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Show f. Clin. Neuro-ophthalmol. 3: 163-168, 1983. Extraocular Muscle Involvement in Wegener's Granulomatosis BARRY S. PINCHOFF, M.D. DAVID A. SPAHLINGER, M.D. TERRY J. BERGSTROM, M.D. GARY S. SANDALL, M.D. Abstract A 44-year-old man with Wegener's granulomatosis involving the upper and lower respiratory tracts developed a diplopia with involvement of three extraocular muscles of one eye and one extraocular muscle of the other eye. The ocular and orbital examinations were otherwise normal, as were computerized tomography (CT) scans of the brain and orbits. The patient was treated with systemic Cytoxan and Prednisone and the respiratory and extraocular muscle abnormalities cleared within 1 month. Because of the bilateral extraocular muscle involvement, the absence of central nervous system or orbital findings, and the rapid and complete resolution after Cytoxan and Prednisone therapy, a diffuse vasculitis affecting the extraocular muscles was implicated as the etiology of the diplopia. In 1936, Wegener) described a small number of patients with necrotizing granulomatous vasculitis involving the upper and lower respiratory tracts and kidneys. Wegener's granulomatosis has been subsequently identified as a systemic disease; and involvement of the eye, ear, paranasal sinuses, skin, joints, nervous system, and cardiovascular system are well-recognized.~·:1Eye involvement can be one of the initial manifestations of Wegener's granulomatosis, and ocular findings occur in a large proportion of patients (up to 50%) with the generalized disease.~· 4. ". Ii Many different ocular manifestations have been reported previously, including conjunctivitis, scleritis, corneoscleraI ulceration, uveitis, optic neuropathy, retinal artery occlusions, central retinal artery occlusion, nasolacrimal obstruction, and orbital involvement with subsequent proptosis and limitation of movement of the globe." We present a case of Wegener's granulomatosis with acute onset of diplopia and extraocular muscle involvement without any other ocular or orbital findings. From the Departments of Ophthalmology (B5P, TjB, G55), and Medicine (DA5). University of Michigan Hospitals, Ann Arbor, Michigan. September 1983 Case Report A 44-year-old male was referred for admission to the University of Michigan Hospitals with a severe sinusitis and the recent onset of diplopia. Six months prior to admission, the patient had developed a serous otitis media followed by rhinorrhea and frontal headaches. At that time antibiotics and decongestants were unsuccessful and a left myringotomy had to be performed. At 3 months prior to admission, he noticed anorexia, fatigue, night sweats, and symptoms of sinusitis. Bilateral nasoantral windows were created in order to treat the sinusitis. Histopathological examination of the specimens from that procedure revealed granulomata and vasculitis (Fig. 1). At admission the patient was ill-appearing and in moderate distress. His oral temperature was lO2°F, respiratory rate was 24, and pulse was 104. Laboratory examination revealed the following abnormalities: Westegren sedimentation rate of 122; rheumatoid factor positive at a dilution of 1:640; alkaline phosphatase of 350 I.U./liter; and a marked microscopic hematuria. Spinal fluid evaluation was normal. The fluid was clear in color, no cells were present, and glucose and protein levels were 61 mg/dl and 20 mg/dl, respectively. Although the lungs were clear to auscultation and percussion, radiographic examination revealed bilateral nodular infiltrates of the lungs (Fig. 2a). Computerized tomography (CT) scans of the sinuses, orbits, base of skull, and brain were normal (Fig.3). On the second hospital day, the patient was evaluated for his diplopia in the Department of Ophthalmology. The motility examination revealed an esotropia of 3 diopters at distance and 12 diopters at near in the straight ahead position. In right gaze, he had an exotropia of 14 diopters and In left gaze he had an esotropia of 30 diopters with a left hypotropia of 4 diopters. In upgaze his left hypotropia was 12 diopters, and in downgaze he had an esotropia of 14 diopters (Fig. 4). On duction testing there was a lag of elevation, abduction and adduction of the left eye, and a mild lag 163 Wegener's Granulomatosis Figure 1. Tissue from maxillary sinus demonstrates granulomas (white arrows) and lymphocytic infiltration of media of artery (black arrow) on elastin stain preparation. of abduction of the right eye. Testing of the