Year : 2002 | Volume
: 50 | Issue : 2 | Page : 135--137
Limited wegener's granulomatosis presenting as multiple retinal vascular occlusions
R Shenoy, el Nour Elagib, H al Siyabi, A Amer
Department of Ophthalmology, Sultan Qaboos University Hospital, P.O. Box 38, P.C 123, Al Khoud, Muscat, Sultanate of, Oman
Department of Ophthalmology, Sultan Qaboos University Hospital, P.O. Box 38, P.C 123, Al Khoud, Muscat, Sultanate of
In the early stages of Wegener«SQ»s granulomatosis, and in the atypical forms, the classic clinicopathologic features of the disease are often absent, delaying diagnosis. Recognition of the disease and its variant is aided by serological markers
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Shenoy R, Elagib eN, al Siyabi H, Amer A. Limited wegener's granulomatosis presenting as multiple retinal vascular occlusions.Indian J Ophthalmol 2002;50:135-137
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Shenoy R, Elagib eN, al Siyabi H, Amer A. Limited wegener's granulomatosis presenting as multiple retinal vascular occlusions. Indian J Ophthalmol [serial online] 2002 [cited 2020 Apr 4 ];50:135-137
Available from: http://www.ijo.in/text.asp?2002/50/2/135/14805
Wegener's granulomatosis, first described by Freiderich Wegener, is a fatal multisystem disease. It presents with a distinct clinical pattern of necrotising granulomas involving the respiratory tract, focal necrotising vasculitis, and focal necrotising glomerulonephritis. Wegener's glomerulonephritis and carries a high morbidity and mortality rate. The disease entity "Limited Wegener's Granulomatosis" was first proposed by Carrington and Leibow. This form of the disease has no renal involvement, takes a milder course, and has a better prognosis. However, it could progress to the classic form. Whether this is a separate clinical entity or an early stage of the classic form is still unclear. Ocular involvement occurs with equal frequency in both classic and limited form of the disease. Retinal vascular occlusion, as a primary ocular manifestation of the disease, is unusual. Since 1960 only 5 cases have been reported in ophthalmic literature (Medline search).
A 13-year-old girl presented to the ophthalmic emergency, in October 1998 with a history of sudden loss of vision in her left eye of a week's duration. She complained of generalised weakness and weight loss. and also noticed loss of scalp hair approximately 2 months prior to the loss of vision in her left eye.
General examination revealed a frail looking girl, with scant hair on her scalp. She had discrete, non-tender lymphadenopathy involving the axillary and the cervical nodes and mild hepatosplenomegaly.
Her best corrected visual acuity in the right eye was 6/6 and in the left eye counting fingers (CF) close to face. External examination of the eye and extraocular eye movements were normal. The left pupil was semi-dilated reacting sluggishly to direct light stimulation. Intraocular pressure was normal in both eyes. Visual field (Goldman perimeter) was normal in her right eye but could not be traced in the left eye. The right eye fundus was normal The left eye fundus showed a pale optic disc with well defined margins and multiple occlusions in the superior and inferior temporal arterioles. There was retinal ischaemia involving the posterior pole (and macula) with scattered superficial haemorrhages and soft exudates. Telengiectatic changes were present. [Figure:1] and [Figure:2]. Fundus Fluorescein angiogram showed absent filling of the dye in the arterioles arising from the superior and inferior arcades, confirming their occlusion. The foveal avascular zone was widened, indicating ischemia. The telengiectatic vessels showed irregular faint staining of their vessel walls. There was no leakage of dye as such [Figure:3]. The angiogram in the right eye was normal.
Laboratary investigations revealed normochromic normocytic anaemia (haemoglobin 9g/L) and raised erythrocyte sedimentation rate (65 mm/1st hour) Total leucocyte count of 3.3 x 109 / L (normal 3.3-11 x 109/ L), platelet count of 250 x 109/ L (normal 140-440 x 109/L), 'C 'reactive protein was less than 13.8, (normal 0-94nmol/L). The sickle cell test was negative and liver function tests were normal.
Immune analysis showed normal complement levels for C3 and C4. Daily 24-hour urine protein was normal (0.060 g) (range 0.050-0.80 g). Rheumatoid factor was negative. Antinuclear antibodies were weakly positive (1:160 fine speckled). and antineutrophil cytoplasmic antibodies (cANCA) were strongly positive in a titre of more than 1:640. Serum immunoglobulin levels were normal for Immunoglobulin M, and Immunoglobin A, but Immunoglobulin E and Immunoglobin G were raised [(1558-20,000Kiu/L) (normal IgE 0-150Kiu /L) and (17.7 g/L) (normal IgG 5.8-13.7 g/L) respectively]. Anti streptolysin O levels were normal (180 units). Tests for lupus anticoagulant activity and anti cardiolipin antibodies were normal.
