Grand Round Case www.jpgmonline.com Unilateral central retinal artery occlusion followed by contralateral anterior ischaemic optic neuropathy

Khosla P, Gogia A, Agarwal PK, Jain KP

Department of Medicine, 65-year-old lady with long-standing hypertension, presented with history of headache and Sir Ganga Ram Hospital, A odynophagia for 2 ½ months, sudden painless loss of vision of right eye for 20 days prior to Rajinder Nagar, New admission and blurring of vision in the left eye. She also had multiple episodes of amaurosis fugax Delhi - 110 060. India. for 2 days. Permanent visual loss in the right eye followed an episode of amaurosis fugax. There was history of anorexia and weight loss. There was no history of diabetes mellitus, tuberculosis and the Correspondence: patient’s father and brother had similar complaints but their detailed records were not available. Atul Gogia, E-mail: [email protected] On examination the elderly lady was conscious, oriented, of average build and nourishment. Her pulse rate was 86/min, BP was 130/80mmHg and the temperature was 37°C. She had pallor, oral thrush and palpable, thickened and tender superficial temporal arteries (the right being thicker than the left). On examination the right fundus showed a cherry red spot at the macula suggestive of central retinal artery occlusion while left fundoscopy showed pallid disc oedema with peridiscal

Received : 30-04-04 haemorrhage suggestive of anterior ischaemic optic neuropathy (AION). Review completed : 09-06-04 Accepted : 08-07-04 What is the possible aetiological diagnosis in this patient at this stage? PubMed ID : 15377812 Given the history of hypertension, headache, multiple episodes of amaurosis fugax, fundal changes J Postgrad Med 2004;50:219-21 consistent with central retinal artery occlusion (CRAO) in the right eye and with AION in the left

eye, possible differential diagnoses include arteritic and non- ESR 110 mm at the end of 1 hr and thrombocytosis (platelets arteritic conditions involving the retinal blood vessels.1 The 6,20,000/cumm). p-ANCA, c-ANCA and ANA were negative. non-arteritic causes include emboli composed of either cho- CT scan of the brain showed a well-defined meningioma in lesterol, calcium or platelet fibrin debris. The most common relation to the right occipital bone under the tentorium. This source is an atherosclerotic plaque in the carotid artery, aorta was an incidental finding and was not contributing to her or heart. The important arteritic causes include giant cell ar- present problem. The liver and renal function tests were nor- teritis and various collagen vascular disorders like systemic lu- mal. Her coagulation and lipid profiles were also normal. Her pus erythematosus. fasting blood glucose was 98mg/dl. Chest radiograph and echocardiography did not reveal any abnormality. MRI angi- How would you investigate this patient to reach to a diagno- ography of the cranial vessels showed diffuse narrowing of the sis? blood vessels. The right temporal artery biopsy showed mixed The investigations to be done should include: cell inflammatory infiltrates associated with disruption of in- (i) To rule out the non-arteritic causes leading to the head- ternal elastic lamina and was suggestive of giant cell arteritis. ache and visual symptoms: Echocardiography, CT Scan of the head, Lipid and coagulation profile. What are the clinical manifestations of Giant Cell Arteritis? (ii) To look for possible arteritic aetiological causes: Chest Giant cell arteritis (GCA), a chronic vasculitis of large and X-ray, ANA, c-ANCA, p-ANCA, temporal artery biopsy medium-sized vessels, is a disease that primarily affects pa- once there is suspicion of Giant Cell Arteritis. tients over 50 years of age. It has been described in all races but is more common in whites. The onset of GCA tends to be What other investigations are required for the complete work- gradual, but can be abrupt in a minority of subjects.3 Systemic up of this patient? symptoms are present in about half of the patients. Headache Complete blood count, renal and liver function tests, estima- is probably the most frequent symptom and occurs in two- tion of blood glucose level and MRI angiography of the cranial thirds of patients2,3 and may be associated with tenderness over vessels. the temporal artery. Headache is frequently marked and tends to be located over the temporal or occipital areas. Nearly half The results of the investigations done revealed leucocytosis of the patients suffer from claudications of jaw muscles. Oc- (total leucocyte count 16500/cu mm, Neutrophils 89%, casionally, intermittent claudications may occur in the mus- Lymphocytes 10%, Monocytes 1%, Eosinophils 1%), elevated cles of the tongue or in those involved in swallowing.

