Ocular Involvement in Systemic Vasculitis Associated With PerinuclearAntineutrophil Cytoplasmic Antibodies | Rheumatology | JAMA Ophthalmology | JAMA Network
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Clinicopathologic Reports, Case Reports, and Small Case Series
May 2004

Ocular Involvement in Systemic Vasculitis Associated With PerinuclearAntineutrophil Cytoplasmic Antibodies

Author Affiliations

W. RichardGreenMD

Arch Ophthalmol. 2004;122(5):786-787. doi:10.1001/archopht.122.5.786

Antineutrophil cytoplasmic antibody (ANCA) formation to myeloperoxidaseor perinuclear (p-ANCA) is infrequent in ocular disease and is reported inapproximately 10% of patients with Wegener granulomatosis 1,2 asopposed to cytoplasmic (c-ANCA) positivity (antibodies to proteinase 3), whichis well recognized. Higher levels of p-ANCA are also identified in microscopicpolyangiitis, Churg-Strauss syndrome, inflammatory bowel disease, and crescenticglomerulonephritis. The sensitivity and specificity of both tests are highfor a vasculitic process frequently associated with a systemic disease thatrequires prompt immunosuppressive therapy.1,2

We report 4 cases of p-ANCA positivity showing a spectrum of severeocular involvement. Two patients had been systemically unwell previously,but it was the ocular disease that prompted ANCA measurement.

Report of Cases.

Case 1. A 76-year-old man had a 12-month historyof red smarting eyes. Examination revealed bilateral peripheral ulcerativekeratitis with normal visual acuity and no proptosis. Investigations revealedchronic renal failure and positive levels of p-ANCA (1/160) but not c-ANCA.Systemic treatment with immunosuppressants was commenced. Despite treatment,the keratopathy progressed, and p-ANCA levels remained high. The patient thenstopped treatment and developed vasculitic anterior ischemic optic neuropathyin the right eye, with a visual acuity of 20/200 OD.

Case 2. A 37-year-old woman had an 8-week history of painless, swollen eyelids,variable diplopia, and intermittent arthralgia for the past year. Examinationrevealed impaired elevation of both eyes, periorbital edema, and erythema(Figure 1) but no visual changes,proptosis, or scleral injection.

Figure 1. 
Photograph showing right convergentsquint, periorbital edema, and eyelid erythema but no proptosis in case 2.

Photograph showing right convergentsquint, periorbital edema, and eyelid erythema but no proptosis in case 2.

Investigations revealed an increased erythrocyte sedimentation rate(107 mm/h) and C-reactive protein level (14.8 mg/L). Urinalysis results showedproteinuria and reduced creatinine clearance. Both myeloperoxidase and proteinase3 antibodies were positive concurrently. Magnetic resonance imaging of theorbits showed enlarged extraocular muscles, and renal biopsy results showedflorid necrotizing glomerulonephritis. After treatment with high-dose steroidsand azathioprine sodium, the patient's signs resolved dramatically, leavingsome residual diplopia controlled by prisms.

Case 3. A 67-year-old man with ulcerative colitis and a previous right serousretinal detachment had deteriorating vision in the left eye. Visual acuitieswere hand movements OD and 20/200 OS. Examination showed marked retinal pigmentepithelial mottling and macular edema in both eyes and serous retinal detachmentin the left eye. Results of fluorescein angiography and B-scan ultrasonographywere used to confirm posterior scleritis. After therapy with immunosuppressants,the patient's visual acuity improved to 20/20 OS. Two years later, a relapseoccurred, and p-ANCA findings were positive. His titre subsequently normalizedwith treatment, although his vision continued to deteriorate.

Case 4. A 58-year-old man had a 15-month history of progressive left-sided headache,poor appetite, weight loss, and deafness. Cranial nerve examination revealedleft trigeminal nerve involvement and sensorineural deafness. Visual acuitywas normal. Fundoscopy demonstrated a swollen right optic disc and bilateralwhite, elevated retinal pigment epithelial lesions (Figure 2). These lesions showed early hypofluorescence and latehyperfluorescence at fluorescein angiography. Magnetic resonance imaging showedmarked, diffuse enhancement of the pachymeninges, results of a lumbar punctureindicated central nervous system inflammation, and p-ANCA findings were positive(anti-myeloperoxidase 54%).

Figure 2. 
Fundus photograph of the righteye showing a swollen optic disc and creamy white, elevated lesions at thelevel of the retinal pigment epithelium at the posterior pole in case 4.

Fundus photograph of the righteye showing a swollen optic disc and creamy white, elevated lesions at thelevel of the retinal pigment epithelium at the posterior pole in case 4.

Treatment with immunosuppressants resulted in a reduction in p-ANCAtitre with dramatic improvement of symptoms. Despite 1 recurrence of headacheassociated with an increase in p-ANCA levels, 5 years later the patient'sdisease remained well controlled with oral steroids.


These 4 cases demonstrate the diversity and aggressiveness of eye diseaseassociated with systemic vasculitis characterized by increased p-ANCA levels.Two patients probably have Wegener granulomatosis, 1 with chronic renal failure,keratomalacia, and vasculitic anterior ischemic optic neuropathy and the otherwith necrotizing glomerulonephritis, enlarged orbital muscles, and periorbitalinflammation. The presence of p-ANCA in conjunction with the clinical signsand chronic renal failure led to the diagnosis of systemic vasculitis andprobably Wegener granulomatosis. In the latter case, both c-ANCA and p-ANCAfindings were positive. Interestingly, neither patient showed evidence ofproptosis, and the latter had no scleritis or pain.

In case 3, the patient had ulcerative colitis, one of the rarer associationsof p-ANCA, and developed posterior scleritis progressing to serous retinaldetachments. In a study of patients with anterior uveitis, p-ANCA was a susceptibilitymarker for immune-mediated diseases, including ulcerative colitis.3

In case 4, the patient had diffuse inflammatory pachymeningitis withmultiple cranial neuropathies and choroiditis similar to acute multifocalplacoid pigment epitheliopathy. As far as we are aware, no case of increasedp-ANCA levels and acute multifocal placoid pigment epitheliopathy has previouslybeen reported.

Other reports of p-ANCA in association with central nervous system andocular disease include a case of Wegener granulomatosis with pachymeningitis,multiple cranial neuropathies, and central retinal artery occlusion 4 and 1 of pseudo–Foster Kennedy syndrome withpachymeningitis.5 Prompt systemic treatmentin both cases resulted in a favorable systemic response, although vision didnot improve.

In all cases, p-ANCA testing was repeated to confirm positivity, andserial measurements showed a reduction in titre with treatment in 2 cases.Results of other studies have also shown correlation with disease activity.2

This series highlights the importance of p-ANCA in addition to c-ANCAin the diagnosis of often aggressive ocular disease that involves the sclera,orbit, and posterior ciliary circulation associated with systemic vasculitisand that all require immunosuppressive treatment.1

In 2 cases, no other systemic involvement was evident until after theeye manifestation, and in the third case, if p-ANCA levels had been testedpreviously, with appropriate therapy the patient may have avoided relapse.Positive p-ANCA findings highlight the need for referral for a systemic workupand prompt administration of immunosuppressive agents to reduce the risk ofvisual morbidity, organ damage, and even death.

Corresponding author and reprints: Samantha S. Dandekar, MRCOphth,Department of Clinical Ophthalmology, Professional Unit, Moorfield's Eye Hospital,City Road, London EC1V 2PD, England (e-mail: s.dandekar@ucl.ac.uk).

The authors have no relevant financial interest in this article.

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