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Year : 2003  |  Volume : 51  |  Issue : 3  |  Page : 217-223

Ocular Manifestations of Wegener's Granulomatosis.Analysis of Nine Cases

Medical and Vision Research Foundation, Chennai, India

Correspondence Address:
J Biswas
Medical and Vision Research Foundation, Chennai
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Source of Support: None, Conflict of Interest: None

PMID: 14601846

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Purpose: To report a series of nine patients of Wegener's granulomatosis (WG) with diverse ocular and systemic manifestations. Methods: Retrospective analysis of nine consecutive patients seen between 1987 and 2002.
Results: The mean age at the time of diagnosis was 43.89 years (range: 33-56 years). Redness, pain and photophobia (8 patients) were the common presenting complaints. Sinusitis (6 patients) and arthralgia (6 patients) were the commonly associated systemic complaints. Necrotising scleritis with peripheral keratopathy (6 patients) was the most common ocular sign. Serum antibodies against the cytoplasmic component of neutrophils and monocytes (cANCA) were positive in 7 of 8 patients. Biopsy diagnosis was done in one patient for whom cANCA was not done. Cyclophosphamide and corticosteroids alleviated the symptoms in 6 patients. Ocular and systemic condition remained stable in 7 patients. One patient expired due to the severity of the disease and another patient was lost to follow-up. Conclusions: Scleritis with peripheral corneal involvement was the most commonly observed ocular manifestation of WG in our series. cANCA was a useful adjunct in the diagnosis of WG. When clinical and serologic findings were inconclusive, biopsy remained indispensable. A combination of cyclophosphamide and corticosteroids is essential and critical not only for the ocular condition but also for the survival of the patient.

Keywords: Wegner′s granulomatosis, necrotizing scleritis, proptosis, antineutrophilic cytoplasmic antibody, corticosteroids, cyclophosphamide

How to cite this article:
Biswas J, Babu K, Gopal L, Krishnakumar S, Suresh S, Ramakrishnan S. Ocular Manifestations of Wegener's Granulomatosis.Analysis of Nine Cases. Indian J Ophthalmol 2003;51:217-23

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Biswas J, Babu K, Gopal L, Krishnakumar S, Suresh S, Ramakrishnan S. Ocular Manifestations of Wegener's Granulomatosis.Analysis of Nine Cases. Indian J Ophthalmol [serial online] 2003 [cited 2023 Nov 30];51:217-23. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2003/51/3/217/14679

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Wegener's granulomatosis (WG) is a fulminant systemic disease of unknown aetiology involving multiple organ systems. We report here a series of nine consecutive patients with WG, seen over the last 15 years. In eight patients, ocular involvement led to the identification of the systemic disease. Their clinical presentations, responses to treatment and outcome are described, followed by a review of literature with a hope to providing guidelines for further management.

  Materials and Methods Top

Records of nine patients with an unequivocal diagnosis of WG, between 1987 and 2002, were retrieved. The diagnosis of WG was made as per the American Rheumatology criteria1 and the ELK classification systems2 in patients with systemic manifestations. The diagnosis of limited WG was made on a combination of clinical and serological findings. Diagnostic dilemmas were supported by biopsy, which established the diagnosis. The laboratory investigations included complete blood count, routine urine analysis, erythrocyte sedimentation rate (ESR), and chest X-ray for all patients. Special investigations like rheumatoid factor (in 8 patients), c-reactive protein (in 8 patients), cANCA (in 8 patients), computerised tomography (in 4 patients), renal function tests including renal biopsy (in 2 patients), orbital biopsy (in 3 patients), nasal biopsy (in 3 patients), bronchoalveolar lavage (in 2 patients) and conjunctival scraping to rule out infectious aetiology (in 1 patient) were done whenever required. Patients were contacted for follow-up information whenever necessary.

