The authors have no relevant finan- crescentic glomerulonephritis. The myeloperoxidase and proteinase 3 cial interest in this article. sensitivity and specificity of both antibodies were positive concur- Corresponding author: Panagiotis tests are high for a vasculitic pro- rently. Magnetic resonance imag- Karadimas, MD, Medical Retina Unit, cess frequently associated with a sys- ing of the orbits showed enlarged ex- First Department of Ophthalmology, temic disease that requires prompt traocular muscles, and renal biopsy Henry Dunant Hospital, 107 Meso- immunosuppressive therapy.1,2 results showed florid necrotizing glo- gion Ave, 11526 Athens, Greece (e-mail: We report 4 cases of p-ANCA merulonephritis. After treatment [email protected]). positivity showing a spectrum of se- with high-dose steroids and azathio- vere ocular involvement. Two pa- prine sodium, the patient’s signs re- 1. Bouzas EA, Scott MH, Mastorakos G, Chrousos tients had been systemically un- solved dramatically, leaving some re- GP, Kaiser-Kupfer MI. Central serous chorio- well previously, but it was the ocular sidual diplopia controlled by prisms. retinopathy in endogenous hypercortisolism. Arch Ophthalmol. 1993;111:1229-1233. disease that prompted ANCA mea- Case 3. A 67-year-old man with 2. Bouzas EA, Karadimas P, Pournaras CJ. Cen- surement. ulcerative colitis and a previous right tral serous chorioretinopathy and glucocorti- serous retinal detachment had coids. Surv Ophthalmol. 2002;47:431-448. 3. Aalto-Korte K, Turpeinen M. Pharmacokinet- Report of Cases. Case 1. A 76-year- deteriorating vision in the left eye. ics of topical hydrocortisone at plasma level af- old man had a 12-month history of Visual acuities were hand move- ter applications once or twice daily in patients with widespread dermatitis. Br J Dermatol. 1995; red smarting eyes. Examination re- ments OD and 20/200 OS. Exami- 133:259-263. vealed bilateral peripheral ulcer- nation showed marked retinal pig- 4. Cook LJ, Freinkel RK, Zugerman C, Levin DL, ative keratitis with normal visual acu- ment epithelial mottling and macular Radtke R. Iatrogenic hyperadrenocorticism dur- ing topical steroid therapy: assessment of sys- ity and no proptosis. Investigations edema in both eyes and serous reti- temic effects by metabolic criteria. J Am Acad revealed chronic renal failure and nal detachment in the left eye. Re- Dermatol. 1982;6:1054-1060. positive levels of p-ANCA (1/160) but sults of fluorescein angiography and 5. Garden JM, Freinkel RK. Systemic absorption of topical steroids: metabolic effects as an index of not c-ANCA. Systemic treatment with B-scan ultrasonography were used mild hypercortisolism. Arch Dermatol. 1986; immunosuppressants was com- to confirm posterior scleritis. After 122:1007-1010. menced. Despite treatment, the kera- therapy with immunosuppres- topathy progressed, and p-ANCA lev- sants, the patient’s visual acuity im- els remained high. The patient then proved to 20/20 OS. Two years later, Ocular Involvement stopped treatment and developed vas- a relapse occurred, and p-ANCA in Systemic Vasculitis culitic anterior ischemic optic neu- findings were positive. His titre sub- Associated With ropathy in the right eye, with a vi- sequently normalized with treat- Perinuclear Antineutrophil sual acuity of 20/200 OD. ment, although his vision contin- Cytoplasmic Antibodies Case2.A37-year-oldwomanhad ued to deteriorate. an 8-week history of painless, swol- Case 4. A 58-year-old man had Antineutrophil cytoplasmic anti- len eyelids, variable diplopia, and in- a 15-month history of progressive body (ANCA) formation to myeloper- termittent arthralgia for the past year. left-sided headache, poor appetite, oxidase or perinuclear (p-ANCA) is Examination revealed impaired eleva- weight loss, and deafness. Cranial infrequent in ocular disease and is tion of both eyes, periorbital edema, nerve examination revealed left tri- reported in approximately 10% of and erythema (Figure 1) but no geminal nerve involvement and sen- patients with Wegener granuloma- visual changes, proptosis, or scleral sorineural deafness. Visual acuity tosis 1,2 as opposed to cytoplasmic injection. was normal. Fundoscopy demon- (c-ANCA) positivity (antibodies to Investigations revealed an in- strated a swollen right optic disc and proteinase 3), which is well recog- creased erythrocyte sedimentation bilateral white, elevated retinal pig- nized. Higher levels of p-ANCA are rate (107 mm/h) and C-reactive pro- ment epithelial lesions (Figure 2). also identified in microscopic poly- tein level (14.8 mg/L). Urinalysis re- These lesions showed early hypo- angiitis, Churg-Strauss syndrome, sults showed proteinuria and re- inflammatory bowel disease, and duced creatinine clearance. Both

Figure 2. Fundus photograph of the right eye showing a swollen optic disc and creamy white, Figure 1. Photograph showing right convergent squint, periorbital edema, and eyelid erythema but no elevated lesions at the level of the retinal pigment proptosis in case 2. epithelium at the posterior pole in case 4.

