The ocular manifestations of Wegener's granulomatosis: Fifteen years experience and review of the literature

doi:10.1016/0002-9343(77)90125-5

The American Journal of Medicine

Volume 63, Issue 1, July 1977, Pages 131-141

https://doi.org/10.1016/0002-9343(77)90125-5 Get rights and content

Abstract

Ocular manifestations of Wegener's granulomatosis may occur secondary to contiguous granulomatous sinusitis or as a result of focal vasculitis. Contiguous granulomatous sinus disease causes nasolacrimal duct obstruction, proptosis and ocular muscle or optic nerve involvement. Focal vasculitis unrelated to contiguous upper respiratory tract disease is manifested by conjunctivitis, episcleritis, scleritis, corneoscleral ulceration, uveitis, and granulomatous vasculitis of the retina and optic nerve. A review of 29 cases of Wegener's granulomatosis and three cases of lymphomatoid granulomatosis studied over the past 15 years at the National Institute of Allergy and Infectious Diseases (NIAID) disclosed single or multiple ocular manifestations of disease in 15 patients (47 per cent). The pattern of ocular disease, its relationship to systemic involvement, diagnostic methods and the response to therapy are discussed.

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Citation Excerpt :
Contiguous granulomatous sinus disease may manifest as nasolacrimal duct obstruction, proptosis and involvement of the ocular muscles or the optic nerve. Focal vasculitis manifests as conjunctivitis, episcleritis, scleritis, corneoscleral ulceration, uveitis and vasculitis of retina [7]. Similar to other systemic immune mediated disease such as relapsing polychondritis necrotizing scleritis leading to perforation of sclera and loss of sight are the most dreaded ocular complications [14,15].
Ocular and orbital involvement in Granulomatosis with polyangiitis (GPA) is common. GPA can lead to life and sight threatening complications due to necrosis and tissue melting.
We report four cases presenting with ocular pain and redness for varied durations. One had diminution of vision. All of them had deep sectoral/diffuse congestion with one having scleral thinning. All were diagnosed with anterior necrotizing/non-necrotizing scleritis. One had associated penetrating ulcerative keratitis. Topical steroids and systemic non-steroidal anti-inflammatory drugs were started in all cases and rheumatology consultation was taken. Pertinent investigations were sent, and GPA was diagnosed. Intravenous immunosuppressive regimens and oral steroid were started and significant improvements were seen, preventing untoward complications.
Scleritis could be manifesting feature of GPA so cautious history taking and evaluation is important. Management often requires multidisciplinary care and ocular features could be the reference guidelines to adjust dose of systemic medications of GPA.
Conjunctivitis as a manifestation of Wegener's Granulomatosis
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To report a case of prolonged conjunctivitis as the manifestation of Granulomatosis with polyangiitis (GPA).
A 37-year-old man presented with prolonged conjunctivitis which had persisted for one month. He was taking medication for his conjunctivitis without any response. A slit-lamp examination revealed conjunctivitis and scleritis in the right eye. Conjunctivitis, 360-degree peripheral corneal thinning, corneal perforation, and scleritis were seen in the left eye.
Emergency penetrating keratoplasty was performed to treat the patient's corneal perforation. After a consultation with the Internal Medicine Department, the patient was suspected of having GPA with positive cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Functional endoscopic sinus surgery was performed to treat right maxillary sinusitis, and a biopsy of the maxillary sinus mucosa was obtained. The pathology report showed granuloma and vasculitis with severe acute and chronic inflammation and few eosinophils; thus, the diagnosis was confirmed.
Because prolonged conjunctivitis occurs only rarely in association with systemic disease, ophthalmologists should be aware of this potential, particularly in patients with GPA.
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There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies – to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein – have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular Neuroretinitis) are of obscure pathogenesis but an autoimmune disorder of the post-infectious type is plausible. Visual loss in autoimmunity is an expanding field: the most significant advances in research have resulted from taking a well characterised phenotype and making educated guesses at the possible molecular targets of autoimmune attack.
Rationale for a diagnostic approach in non-Graves' orbital inflammation-Report of 61 patients
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Les syndromes inflammatoires orbitaires regroupent une grande variété de processus intraorbitaires d’aspect inflammatoire très différents dans leurs présentations cliniques et leurs pronostics. On préfère actuellement différencier les inflammations orbitaires, dites spécifiques, pour lesquelles une étiologie a pu être identifiée, des syndromes inflammatoires orbitaires idiopathiques (SIOI) pour lesquelles l’étiologie reste inconnue et l’histologie non spécifique.
Le but de ce travail est de proposer une approche diagnostique efficace au clinicien devant prendre en charge une inflammation orbitaire non basedowienne.
Il s’agit d’une étude rétrospective et prospective regroupant 61 patients pris en charge pour une inflammation orbitaire non basedowienne entre mai 1999 et mai 2013 dans les services d’ophtalmologie des CHU de Nice et Limoges. Nous avons inclus 17 inflammations spécifiques, 19 lymphomes orbitaires et 25 syndromes inflammatoires orbitaires idiopathiques. Les patients ont été divisés en deux groupes. Trente-six patients (groupe 1) ont bénéficié d’une biopsie en première intention, alors que pour les vingt-cinq autres (groupe 2), le test thérapeutique a été initié d’emblée sans biopsie et nous avons ainsi pu comparer ces deux démarches en termes de rentabilité diagnostique et délai d’obtention d’une étiologie spécifique.
Nos résultats statistiques démontrent qu’une approche sans biopsie en 1^re intention conduit à un nombre de diagnostics spécifiques statistiquement très inférieur à celui obtenu par la démarche avec une biopsie en première intention. De la même manière, le risque de méconnaître une inflammation spécifique (d’où traitement inadapté avec risque de séquelles fonctionnelles et risque vital de méconnaître une pathologie lymphoproliférative) est très nettement supérieur dans le cas où l’on ne réalise pas de biopsie en 1^re intention. Enfin, le délai moyen entre la première consultation avec l’ophtalmologiste spécialisé et l’obtention d’un diagnostic spécifique a été de 1 mois avec la démarche 1 alors qu’avec la démarche 2, ce délai était presque trois fois supérieur avec une moyenne de 2,91 mois (p < 0,01).
Notre étude montre que la biopsie doit donc être le point d’orgue de la prise en charge diagnostique. Le test thérapeutique n’est effectué en 1^re intention qu’exclusivement dans les myosites ou dans les localisations où la biopsie engage le pronostic fonctionnel. Il ne doit être réalisé qu’après la biopsie dans tous les autres cas. Bien sûr dans tous les cas de rechute ou de récidive après ce traitement, la biopsie doit être réalisée ou renouvelée.
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To propose an efficient diagnostic approach for clinicians managing patients with non-Graves’ orbital inflammations.
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Our study shows that biopsy should be the mainstay of diagnostic management. A trial of empiric treatment is only performed first in myositis or in locations where biopsy could jeopardize functional prognosis. It should only be done after biopsy in all other cases. Of course, in all cases of relapse or recurrence after treatment, biopsy should be performed or repeated.
The diagnostic work-up of a patient with an orbital inflammatory process must of course include blood testing and orbital imaging, but also a systematic primary biopsy for histological examination in the vast majority of cases. It must be repeated at least in the case of any doubt about the diagnosis or in the case of any recurrence or resistance to treatment.