  Results Top

The patients included 6 men and 3 women. The mean age at time of diagnosis was 43.89 years (range: 33-56 years). Seven patients had the limited form of WG, while two patients had the complete form. Redness, pain and photophobia (8 patients) were the common presenting complaints. Sinusitis (6 patients) and arthralgia (6 patients) were the commonly associated systemic complaints. Necrotising scleritis with peripheral keratopathy (6 patients) was the most common finding noted in our series. The peripheral keratopathy seen in our series included peripheral corneal thinning (cases 5,8), stromal infiltrates (cases 1, 3, 7, 9) and peripheral ulcerative keratitis (cases 1,4). Diffuse and nodular scleritis were also seen in the milder forms of the disease. Orbital involvement was seen in only three patients. Laboratory investigations revealed elevated ESR and leucocytosis in the active stage of the disease in 8 patients. Case 8 was in the inactive stage of the disease and hence did not have leucocytosis. Chest X-ray revealed cavities and infiltrates in the lung in two patients. Haematuria was seen in 2 patients. Renal biopsy in these patients showed a crescentric glomerulonephritis. Eight patients were tested for cANCA; seven patients were positive (cases 1, 3, 4, 5, 6, 7, 9), and one patient (case 8) who was in the inactive stage of the disease, was negative. One patient (case 2) was not tested for cANCA as facilities were not available at that time. Biopsy showing granulomatous inflammation with necrotising vasculitis confirmed the diagnosis in this case. Rheumatoid factor was positive in 5 cases. Cyclophosphamide and corticosteroids alleviated the symptoms in 6 of 7 patients. The ocular and systemic condition remained stable in seven patients. One patient expired due to the severity of the disease and another was lost to follow-up.

The ocular manifestations, systemic extent of disease, management and outcome in the nine patients of WG are listed in [Table - 1]. The results of the laboratory investigations are listed in [Table - 2]. One case (Case 1) is presented for illustration.

  Case report Top

A 33-year-old male presented in December 2001 with a history of pain, redness and photophobia in the left eye of 4 months' duration. He gave a history of taking oral corticosteroids following which he developed severe cough and fever. He was on antituberculosis drugs for a diagnosis of an abscess in the left lung. Systemic history was remarkable, including a productive cough with one episode of haemoptysis and early morning knee and the ankle joint stiffness.

On examination, his best corrected visual acuity was 6/12 in both eyes. Slitlamp examination of the right eye revealed sectoral superior scleral congestion with stromal infiltrates at the limbus. The left eye examination revealed necrotising scleritis with areas of uveal prolapse superiorly (between 10.30 to 12 o' clock positions) [Figure - 1]. There were 2+ aqueous and vitreous cells (Hogan's grading). Fundus examination of the right eye was normal and the left eye showed an area of retinitis corresponding to the area of necrotizing scleritis along with haemorrhages and retinal oedema. Intraocular pressures were normal. Earlier investigations by his referring ophthalmologist included ESR of 35mm/1st hour, and radiographic evidence of left lung cavity. On repeat investigation the ESR was raised to 114mm 1st hour, and the serial chest X-rays showed progression of the left lung cavity and appearance of another cavity in the right lung [Figure - 2]. Bronchoalveolar lavage revealed Pseudomonas fluorescens . Direct smear and culture for Mycobacterium tuberculosis were negative. The patient was started on systemic antibiotics (oral norfloxacin 400 mg twice daily, oral metronidazole 200 mg twice daily, intravenous gentamicin 80 mg twice daily) and hourly instillation of prednisolone acetate eye drops. Four days later, his systemic condition worsened with development of palpable purpuras and ecchymosis on the arms, forearms, legs [Figure - 3] and back and swelling of the ankle and the knee joints. Ocular examination now showed progression of the retinitis towards the posterior pole [Figure - 4]. Blood tests showed an increased blood urea (47mg%) and serum creatinine (4mg%). Renal biopsy showed crescentric glomerulonephritis [Figure - 5]. CT scan of the thorax showed minimal pleural and pericardial effusion with cavities in the right and left lungs [Figure - 6]. cANCA was positive [Figure - 7]. A diagnosis of WG was made. Ultrasound-guided aspiration of the fluid from the cavity in left lung showed a haemorrhagic, sterile fluid. In view of his elevated blood urea and creatinine levels, he underwent dialysis. He was given a pulse dose of intravenous cyclophosphamide (500 mg/m[2] body surface area) and methyl prednisolone (1 gm/day intra-venous for 3 days) followed by oral cyclophosphamide (2 mg/kg/day) and oral prednisolone (1 mg/kg body weight) under antibiotic cover. Oral cyclophosphamide was continued for 6 months. His haematological status was closely monitored. At the 6-month follow-up, vision was 6/9 in the right eye and 6/24 in the left eye. His ocular and systemic condition thereafter remained stable.