oblique muscles function with head tilting to the right and left revealed no abnormalities (Fig. 4); and there was no cyclotorsion on double Maddox rod testing. The remainder of the ocular exam was normal with no evidence of proptosis, resistance to retropulsion, ptosis, pupil abnormalities, uveitis, keratitis, conjunctivitis, or optic nerve involvement. After 11 days of therapy with Prednisone (60 mg daily) and Cytoxan (100 mg daily), a repeat ocular examination was performed. The patient was now orthophoric at distance in (he straight ahead position; in right gaze he had an esotropia of 4 diopters and in left gaze an esotropia of 16 diopters (Fig. 5). There was no residual left hypotropia. There was a mild lag of abduction of the left eye. At near he had an esotropia of 18 diopters in the straight ahead position. The remaindE'r of the ocular exam was normal, as before. One month later the patient was orthophoric at distance (Fig. 6) with 2 diopters of exophoria at near. There were no significant differences in right, left, up-, or downgaze. Convergence and divergence amplitudes were normal. The remainder of the ocular exam was within normal limits. The patient also had resolution of his systemic symp-toms and clearing of his pulmonary infiltrates (Fig. 2b) and of his hematuria. Discussion Although Wegener's granulomatosis was first described by Klinger in 1931 7 and defined clearly as a distinct clinical and pathologic entity a few years later by Wegener,~'"the true incidence of the disease is not known. It occurs more frequently in males and in the fifth decade of life (although it can occur at almost any age). The etiology of this disease also remains unknown, although a hypersensitivity reaction to an unidentified antigen has been implicated because of the upper airway involvement.: l There are, however, no definable geographic, occupational, or allergic associations. Clinically, most patients present with rhinorrhea, sinusitis, and serous otitis media. Pulmonary involvement is usually associated with complaints of chest pain, cough, dyspnea, and occasional hemoptysis, although some patients (as did our patient) remain asymptomatic despite abnormal chest radiographs. Renal involvement with focal, necrotizing glomerulitis is present in the generalized form of the disease and, prior to Cytoxan therapy, rapidly progressed to end-stage renal disease.~' 4 Journal of Clinical Neuro-ophthalmology Pinchoff, Spahlinger, Bergstrom, Sandall Figures 2a and 2b. (a) Chest x-ray shows multiple lesions in both lung fields, particularly in the hilar areas, upon admission. (b) Repeat chest x-ray shows resolution of pulmonarv lesions 1 month after initiation of therapy. Involvement of the nervous and neuromuscular systems may occur in more than half of the cases and may be caused by granulomatous lesions encroaching upon the nervous system by contiguous invasion from nasal or paranasal granulomas, by granulomatous lesions remote from the nasal granuloma, or by vasculitis involving the nervous system. 9 Nonocular myopathies have also been reported. 9 Proptosis is the most common ocular manifestation, occurring in 22% of the patients, and fol- September 1983 lowed in frequency by conjunctival, episcleral and scleral inflammation, and optic nerve involvement; uveitis, retinal artery occlusion, and lacrimal obstruction are less common," Extraocular motility disturbances have been reported in Wegener's granulomatosis as a complication of contiguous spread to the orbits from necrotizing granulomatous lesions of the upper respiratory tracts. However, the random pattern of isolated extraocular muscle involvement of both eyes in the presence of otherwise normal ocular, 165 j Wegener's Granulomatosis Figure 3. Representative axial computed tomographic scan does not show any evidence of orbital masses or abnormalities. 12 a. L HYPOTROPIA 1 14 a. XT 3 a. ET -----+ 30 a. ET 4 a. LEFT HYPOTROPIA 14 a. ET r-HEAD TILT~ 8a.ET Sa.ET 4 a. RH Figure 4. Extraocular muscle measurements at 6 meters at the time of the initial evaluation. 1 a. E I 4 a. ET t-(--- ORTHOPHORIA ---t 16 a. ET j 1 a. RH Figure 5. Extraocular muscle measurements at 6 meters on 12th hospital day (11 days after initiation of therapy). Journal of Clinical Neuro-ophthalmology Pinchoff, Spahlinger, Bergstrom, Sandall l~X 1 ORTHOPHORIA~ ORTHOPHORIA ----4 ORTHOPHORIA ! 1 ~ E Figure 6. Extraocular muscle measurements at 6 meters after 6 weeks of therapy. orbital, and CT examinations as in our case, has not (to our knowledge) been reported as yet. The histopathologic studies in Wegener's granulomatosis show a generalized focal necrotizing vasculitis affecting small- and medium-size arteries and veins 2 . 