Serology for Toxoplasma, Rubella, Cytomegalovirus, Herpes simplex virus and Human immuno deficiency virus were negative. Blood urea was 2.5mmol/L (normal 2.5 - 7.5 mmol/L) Serum electrolytes (Na 136 mmol/L (normal 136-146 mmol/L), K - 4.7 mmol/L (3.5 -5.0 mmol/L), Cl-98 mmol/L (normal 97-108 mmol/ L) and serum creatinine (42umol/L) (normal 40-110 umol/L) were normal. Xray chest, Mantoux test and computed tomogram of the orbit were normal. Ultra sound abdomen showed minimal enlargement of the liver and spleen. The kidneys were normal in size and echotexture.
In view of the multiple vascular occlusions and the high cANCA titres, and in the absence of renal or pulmonary involvement, she was diagnosed to having Wegener's granulomatosis probably of the limited type. She was treated with monthly doses of intravenous pulse methylprednisolone 500mg and cyclophos-phamide 500mg until remission.
Clinical response was noted by weight gain, regression of cervical lymphadenopathy and hepatosplenomegaly. There was regrowth of scalp hair and resolution of serum markers. The cANCA levels were negative by the 3rd dose (cANCA levels - 1: 160 and 1:80 after the 1st and 2nd dose respectively), but the vision in her left eye remained poor (CF 1metre) due to optic atrophy secondary to the multiple retinal vascular occlusions. Remission was maintained with weekly oral doses of methotrexate (7.5mg) and daily prednisolone (10-mg). She was closely followed up for 2 years. No clinical or serological relapse was noted. Fibrous bands extending over the temporal vessels were noted in the left eye in the last follow-up visit in January 2001 [Figure:4].
Wegener's granulomatosis is a necrotising granulomatous vasculitis of unknown aetiology. The complete (classic) form manifests with the triad of necrotising granulomas involving the respiratory tract, kidney and blood vessels. In the limited form, the kidney is spared. The limited form runs a milder course and responds well to treatment. Elevated serum cANCA occur in both forms., These are autoantibodies belonging to the class of Imunoglobulin G and are directed against the neutrophil cytoplasmic determinants., The antibody titres correlate with disease activity, increasing during reactivation of the disease. The titres decrease with treatment, becoming negative in approximately 12 weeks following treatment.,
Ocular involvement in Wegener's Granulomatosis could either be due to focal vasculitis or to extension of the disease process from the adjacent upper respiratory tract. It has been reported with a frequency of 28-77% by various authors., The presentations include conjunctivitis, episcleritis, scleritis, uveitis, retinal phlebitis, optic neuropathy, obstruction of the nasolacrimal duct and unilateral or bilateral proptosis.
Retinal involvement, in either form of the disease, is most often secondary to ocular or orbital manifestations. This includes retinal phlebitis, vascular occlusions, haemorrhages, exudates, acute retinal necrosis, macular oedema, choroidal folds and retinal pigmentary changes. Retinal lesions without any other associated ocular or orbital disease are unusual.
Our patient had multiple retinal vascular occlusions, superficial retinal haemorrhages, soft exudates, telengiectatic changes, and pallor of the optic nerve in the left eye with no evidence of orbital, or ocular disease. She also had unexplained weight loss with alopecia, discrete cervical lymphadenopathy and hepatosplenomegally. Her liver and renal functions were normal and so was the Chest x-ray. A diagnosis of Limited Wegener's granulomatosis was made after excluding all other causes of retinal vascular occlusions. The absence of involvement of kidney and a raised serum cANCA further supported the diagnosis. She responded clinically as well as serologically to treatment; the cANCA levels were negative approximately 3 months after treatment. The titres remained negative throughout the 2 year period of follow up and during this period there was no clinical activity or progression of lesions in the eyes. Fibrotic changes along the temporal retinal vessels, also suggested local regression.
Retinal lesions without any associated ocular or orbital involvement, are a very unusual presentation of either classic or limited from of Wegner's granulomatosis. While histopathology has been the only definitive means of confirmtion, in the absence of typical and complete clinical and histopathological evidence, demonstration of raised serum levels of cANCA aid in the diagnosis of the disease, as in our case. A raised cANCA level can also occur in other infectious and non - infectious diseases. Nevertheless, the classic cytoplasmic pattern has been found to be specific and sensitive for the disease.
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