  Discussion Top

The complete form of WG is characterised by a triad of necrotising granuloma of the upper and lower respiratory tract, systemic vasculitis and focal necrotising glomerulonephritis.[3] The limited form is characterised by an isolated organ involvement, commonly the lungs and the airways.[4],[5] Ocular involvement was more common in the limited form in our series. This has been noted in earlier reports.[6],[7]

Only a few reports of WG in the Indian population exist.[7],[8],[9],[10] In our series, all nine patients had ocular manifestations.

Incidence of ocular involvement in WG varies from 29 to 79%. [11],[12],[13],[14],[15] Ocular involvement can be either due to an extension from the adjacent paranasal sinuses (contiguous) or as a result of focal vasculitis (nonconti-guous).[11],[12] Eight of our nine cases initially presented to an ophthalmologist, suggesting that the ocular involve-ment may be the presenting manifestation of an underlying systemic vasculitides.

Orbital pseudotumour, nasolacrimal obstructions, fistulas, scleritis with peripheral keratopathy, kerato-conjunctivitis sicca, uveitis, retinitis, retinal vascular occlusions, exudative retinal detachments, and optic neuritis are the various ocular manifestations reported in WG.[6],[7],[11],[12],[13],[14],[15] While necrotising scleritis with peripheral keratopathy was the most common presentation in our series, orbital involvement is more frequently reported in the Western literature. [11],[12],[13],[14],[15] Orbital involvement was seen in only three of our patients. This is comparable to the other series from India.[7] The peripheral keratopathy seen in our series was similar to that reported by Sainz de la Maza et al.[14] Diffuse and nodular scleritis was also seen in the milder forms of the disease.

Laboratory findings support or confirm the diagnosis of WG. We noted elevated ESR and leucocytosis in the active stage of the disease. Radiological investigations like chest X-ray and computerised tomography can detect pulmonary involvement. It is necessary to routinely order a chest X-ray in all patients of suggested WG. Routine urine analysis detects renal involvement. Renal biopsy supports the diagnosis of WG.

Serum antibodies against the cytoplasmic component of neutrophils and monocytes (cANCA) form a useful adjunct in the diagnosis of WG. [6], [17],[18],[19] Indirect immunofluorescence is currently the standard test for ANCA screening.[6] Between 80% and 95% of all ANCA found in WG is cANCA. ANCA specificity in WG is about 98% but the sensitivity depends on the extent and disease activity.[20] When the orbit and paranasal sinus are involved, the diagnosis is established by biopsy. Presence of granulomatous inflammation, necrosis and vasculitis are the characteristics.[21]

Prior to the widespread availability of cANCA the American College of Rheumatology established four major criteria to distinguish WG from other systemic vasculitides.[1] The presence of two or more of the following has 88.2% sensitivity and 92% specificity for WG. (1) nasal or oral inflammation (painless or painful oral ulcers or bloody nasal discharge) , (2) abnormal chest X-ray (nodules, cavities, infiltrates), (3) abnormal urinary sediment (red cell casts or five red blood cells per high power field), (4) Granulomatous inflammation on biopsy. The ELK classification system proposed by DeRemee et al[2] utilises ANCA results. Under this system, any typical manifestation in the upper respiratory tract, lung or the kidney supported by typical histopathology or a positive cANCA test qualifies for the diagnosis of WG.

Association of rheumatiod arthritis[12] and similarly with tuberculosis[7] is not uncommon. The presence of rapidly progressing scleritis with corneal involvement or an orbital disease in association with multisystem involvement (Upper respiratory tract, lung, kidney, joints, systemic vasculitis) may help in clinically differentiating WG from rheumatoid arthritis and tuberculosis. Positive cANCA is a useful tool for screening.

Management of WG requires a multisystem approach in close coordination with an internist. Oral corticosteroids alone are not sufficient to abort the progression of the disease. They only help to gain time before starting immunosuppressives. Cyclophos-phamide is the most commonly used immunosuppres-sive agent in WG. [6],[7], [11],[12],[13],[14],[15]

There is no difference in the treatment of the systemic and the limited forms of WG. In this series corticosteroids and cyclophosphamide were given in 7 patients and alleviated symptoms in 6 patients. One patient, however, expired due to the end-stage of the disease. The treatment protocol followed for WG is given in [Table - 3]. Exacerbations are common in the first two years after diagnosis. Drugs like azathioprine, cyclosporine A and methotrexate may be used when the disease is in remission. [6],[12],[13],[14],[15]

This communication highlights the various manifestations of this grave, and rapidly fulminant disease. An ophthalmologist could be the first clinician to encounter such a patient, as necrotising scleritis is one of the common presentations. We emphasise that WG must be kept in mind and cANCA should be done in such cases. Early treatment with cyclophosphamide and corticosteroids reduces both ocular and systemic morbidity in this otherwise life-threatening systemic vasculitis.