9 Small vessel vasculitis has been implicated as a cause of conjunctivitis, episcleritis, and scleritis; and focal vasculitis, possibly associated with occlusion of the anterior ciliary arteries, has been reported to cause localized or ring-shaped limbal ulcerations.5 . 10 Granulomatous vasculitis has the potential to involve any orbital structure including the optic nerve, optic vessels, and extraocular muscles; and vasculitis of the vasa vasorum and/or the posterior ciliary arteries (producing ischemic optic neuropathy) and vasculitis of the retinal arteries (producing ischemia of the inner retinal layers) have been reported.5 . Ii While corticosteroids produce clinical improvement, they do not alter the course of the disease. II However, the use of Cytoxan has made Wegener's granulomatosis virtually a curable disease with a greater than 90% remission rate.~· l~ The random pattern of isolated extraocular muscle involvement of both eyes of this patient in the presence of an otherwise normal ocular, orbital, and CT examination, along with a rapid and complete resolution on Cytoxan (cyclophosphamide) and Prednisone implicates a diffuse vasculitis as the etiology of this patient's diplopia. As mentioned previously, nonocular myopathies have been reported in Wegener's granulomatosis, but the biopsy reports in those patients have described not only a characteristic focal necrotizing arteritis, but also marked myopathic changes.9 These severe myopathic changes would not be expected to resolve so quickly and completely after therapy with steroids and cyclophosphamide and, therefore, were probably not the cause of the extraocular muscle involvement in this patient. Because of the random involvement of the extraocular muscles-left lateral rectus, left medial rectus, left superior rectus, and right lateral rectuscranial nerve involvement was not considered as a likely etiology for his diplopia, although cranial nerves are reported to have been "injured" by the September 1983 granulomas and vasculitis of Wegener's granulomatosis. 9 Therefore, the generalized focal necrotizing vasculitis of Wegener's granulomatosis can cause not only conjunctivitis, episcleritis, scleritis, limbal ulceration, central retinal artery occlusion, and retinal arteriole occlusions, but may also cause a random pattern of extraocular muscle abnormalities in the presence of an otherwise normal ocular and orbital examination. Using Cytoxan and Prednisone therapy, these vasculitides involving the extraocular muscles in Wegener's granulomatosis can be treated effectively with rapid and complete resolution. References 1. Wegener, F.: Uber generalisierte, septische Gefaesserkrankungen. Verh. Dtsch. Ges. Pathol. 29: 202210, 1936. 2. Fauci, AS, and Wolff, S.M.: Wegener's granulomatosis: Studies in 18 patients and a review of the literature. Medicine 52: 535-561, 1973. 3. Fauci, AS, Haynes B.F., and Katz, P.: The spectrum of vasculitis: Clinical pathologic, immunologic, and therapeutic considerations. Ann. Intern. Med. 89: 660-676, 1978. 4. Hoekstra, 1.A., and Fauci, AS: The granulomatous vasculitides. Clin. Rheum. Dis. 6: 373-387, 1980. 5. Haynes, B.F., Fishman, M.L., Fauci, AS, and Wolff, S.M.: The ocular manifestations of Wegener's granulomatosis. Am.]. Med. 63: 131-141, 1977. 6. Coutu, R.E., et al.: Limited form of vVegener's granulomatosis. Eye involvement as a major sign. ].A.M.A. 233: 868-871, 1975 7. Klinger, H.: Grenzformen der periarteritis nodosa. Frankfurt Z. Pathol. 42: 455-480,1931. 8. Wegener, F.: Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Beitr. Pilthol. 102: 36-68, 1939. 9. Drachman, D.A.: Neurological complications of Wegener's granulomatosis. Arch. Neurol. 8: 145-153, 1963. 10. Frayer, W.e.: The histopathology of perilimbal ulceration in Wegener's granulomatosis. Arch. OphthalmoI. 64: 58-64, 1960. 167 Wegener's Granulomatosis 1I. Hollander, D., and Manning, R.T.: The use of alkylating agents in the treatment of Wegener's granulomatosis. Ann. Intern. Med. 67: 393-398. 1967. 12. Reza, M.J., Dornfeld, L., Goldberg, L., et 031.: Wegener's granulomatosis. long-term follow-up of pa-tients treated with cyclophosphamide. Arthritis Rheum. 18: 501-506, 1975. Write for reprints to: Terry J. Bergstrom, M.D., Department of Ophthalmology, University of Michigan Hospitals, Ann Arbor, Michigan 48109. Journal of Clinical Neuro-ophthalmology |
