, scotomas, or metamorphopsia. On examination, it can manifest as perivascular sheathing or cuffing, vascular leakage, vascular occlusion, cotton-wool spots, or hemorrhages. In the context of a patient presenting with vasculitis with a history of autoimmune disease, GPA should be considered.

Treatment of GPA consists of oral glucocorticoids with cyclophosphamide, methotrexate, or azathioprine. Ocular manifestations of GPA might require topical or intravenous glucocorticoids. Rituximab has also been shown to be effective in treating ocular manifestations. ²

Conclusions

Although GPA rarely presents with ocular symptoms as the first signs of disease, physician awareness of this presentation is vital to decrease morbidity and mortality. The management and treatment of GPA is most successful with a multidisciplinary team, including ophthalmologists, rheumatologists, nephrologists, and surgeons when needed.