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 fluorescence and late hyperfluores- to serous retinal detachments. In a the eye manifestation, and in the cence at fluorescein angiography. study of patients with anterior uve- third case, if p-ANCA levels had Magnetic resonance imaging showed itis, p-ANCA was a susceptibility been tested previously, with appro- marked, diffuse enhancement of the marker for immune-mediated dis- priate therapy the patient may have pachymeninges, results of a lum- eases, including ulcerative colitis.3 avoided relapse. Positive p-ANCA bar puncture indicated central ner- In case 4, the patient had dif- findings highlight the need for re- vous system inflammation, and fuse inflammatory pachymeningitis ferral for a systemic workup and p-ANCA findings were positive with multiple cranial neuropathies prompt administration of immuno- (anti-myeloperoxidase 54%). and choroiditis similar to acute suppressive agents to reduce the risk Treatment with immunosup- multifocal placoid pigment epithe- of visual morbidity, organ damage, pressants resulted in a reduction in liopathy. As far as we are aware, no and even death. p-ANCA titre with dramatic improve- case of increased p-ANCA levels ment of symptoms. Despite 1 recur- and acute multifocal placoid pig- Samantha S. Dandekar, MRCOphth rence of headache associated with an ment epitheliopathy has previously Niro N. Narendran, MRCOphth increase in p-ANCA levels, 5 years been reported. Beth Edmunds, FRCOphth, MD later the patient’s disease remained Other reports of p-ANCA in as- Elizabeth M.Graham,FRCP,FRCOphth well controlled with oral steroids. sociation with central nervous sys- London, England tem and ocular disease include a case Comment. These 4 cases demon- of Wegener granulomatosis with The authors have no relevant finan- strate the diversity and aggressive- pachymeningitis, multiple cranial cial interest in this article. ness of eye disease associated with neuropathies, and central retinal ar- 4 Corresponding author and systemic vasculitis characterzied by tery occlusion and 1 of pseudo– reprints: Samantha S. Dandekar, increased p-ANCA levels. Two pa- Foster Kennedy syndrome with 5 MRCOphth, Department of Clinical tients probably have Wegener granu- pachymeningitis. Prompt systemic Ophthalmology, Professional Unit, lomatosis, 1 with chronic renal fail- treatment in both cases resulted in a Moorfield’s Eye Hospital, City Road, ure, keratomalacia, and vasculitic favorable systemic response, al- London EC1V 2PD, England (e-mail: anterior ischemic optic neuropathy though vision did not improve. [email protected]). and the other with necrotizing glo- In all cases, p-ANCA testing merulonephritis, enlarged orbital was repeated to confirm positivity, 1. Kaufman AH, Niles JL, Foster CS. ANCA test in muscles, and periorbital inflamma- and serial measurements showed a ophthalmic inflammatory disease. Int Ophthal- tion. The presence of p-ANCA in reduction in titre with treatment in mol Clin. 1994;34:215-227. 2. Soukiasian SH, Foster CS, Niles JL, Raizman MB. conjunction with the clinical signs 2 cases. Results of other studies have Diagnostic value of anti-neutrophil cytoplas- and chronic renal failure led to the also shown correlation with dis- mic antibodies in scleritis associated with We- diagnosis of systemic vasculitis and ease activity.2 gener’s granulomatosis. Ophthalmology. 1992; 99:125-132. probably Wegener granulomatosis. This series highlights the im- 3. Gordon LK, Eggena M, Holland GN, Weisz JM, In the latter case, both c-ANCA and portance of p-ANCA in addition to Braun J. pANCA antibodies in patients with an- p-ANCA findings were positive. In- c-ANCA in the diagnosis of often ag- terior uveitis: identification of a marker anti- body usually associated with ulcerative colitis. terestingly, neither patient showed gressive ocular disease that involves J Clin Immunol. 1998;18:264-271. evidence of proptosis, and the lat- the sclera, orbit, and posterior cili- 4. Nagashima T, Maguchi S, Terayama Y, et al. P-ANCA-positive Wegener’s granulomatosis pre- ter had no scleritis or pain. ary circulation associated with sys- sentingwithhypertrophicpachymeningitisandmul- In case 3, the patient had ul- temic vasculitis and that all require tiple cranial neuropathies: case report and review cerative colitis, one of the rarer as- immunosuppressive treatment.1 of literature. Neuropathology. 2000;20:23-30. 5. Tamai H, Tamai K, Yuasa H. Pachymenigitis with sociations of p-ANCA, and devel- In 2 cases, no other systemic pseudo-Foster Kennedy syndrome. Am J Oph- oped posterior scleritis progressing involvement was evident until after thalmol. 2000;130:535-537.

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