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Rheumatology 2001; 40: 1066-1068
© 2001 British Society for Rheumatology
Letters to the Editor |
Ocular involvement in Wegener's granulomatosis responding to intravenous cyclophosphamide
1 Rheumatology Unit, Ophthalmology Service and
2 Nephrology Service, Hospital Txagorritxu, Osakidetza, Vitoria, Spain
SIR, Wegener's granulomatosis (WG) is a systemic vasculitis of the upper and lower respiratory tracts together with glomerulonephritis. In addition, variable degrees of disseminated vasculitis, involving both small arteries and veins, may occur [1, 2]. Eye involvement is frequent and may range from a mild conjunctivitis to dacryocystitis, episcleritis, scleritis, granulomatous sclerouveitis, ciliary vessel vasculitis and retro-orbital mass lesions. Retinal vasculitis is described rarely [3]. Failure of antineutrophil cytoplasmic antibody (c-ANCA) titres to revert to normal levels may be associated with the potential for relapse in patients with ocular manifestations of Wegener's granulomatosis [4]. We present the case of a patient diagnosed with Wegener's granulomatosis who suffered a sudden loss of visual acuity first in the left eye and 3 months later in the right eye, while being treated with corticosteroids and oral cyclophosphamide (CYC) or methotrexate (MTX). Treatment with intravenous CYC led to the arrest of visual impairment and ameliorated visual acuity.
A 42-yr-old Caucasian man was diagnosed as having WG in December 1997. Segmental glomerulonephritis and pulmonary haemorrhage were presenting features. The patient was positive for c-ANCA (1:1260). Because the patient had severe and rapidly progressive disease, he was treated with high doses of corticosteroids and oral CYC (up to 3 mg/kg/day). This treatment controlled his pulmonary haemorrhage and ameliorated his glomerulonephritis and renal insufficiency. Shortly after discharge, the patient needed a large reduction in oral CYC to less than 1 mg/kg/day because of pancytopenia accompanied by two episodes of pneumonia due to Legionella pneumonie and Pseudomona aeruginosa. Corticosteroids were reduced gradually to 15 mg/day. In December 1998, while the patient was taking prednisone (10 mg/day) and oral CYC, he experienced a sudden loss of visual acuity in the left eye to the level of counting fingers. Ophthalmological examination showed thrombosis of the central vein of the retina with multiple haemorrhages, narrowing of arteries, thickening of veins, and some exudates (Fig. 1A
). c-ANCAs were detected (titre 1:640). Corticosteroids were increased to 1 mg/kg/day and oral MTX was introduced (7.5 mg/week). CYC was stopped. One month later, because of pancytopenia, MTX was discontinued, oral CYC was reintroduced and trimethoprim–sulphamethoxazole was added. Visual acuity did not change. In April 1999, coincident with a reduction in the corticosteroid dose, the patient experienced a new loss of visual acuity in the right eye to the level of 1/6. Ophthalmological examination showed multiple puntiforms and flame-shaped haemorrhages, as in the right eye. c-ANCAs were detected (titre 1:20). A computed tomograph of the orbit was normal. Three pulses of 1 g/day of methylprednisolone were administered and intravenous CYC (500 mg/m2 body surface) was initiated. The patient experienced recovery of visual impairment of the right eye and later of the left eye. At the time of writing, visual acuity is 6/6 in the right eye and 4/6 in the left eye. The patient has good tolerance of intravenous CYC. Ophthalmological examination now presents only hard exudates in the macular region in the left eye (Fig. 1B) and a normal appearance in the right eye. c-ANCAs are detectable (titre 1:160).
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Inflammatory eye involvement over the entire course of WG occurs in 30–60% of cases [1, 2, 5]. Ocular and ocular adnexal involvement in WG is the result of focal vasculitis of small arteries, arterioles and small veins, vascular thrombosis and haemorrhage, granulomatous inflammation, or the sequelae of chronic inflammation or ischaemia. Ophthalmic disease is the presenting feature in approximately 8–16% of patients. Proptosis and necrotizing keratoscleritis are the most common findings described. Retinal vasculitis per se is an exceedingly uncommon manifestation of WG and is frequently associated with other orbital involvement [3]. In a review of 140 patients with WG (40 patients with ocular and adnexial involvement), only seven patients (18%) demonstrated retinal disease with retinal haemorrhages and oedema; cotton-wool exudates and choroidal thickening occurred in four cases but there were no cases of isolated central retinal artery or vein occlusions [5]. Visual loss is an infrequent complication of WG. It has been described in 8% of patients in the course of the disease [1], but there is no information in this series about the specific cause of visual loss. Mechanisms contributing to decreased vision include vascular occlusion, macular oedema and inflammatory destruction of neurosensory tissues (retina or optic nerve) or structural tissues (e.g. corneoscleral tunic). Retinal vascular occlusion has been reported exceptionally [6, 7].
Treatment with corticosteroids and immunosuppressive agents has improved the prognosis of the disease dramatically. Oral CYC is associated with fewer disease relapses but more side-effects. Intravenous administration of CYC has ameliorated the tolerance of this drug but does not maintain remission or prevent relapses as effectively as oral administration [8]. Methotrexate has been used as an acceptable alternative form of therapy in patients who do not have immediately life-threatening WG or who have developed CYC toxicity. Unfortunately, patients with renal insufficiency (creatinine >2.5 mg/dl) have been excluded from trials and potential toxicity makes MTX a difficult treatment option [9].
Our patient is unusual. At the time of visual loss in the right eye, the c-ANCA titre was 1:20. There was no sign of pulmonary involvement or renal deterioration. The only predictor symptoms for relapse were polyarthralgias and c-ANCA positivity for the first eye, and there were no signs or symptoms for the second eye. Eighteen months after intravenous CYC therapy (approximately 10 g), the patient had a visual acuity of 6/6 in the right eye and 4/6 in the left eye and a creatinine clearance of 26 ml/min. At this time he was taking prednisone 2.5 mg/day, having developed secondary hyperparathyroidism.
This case illustrates (i) the possibility of relapse in the eyes of WG patients after systemic control of the disease and (ii) the efficacy of intravenous CYC in controlling visual impairment due to retinitis in cases of intolerance to oral CYC or secondary effects associated with it.
Notes
Correspondence to: E. Cuende, Unidad de Reumatología, Hospital Txagorritxu, José Atxotegi s/n, 01009 Vitoria, Spain. 
References
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