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Arch Ophthalmol. 2004;122:786-787.

Antineutrophil cytoplasmic antibody (ANCA) formation to myeloperoxidase or perinuclear (p-ANCA) is infrequent in ocular disease and is reported in approximately 10% of patients with Wegener granulomatosis ^1-2 as opposed to cytoplasmic (c-ANCA) positivity (antibodies to proteinase 3), which is well recognized. Higher levels of p-ANCA are also identified in microscopic polyangiitis, Churg-Strauss syndrome, inflammatory bowel disease, and crescentic glomerulonephritis. The sensitivity and specificity of both tests are high for a vasculitic process frequently associated with a systemic disease that requires prompt immunosuppressive therapy.^1-2

We report 4 cases of p-ANCA positivity showing a spectrum of severe ocular 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 history of red smarting eyes. Examination revealed bilateral peripheral ulcerative keratitis with normal visual acuity and no proptosis. Investigations revealed chronic 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 then stopped treatment and developed vasculitic anterior ischemic optic neuropathy in 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. Examination revealed impaired elevation of both eyes, periorbital edema, and erythema (Figure 1) but no visual changes, proptosis, or scleral injection.

View larger version (82K): [in this window] [in a new window] Figure 1. Photograph showing right convergent squint, 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 showed proteinuria and reduced creatinine clearance. Both myeloperoxidase and proteinase 3 antibodies were positive concurrently. Magnetic resonance imaging of the orbits showed enlarged extraocular muscles, and renal biopsy results showed florid necrotizing glomerulonephritis. After treatment with high-dose steroids and azathioprine sodium, the patient's signs resolved dramatically, leaving some residual diplopia controlled by prisms.

Case 3. A 67-year-old man with ulcerative colitis and a previous right serous retinal detachment had deteriorating vision in the left eye. Visual acuities were hand movements OD and 20/200 OS. Examination showed marked retinal pigment epithelial mottling and macular edema in both eyes and serous retinal detachment in the left eye. Results of fluorescein angiography and B-scan ultrasonography were used to confirm posterior scleritis. After therapy with immunosuppressants, the patient's visual acuity improved to 20/20 OS. Two years later, a relapse occurred, and p-ANCA findings were positive. His titre subsequently normalized with 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 revealed left trigeminal nerve involvement and sensorineural deafness. Visual acuity was normal. Fundoscopy demonstrated a swollen right optic disc and bilateral white, elevated retinal pigment epithelial lesions (Figure 2). These lesions showed early hypofluorescence and late hyperfluorescence at fluorescein angiography. Magnetic resonance imaging showed marked, diffuse enhancement of the pachymeninges, results of a lumbar puncture indicated central nervous system inflammation, and p-ANCA findings were positive (anti-myeloperoxidase 54%).

View larger version (66K): [in this window] [in a new window] Figure 2. Fundus photograph of the right eye showing a swollen optic disc and creamy white, elevated lesions at the level of the retinal pigment epithelium at the posterior pole in case 4.

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

Comment.
These 4 cases demonstrate the diversity and aggressiveness of eye disease associated 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 other with necrotizing glomerulonephritis, enlarged orbital muscles, and periorbital inflammation. The presence of p-ANCA in conjunction with the clinical signs and chronic renal failure led to the diagnosis of systemic vasculitis and probably Wegener granulomatosis. In the latter case, both c-ANCA and p-ANCA findings were positive. Interestingly, neither patient showed evidence of proptosis, and the latter had no scleritis or pain.

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

In case 4, the patient had diffuse inflammatory pachymeningitis with multiple cranial neuropathies and choroiditis similar to acute multifocal placoid pigment epitheliopathy. As far as we are aware, no case of increased p-ANCA levels and acute multifocal placoid pigment epitheliopathy has previously been reported.

Other reports of p-ANCA in association with central nervous system and ocular 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 with pachymeningitis.⁵ Prompt systemic treatment in both cases resulted in a favorable systemic response, although vision did not improve.

In all cases, p-ANCA testing was repeated to confirm positivity, and serial 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-ANCA in the diagnosis of often aggressive ocular disease that involves the sclera, orbit, and posterior ciliary circulation associated with systemic vasculitis and that all require immunosuppressive treatment.¹

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

The authors have no relevant financial interest in this article.

AUTHOR INFORMATION

Samantha S. Dandekar, MRCOphth; Niro N. Narendran, MRCOphth; Beth Edmunds, FRCOphth, MD; Elizabeth M. Graham, FRCP, FRCOphth
London, England

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{at}ucl.ac.uk).

REFERENCES
1. Kaufman AH, Niles JL, Foster CS. ANCA test in ophthalmic inflammatory disease. Int Ophthalmol Clin. 1994;34:215-227. ISI | PUBMED 2. Soukiasian SH, Foster CS, Niles JL, Raizman MB. Diagnostic value of anti-neutrophil cytoplasmic antibodies in scleritis associated with Wegener's granulomatosis. Ophthalmology. 1992;99:125-132. ISI | PUBMED 3. Gordon LK, Eggena M, Holland GN, Weisz JM, Braun J. pANCA antibodies in patients with anterior uveitis: identification of a marker antibody usually associated with ulcerative colitis. J Clin Immunol. 1998;18:264-271. FULL TEXT | ISI | PUBMED 4. Nagashima T, Maguchi S, Terayama Y, et al. P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature. Neuropathology. 2000;20:23-30. PUBMED 5. Tamai H, Tamai K, Yuasa H. Pachymenigitis with pseudo-Foster Kennedy syndrome. Am J Ophthalmol. 2000;130:535-537. PUBMED

SECTION EDITOR: W. Richard Green, MD

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ABSTRACT | FULL TEXT