The Clinical and Pathologic Constellation of Wegener Granulomatosis of the Orbit

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<ul><li><p>The Clinical and Pathologic Constellation of Wegener Granulomatosis of the Orbit </p><p>Stephen R. Perry, MD,1 Jack Rootman, MD/,3 Valerie A. White, MD2,3 </p><p>Purpose: Wegener granulomatosis (WG) may present as an orbital mass without obvious upper respiratory or systemic features. The authors examined the clinical and pathologic features of a series of cases of orbital WG to define the features of presentation and progression of this disorder. </p><p>Methods: Thirteen subjects with orbital presentations of WG were identified from the University of British Columbia Orbit Clinic index of diseases. Clinical features were correlated with the results of computed tomography in 12 cases and orbital biopsy in 11 cases. Antineutrophil cytoplasmic antibody (c-ANCA) testing was performed in five cases. </p><p>Results: The main ocular symptoms were decreased vision, redness, and ocular and facial pain, whereas the main signs were proptosis, scleritis, and lid inflammation. Progression was marked by an increased incidence of bilaterality and systemic features. Ear, nose, and throat features were discovered at presentation in 11 cases and became universal during the follow-up period. Initial antineutrophil cytoplasmic antibody test results were negative in five patients but became positive later in three patients. Orbital biopsy specimens typically had features of mixed inflammation, fat disruption, and small areas of necrosis. The combination of cyclophosphamide and oral steroids was highly effective in terminating disease episodes. </p><p>Conclusions: Orbital WG can be recognized by a constellation of clinical and radio-logic findings with evidence of an often erosive, infiltrating, and restrictive fibrotic, inflam-matory mass. Concurrent ear, nose, and throat or specific ocular findings such as scleritis with typical limbal infiltrate can occur. Biopsy results show mixed inflammation with evidence of necrosis that must not be regarded as a nonspecific finding. Ophthalmology 1997; 1 04:683-694 </p><p>Over time, we have become impressed by the protean clinical and diagnostic features of orbital Wegener granu-lomatosis (WO). This disorder has a broad range of pre-sentations and associations. It often is clinically and </p><p>Originally received: February 13, 1996. Revision accepted: December 12, 1996. I Department of Ophthalmology, Kidderminster General Hospital, Kid-derminster, W orcestershire, England. 2 Department of Ophthalmology, University of British Columbia and the Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, Canada. </p><p>pathologically misdiagnosed or diagnosed late, which may lead to grave visual or systemic consequences. Ad-vances in treatment over the past decade have greatly improved the prognosis, particularly when diagnosis is made early. These concerns prompted a retrospective re-view of our experience at the University of British Colum-bia Orbit Unit. Results suggest that a constellation of clinical, radiologic, and pathologic features may facilitate earlier recognition of this disease. Prompt initiation of effective, specific therapy leads to optimal outcome for </p><p>3 Department of Pathology, University of British Columbia and the Van-couver Hospital and Health Sciences Centre, Vancouver, British Colum-bia, Canada. Presented at the American Society of Ophthalmic, Plastic and Recon-structive Surgery Annual Meeting, Chicago, Illinois, November 13, 1993; the Verhoeff Society Meeting, Rochester, Minnesota, May 12-</p><p>15, 1994, and the International Symposium on Eyelids, the Orbit and the Lacrimal System-XXVIlth International Congress of Ophthalmology, Toronto, Ontario, June 24-25, 1994. Reprint requests to Jack Rootman, MD, Department of Ophthalmology, University of British Columbia, 2550 Willow St, Vancouver, British Columbia, Canada, V5Z 3N9. </p><p>683 </p></li><li><p>Ophthalmology Volume 104, Number 4, April 1997 </p><p>what initially may be a relatively benign manifestation of WG. </p><p>Materials and Methods </p><p>Thirteen subjects were identified from the index of dis-eases maintained by the University of British Columbia Orbit Unit. Data presented here include observations from </p><p>684 </p><p>our clinic as well as information from distant referring centers that, for geographic reasons, shared in the follow-up care. </p><p>This retrospective study was made possible by formal-ized and meticulous recording of orbital disease l and by information available through systemic evaluations, or-bital biopsy material (11 cases, 1 as an outside pathology consult), and computed tomography (CT) (12 cases). The diagnosis of WG was made from the observed overall </p></li><li><p>Perry et al . Wegener Granulomatosis of the Orbit </p><p>Figure 1. A, a 21-year-old man presented in January 1987 with a I-year history of recurrent, progressive, bilateral lid swelling associated with injection and proptosis. He also had noted some persistent nasal obstruction. Visual acuity was 20/20 in each eye with normal pupils, and he