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Khosla et al: Contralateral anterior ischemic optic neuropathy

Visual loss is the most dreaded complication of GCA and it uncommon for cases with GCA to have two different lesions usually results from AION or CRAO. Partial or complete loss in the same eye due to the involvement of the ophthalmic of vision in one or both eyes occurs in up to 20% of patients. artery in the arteritic process. Affected patients typically report partially obscured vision, which may progress to total blindness. If untreated, the other What are the various mechanisms of blindness in a case of eye is likely to become affected within one to two weeks. GCA? Amaurosis fugax is an important visual symptom that precedes Visual loss is the most dreaded complication of GCA and vari- permanent visual loss in 44% of patients.3 ous possible aetiologies include AION, CRAO and PION. The basic mechanism leading to visual loss in a case of GCA is What is the prognosis in this condition? arteritis. Visual loss in GCA is often irreversible even with appropriate treatment. The main factor influencing the therapeutic re- What is the gold standard for diagnosing Giant Cell Arteri- sponse is the delay in diagnosing the condition and instituting tis? appropriate therapy.5 In a retrospective study, 7 of 12 patients Temporal artery biopsy is recommended in all patients who treated within the first 24 hours after the onset of the visual are suspected of having Giant cell arteritis. The inflammatory loss showed improvement. But when the treatment was de- involvement of affected arteries is often intermittent rather layed for more than one day, only 1 of 17 patients had some than continuous. When possible, temporal artery biopsy should recovery of vision. Several case reports have suggested that be performed before treatment is initiated but treatment intravenous pulse steroid therapy may be the treatment of should not be delayed just to obtain a histopathological diag- choice for patients with recent visual loss due to GCA. Al- nosis. Examination of temporal artery biopsy specimens may though its efficacy seems to be comparable to that of high- reveal evidence of arteritis even after more than two weeks of dose oral prednisolone, immediate treatment is of great im- corticosteroid therapy.10 Concern about failing to establish the portance. diagnosis (histopathologically) because of previous treatment should never interfere with the institution of appropriate treat- What are the predictors of ischaemic manifestations of GCA? ment. Some investigators have tried to assess the best predictors of visual ischemic manifestations and permanent visual loss in In GCA, arteries are usually affected by an inflammatory infil- GCA.5,6 Anaemia was found to be a negative predictor for visual trate associated with marked disruption of internal elastic ischemic manifestations. In contrast, as described in the lamina. This infiltrate is usually focal and segmental. The clas- present case, amaurosis fugax was a predictor of irreversible sical histological picture of GCA, observed in 50% of the cases, visual loss.6 In approximately 10-15% patients, the branches of is of granulomatous inflammation in which giant cells are usu- the aortic arch, particularly the subclavian and axillary arteries ally located at the junction between the intima and media. become narrowed and result in the claudication of the arms. The other 50% have panarteritis with a mixed cell inflamma- Thoracic aortic aneurysm is 17 times as likely in patients with tory infiltrate that is predominantly composed of GCA in comparison to those without the disease.7 lymphomononucleated cells with occasional neutrophils and eosinophils but without giant cells. The American College of Rheumatology in 1990 (Table 1) for- mulated ARA Criteria for the classification of giant cell arteri- How would you manage this patient? tis.7,8 These criteria were designed for use in investigative stud- The patient was started on intravenous methylprednisolone 1 ies to help distinguish GCA from other types of vasculitides. gm for 5 days on high index of suspicion followed by oral pred- They are not useful for making the diagnosis in an individual nisolone at 1.5 mg/kg.Steroid therapy should be continued patient. initially for one month and then slowly tapered off to a main- tenance dose of 7.5 to 10 mg/day. The therapy should be con- Our patient had all the features of GCA. She had bilateral tinued for 1-2 years to prevent relapse. The side effects of ster- vision loss with two different eye lesions with progressive visual oids should be regularly monitored and patients who can tol- loss despite treatment with high-dose steroids. She had CRAO erate it may be started on alternate day regimen. The use of in the right eye with AION in the left eye, which is a distinctly steroid sparing agents like Methotrexate an other immuno- unusual occurrence; only two such cases have been reported suppressive agents still warrant large randomised control tri- in the literature.9 It may, however, be conceded that it is not als. Subsequently, right temporal artery biopsy that was done