  References Top

Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum 1990;33:1101- 07.  Back to cited text no. 1
DeRemee RA. The nosology of Wegener's granulomatosis utilizing the ELK format augmented by cANCA. Adv Exp Med Biol 1993;336:209-15.  Back to cited text no. 2
Godman GC, Churg J: Wegener's granulomatosis. Pathology and review of the literature. Arch Pathol 1954;58:533- 53.  Back to cited text no. 3
Casson SM, Coles DT, Harrison E. The concept of limited forms of Wegener's granulomatosis. Am J Med 1970;49:366-79.  Back to cited text no. 4
Carrington CB, Leibow AA. Limited forms of angiitis and granulomatosis of Wegener's type. Am J Med 1966;41:497-527.  Back to cited text no. 5
Harman LE, Margo CE. Wegener's granulomatosis. Survey of Ophthalmology 1998;42:458-80.  Back to cited text no. 6
Bambery P, Sakhuja V, Gupta A, Behera D, Kaur U, Bhusnurmath SR et al. Wegener's granulomatosis in north India. An analysis of eleven patients. Rheumatol Int 1987;7:243-47.  Back to cited text no. 7
Singh YN, Sharma SK, Agarwal J, Pande JN, Malaviya AN. Wegener's granulomatosis - successful treatment with cyclophosphamide and steroids. Indian J Chest Dis Allied Sci 1991;33:143- 47.  Back to cited text no. 8
Handa R, Wali JP, Aggarwal P, Wig N, Biswas A, Kumar AK. Wegener's granulomatosis with complete heart block. Clin Exp Rheumatol 1997;15 97-99.  Back to cited text no. 9
Singh YN, Malaviya AN, Sharma SK, Kumar A, Wali JP, Dasch SC, Bhuyan UN. Wegener's granulomatosis in northern India. J Assoc Physicians India 1992;40:594- 96.  Back to cited text no. 10
Straatsma BR. Ocular manifestations of Wegener's granulomatosis. Am J Ophthalmol 1957;144:789-99.  Back to cited text no. 11
Bullen CL, Liesegang TJ, McDonald TJ, DeRemee RA. Ocular complications of Wegener's granulomatosis. Ophthalmology 1983;90:279-90.  Back to cited text no. 12
Haynes BF, Fishman ML, Fauci AS, Wolff SM. The ocular manifestations of Wegener's granulomatosis. Fifteen years experience and review of the literature. Am J Med 1977;63:131-41.  Back to cited text no. 13
Charles SJ, Meyer PA, Watson PG. Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior inflammatory disease. Br J Ophthalmol 1991;75:201-7.  Back to cited text no. 14
Spalton DJ, Graham EM. Page NGR, Sanders MD. Ocular changes in limited forms of Wegener's granulomatosis. Br J Ophthalmol 1981;65:553- 63.  Back to cited text no. 15
Sainz de la Maza, Foster CS, Jabbur NS, Baltatzis S. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. Arch Ophthalmol 2002;120:15-19.  Back to cited text no. 16
Pulido JS, Goenken JA, Nerad JA, Sobol WM, Folberg R. Ocular manifestations with circulating antineutrophil cytoplasmic antibodies. Arch Ophthal-mol 1990;108:845-50.  Back to cited text no. 17
Soukiasian SH, Foster CS, Niles JL, Raizman MB. Diagnostic value of antineutrophilic antibodies in scleritis associated with Wegener's granulomatosis. Ophthalmology 1992;99:125- 32.  Back to cited text no. 18
Fong LP, Sainz de la Maiza M, Rice BA, Kupferman AE, Foster CS. Immunopathology of sclera. Ophthalmology 1991;98:472-79.  Back to cited text no. 19
Nolle B, Specks U, Ludemann J, Rohrbach MS, De Remee RA, Gross WL. Anticytoplasmic antibodies: Their immunodiagnostic value in WG. Ann Intern Med 1989;111:28-40.  Back to cited text no. 20
Kalina PH, Lie JT, Campbell RJ, Garrity JA. Diagnostic value and limitations of orbital biopsy in Wegener's granulomatosis. Ophthalmology 1992;99:120-24.  Back to cited text no. 21


  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]

  [Table - 1], [Table - 2], [Table - 3]

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