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¹: From the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, and the Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland.

View full text

ReviewThe ocular manifestations of Wegener's granulomatosis: Fifteen years experience and review of the literature

Abstract

Am J Med

Am J Med

Am J Med

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Med

Am J Med

Hum Pathol

Am Heart J

Am J Med

Am J Med

J Thorac Cardiovasc Surg

Am J Med

Ann Thorac Surg

Lancet

Am J Med

Wegener's granulomatosis. Pathology and review of the literature

Arch Pathol

Wegener's granulomatosis. Studies in 18 patients and a review of the literature

Medicine (Baltimore)

Pulmonary angiitis and granulomatosis

Am Rev Respir Dis

Giant cell granuloma of the respiratory tract (Wegener's granulomatosis)

Br Med J

Limited form of Wegener granulomatosis. Eye involvement as a major sign

JAMA

Pseudotumor of the orbit and limited Wegener's granulomatosis

Ann Intern Med

Wegener's granulomatosis

Ann Intern Med

Granulomatous sclerouveitis

Arch Ophthalmol

Marginal (ring) corneal ulcer as presenting manifestation of Wegener's granuloma. A clinicopathologic study

Trans Am Acad Ophthalmol Otolaryngol

Case records of the Massachusetts General Hospital

N Engl J Med

Wegener's granulomatosis and corneal-scleral ulcer

JAMA

The histopathology of perilimbal ulceration in Wegener's granulomatosis

Arch Ophthalmol

Corneoslceral lesions in periarteritis nodosa and Wegener's granulomatosis

Trans Am Ophthalmol Soc

Inflammatory pseudotumor of the orbit

Br J Ophthalmol

Pseudotumor of the orbit and Wegener's granuloma

Lancet

Neurological complications of Wegener's granulomatosis

Arch Neurol

Cyclophosphamide therapy in Wegener's granulomatosis

N Engl J Med

The use of alkylating agents in the treatment of Wegener's granulomatosis

Ann Intern Med

Wegener's granulomatosis. Treatment with cytotoxic agents and adrenocorticoids

Ann Intern Med

Radiation therapy of midline granuloma

Ann Intern Med

Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc

Br J Opthalmol

Wegener's granulomatosis

Wegener's granulomatosis

Ann Otol Rhinol Laryngol

Wegener's granulomatosis—a triad

JAMA

Wegener's granulomatosis

Am Rev Respir Dis

Wegener's granulomatosis. A clinico-pathologic study of four cases

Ann Intern Med

Review
The ocular manifestations of Wegener's granulomatosis: Fifteen years experience and review of the literature