Table 1: Traditional criteria for the classification of Giant Cell (Temporal) Arteritis Criterion Definition Age at onset of disease ≥ 50 years Development of symptoms or findings beginning at the age of 50 or older Recent onset of headache New onset of or new type of localized pain in the head Temporal artery abnormality Tenderness of temporal artery to palpation or decreased pulsation unrelated to arteriosclerosis of cervical arteries Elevated erythrocyte sedimentation rate Erythrocyte sedimentation rate ≥ 50 mm per hour according to the Westergren method Abnormal findings on biopsy of temporal artery Artery-biopsy specimen shows vasculitis characterized by a predominance of mononuclear-cell infiltrates or granulomatous inflammation, usually with multinucleated giant cells

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on the third day confirmed the diagnosis of GCA. She was Large, multi-centre, randomised, double-blind, placebo-con- also started on aspirin and low molecular weight heparin. Her trolled studies are required to define the role of methotrexate headache and odynophagia settled in two days but impairment and the immunosuppressants as corticosteroid-sparing drugs of vision in the left eye could not be halted. in GCA. A recent pilot study found that infliximab was effica- cious in patients with corticosteroid-resistant GCA.11 GCA causes visual dysfunction from involvement of a variety of different structures. Although early treatment may occa- References sionally result in the resolution of visual deficit, most patients 1. Horton JC. Disorders of the eye. In: Braunwald E, Fauci SA, Kasper DL, Hauser SL, who lose vision from GCA do not improve. It is imperative Longo DL, Jameson JL, editors. Harrisons Principles of Internal Medicine. 15th Ed, that clinicians diagnose the condition before visual loss occurs New York, McGraw Hill 2001;164-78. 2. Miller NR. Visual manifestations of temporal arteritis. Rheumatic Dis Clin North by combining a careful history and examination with appro- Am 2001;27:781–97. 3. Salvarani C, Contini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant cell priate laboratory studies. arteritis. N Engl J Med 2002;347:261-71. 4. Buana LM, Foroozan R, de Virgiliis M, Savino PJ. Heparin therapy in Giant cell arteritis. Br J Ophthalmol 2004;88:298-301. Patients in whom GCA is suspected should be treated imme- 5. Gonzalez-Gay MA, Blanco R, Rodriguez-Valverde V, Martinez-Taboada VM, Delgado- diately with systemic corticosteroids, after which a unilateral Rodriguez M, Figueroa M, et al. Permanent visual loss and cerebrovascular acci- dents in giant cell arteritis: Predictors and response to treatment. Arthritis Rheum or bilateral temporal biopsy should be performed for confir- 1998;41:1497-504. 2 6. Gonzalez-Gay MA, Garcia-Porrua C, Llorca J, Hajeer AH, Branas F, Dababneh A, et mation. Although thromboembolic occlusion is not a mecha- al. Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 nism in GCA, therapeutic benefit has been reported with the patients. Medicine (Baltimore). 2000;79:283-92. 3 7. Evans JM, O’Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and use of low-dose aspirin. Prevention of platelet aggregation is dissection in giant cell (temporal) arteritis. A population-based study. Ann Intern potentially effective even in patients with partial luminal oc- Med 1995;122:502-7. 8. Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, et al. The clusion. Progression of visual loss from GCA, despite intrave- American College of Rheumatology 1990 criteria for the classification of giant cell nous methylprednisolone therapy, may benefit by the addi- arteritis. Arthritis Rheum 1990;33:1122-8. 9. Wein FB, Miller NR. Unilateral central retinal artery occlusion followed by contralat- tion of heparin therapy.4 eral anterior ischemic optic neuropathy in giant cell arteritis. Retina 2000;20:301-3. 10. Stone JH, Calabrese LH, Hoffman GS, Pusey CD, Hunder GG, Hellmann DB. Vascu- litis. Rheumatic Dis Clin North Am 2001;27:677-728. What are the futuristic treatment modalities available for the 11. Cantini F, Niccoli L, Salvarani C, Padula A, Olivieri I. Treatment of longstanding active giant cell arteritis with infliximab: Report of four cases. Arthritis Rheum management of GCA? 2001;44:2933-5.

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