had markedly injected conjunctiva with chemosis and brawny lid edema. His proptosis measured 29 mm in the right eye and 30 mm in the left eye. He had symmetrical but moderate reduction of ocular movements. His general health was otherwise good. B,C, axial and coronal computed tomography scans showed diffuse bilateral infiltration replacing orbital fat, obliterating other structures, and causing proptosis, with swelling in his inferior and middle turbinates. He had a biopsy performed of both the orbit and nasal passages. The orbital biopsy specimen showed dense sclerosing inflammation often with angiocentric concentration of a mixed infiltrate of lymphocytes, plasma cells, polymorphonuclear leukocytes, giant cells, and follicles (D, original magnification, x4; E, original magnification, x25). Immunohistochemistry was consistent with a polyclonal inflammatory disorder, and a diagnosis of nonspecific sclerosing inflammation was made. Biopsy specimen of the nasal tissue showed granulation tissue with a mixture of both acute and granulomatous infiltration. There was no evidence of fibrinoid necrosis of vessels, but a few focal microabscesses were noted. Although there was suspicion of Wegener granulomatosis, a definitive diagnosis could not be made. The patient was treated with oral prednisone starting at 40 mg daily and decreasing to 5 mg weekly. This was followed by orbital radiation of 2000 cOy in 10 treatments. This led to only partial resolution of his problems, and it was not possible for him to stop receiving steroids. By September 1987, his visual acuity was 20/15 in each eye, his proptosis had reduced to 22 mm in each eye, and his nasal passages had cleared. Immunosuppression was considered, but he decided to continue receiving 10 mg of prednisone daily. He gradually stopped treatment over the next 10 months. F, The patient at 8 months poststeroid treatment with much improvement. His ocular situation remained stable until 1991, when a nasal obstruction developed. Repeat computed tomography scan showed reduced proprosis but persistent obliteration of all fat planes. He remained clinically stable until November 1992, when he was seen for nasal obstruction, shortness of breath, and sore throat. Systemic investigation at that point showed bilateral, ill-defined densities in the chest, and he had a subglottic inflammatory mass, of which a biopsy was done, the results of which showed only chronic inflammation. At this point, his c-ANCA test result was positive and a definitive diagnosis of Wegener granulomatosis was made. He began receiving Septra and corticosteroids. Within 6 weeks, he stopped taking steroids; his breathing had improved because of decreased obstruction of his airway and nasal passages and reduction of the pulmonary infiltrates. He was last seen in April 1995 and was completely stable while taking Septra with no respiratory or orbital symproms. </p><p>clinical pattern and its correlation with the orbital, radio-logic, and histopathologic findings. Two patients pre-sented with diagnostic systemic features evident at an early stage in the orbital process; thus, orbital biopsy was not obtained. </p><p>Results </p><p>Presentation to the Referring Specialist The study group consisted of 5 males and 8 females com-prising 10 white patients, 2 American Indian patients, and 1 Asian patient. The average age at ophthalmic presenta-</p><p>Table 1. Main Ocular Features at First Ophthalmic Presentation </p><p>Main Ocular Features </p><p>Proptosis Bilateral proptosis Proptosis with scleritis </p><p>Reduced visual acuity Bilateral reduced vision Reduced vision and scleritis Reduced vision with mass White eye and no mass </p><p>Scleritis Bilateral scleritis Scleritis with proptosis </p><p>Ocular pain Facial pain </p><p>Ocular injection Lid features </p><p>No. </p><p>7/13 3/7 1/7 7/13 4/7 4/7 2/7 1/7 6/13 3/6 1/6 9/13 6/9 9/13 4/13 </p><p>tion was 44 years (range, 9 to 69 years), which is 2 years later than the first attributable symptoms (42 years). The average duration of follow-up was 30 months (range, 3 to 109 months). </p><p>The main features on first ophthalmic presentation are listed in Table 1. They differ from the disease encountered in follow-up in both site and severity of disease. The predominant initial reported symptoms were proptosis as-sociated with ocular or facial pain and a red eye in which scleritis was diagnosed earlier. The level of visual disabil-ity at presentation was usually moderate; in only one case was it reduced below 20/200 (in one eye of a woman who suffered a chronic red eye for 1 year before presentation). Disease at presentation was bilateral in six cases (Fig 1). </p><p>In all but two cases, ear, nose, and throat symptoms were active during the 3 months before ophthalmic pre-sentation (Table 2). Typical symptoms were plugged nose and ears, epistaxis or clear nasal discharge, pressure sen-sations in the ears or over the paranasal sinuses, draining ears, and hearing loss or tinnitus (Fig 2). Three of the patients had been treated symptomatically without a diag-nosis being made: one with antibiotics for radiologic eth-moiditis, one with sinus curettage (no biopsy) and antibi-</p><p>Table 2. Overview of Disease Progression: 13 Patients </p><p>Unilateral Bilateral ENT Systemic Disease Disease Features Features </p><p>At presentation 7 6 11 5 During follow-up 2 11 13 8 </p><p>ENT = ear, nose, and throat. </p><p>685 </p></li><li><p>Ophthalmology Volume 104, Number 4, April 1997 </p><p>Figure 2. A, computed tomography scan taken in 1987 of the inner ear showing bone erosion that was associated with drainage from the ear, hearing loss, and tinnitus. The patient had been referred with a 2-month history of progressive orbital cellulitis and infiltration treated as an infection. B,C, axial and coronal computed tomography scans. She had severe necrotizing scleritis and adjacent orbital infiltration on the left side, which was associated with clinically minimal scleritis on the right. There was an extensive choroidal and retinal detachment. Biopsy results of the orbit showed mixed inflammation with focal microabscesses consistent with features of Wegener granulomatosis. Systemic study results, however, were negative. The patient was treated with corticosteroids and cyclophosphamide, and both her ocular and ear, nose, and throat symptoms resolved, the left eye becoming phthisical. D, she was subsequently seen in June 1990 with some reported ear problems, but repeat computed tomography scans of the orbits and ears showed repair of the bone and no active disease. The patient's treatment consisted of prednisone 60 mg daily and cyclophosphamide 150 mg daily. The prednisone was reduced and discontinued over a 3-month period, and the patient stopped taking cyclophosphamide within 8 months. </p><p>otics, and one with local treatment for mastoiditis. Gum biopsy results before referral in one patient showed mixed inflammation suggesting WG, which was not pursued be-cause the gum growths resolved without treatment. Two other patients with long histories of nasal discomfort had undergone surgery in the past without diagnosis (eth-moidectomy 16 years previously and nasal surgery 10 years previously). </p><p>Systemic symptoms were seen in five patients at pre-sentation. Two patients had malaise and weight loss, and one patient experienced arthralgia. The final two had clini-cally active systemic disease: one with foot drop and chest crepitations associated with mild shadowing on X rays, and the other with multiple systemic problems including pneumonia, splenic infarct, congestive cardiac failure, and orbital inflammation with cranial nerve palsies. This latter was the only case not presenting primarily for ophthalmo-logic care. </p><p>686 </p><p>Evolution </p><p>The disease progressed with an increased number and severity of signs and symptoms as well as the individual inflammatory and mass effects summarized in Tables 2 and 3. All patients eventually showed ear, nose, and throat features. In three cases, these were limited to mild hearing deficits associated with mastoiditis. Although 6 of 10 had unilateral disease at presentation, ocular features became bilateral in all but 2 patients. </p><p>The findings formed three relatively distinct patterns: diffuse orbital involvement, lacrimal involvement, or midline involvement associated with visual deterioration. The globe was always displaced away from the causative orbital mass. Lid swelling with brawny discoloration was particularly prominent in those with lacrimal gland involvement (Figs 3 and 4). </p><p>An orbital mass developed in all patients in the series, </p></li><li><p>Perry et al . Wegener Granulomatosis of the Orbit </p><p>Table 3. Main Categories of Ophthalmic Disease Encountered during Follow-up </p><p>Symptom or Sign </p><p>Orbital mass Proptosis Eyelid swelling and injection Optic neuropathy Scleritis Keratitis Ocular restriction Uveitis </p><p>No. </p><p>13/13 11/13 8/13 8/13 6/13 6/13 4/13 3/13 </p><p>including those who presented initially with scleritis (6/ 13, 44%). Scleritis was usually described as nodular with necrosis and, by the time of consultation, was associated in all six patients with typical white, subepithelial, stro-mal, corneal infiltrates with a clear limbal zone (Figs SA and 5B). </p><p>Eight of the 13 patients lost visual acuity (total = 13 eyes) (Table 4). Nine eyes in five patients showed visual deterioration during ophthalmic evaluation; significantly, of those presenting with normal acuity, subsequent visual loss did not develop in any. Scleritis was the initial pre-sentation in four of the eight patients with visual loss. In all eight, there was an associated orbital mass (midline, apical, or diffuse on CT scan) that caused proptosis in all but one affected eye. Optic neuropathy was diagnosed in all eight patients. Progressive loss was documented by swollen or pale disc, decreased vision, or an associated relative afferent pupillary defect. One patient had a fulmi-nant course commencing with focal scleritis, progressive uveitis, retinal and choroidal detachments, and proptosis with restricted ocular movements. This developed into progressive, massive, necrotizing scleritis, panophthal-mitis, and adjacent orbital infiltration. The final vis...</p></li></ul>