Sequential Involvement of Oculomotor Nerve and Optic Nerve Sheath in Relapsing Polychondritis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Sequential Involvement of Oculomotor Nerve and Optic Nerve Sheath in Relapsing Polychondritis Toshihide Ikeda, MD, Takeshi Yoshida, MD, Hirotaka Yamamoto, MD, Masatsugu Hashida, MD, PhD, Kimiaki Urabe, MD, Chie Sotozono, MD, PhD, Ken Fukuda, MD, PhD R elapsing polychondritis (RP) is a chronic systemic inflammatory disorder of cartilaginous tissue. RP can affect the ears, nose, larynx, trachea, joints, heart, skin, and eyes and is potentially fatal. Moreover, its variety of systemic symptoms can be challenging for obtaining a correct diagnosis. Although more than 50% of patients with RP present with ocular manifestations such as episcleritis or scleritis, iridocyclitis, or keratitis at some stage of the disease (1), neuro-ophthalmological manifestations such as extraocular muscle palsy or optic neuritis are rare yet are potentially associated with serious disturbance of vision. We herein present a rare case of RP with oculomotor nerve palsy, optic perineuritis, scleritis, retinopathy, and nasal chondritis that was successfully treated with prompt initiation of systemic steroid therapy. A 71-year-old Japanese man developed progressive weakness, a frontal headache, and a fever at 1 month before initial presentation at Machida Hospital, Kochi-City, Kochi, Japan. On examination, he had elevated C-reactive protein (CRP), and computed tomography revealed swelling of the bilateral nasal mucosa. After a diagnosis of sinusitis by an otolaryngologist, a systemic antibiotics treatment was initiated. One week later, he presented at another hospital and underwent a neurological consultation because of progressive weakness, severe nasal tenderness, and the development of right ptosis and diplopia. No symptoms suggesting systemic vasculitis, including lung lesion, nephritis, or purpura, were observed. He was diagnosed with Guillain–Barré syndrome complicating right oculomotor nerve palsy and treated with intravenous immunoglobulin. He noted pain and hyperemia in his right eye during a follow-up at our hospital. BestMachida Hospital (TI, MH, KU), Kochi-City, Kochi, Japan; Department of Rheumatology (TY, HY), Chikamori Hospital, Kochi-City, Kochi, Japan; Department of Endocrinology, Metabolism, Nephrology and Rheumatology (HY), Kochi Medical School Hospital, Nankoku-City, Kochi, Japan; Department of Ophthalmology (CS), Kyoto Prefectural University of Medicine, Kyoto, Japan; and Department of Ophthalmology and Visual Science (KF), Kochi Medical School, Kochi University, Nankoku-City, Kochi, Japan. The authors report no conflicts of interest. Address correspondence to Ken Fukuda, MD, PhD, Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-City, Kochi 783-8505, Japan; E-mail: [e-mail] Ikeda et al: J Neuro-Ophthalmol 2022; 42: e497-e499 corrected visual acuity (BCVA) in both eyes was 20/25. Ophthalmoscopy revealed slight cataract bilaterally and diffuse anterior scleritis in the right eye (Fig. 1A–D). Bilateral retinal cotton-wool spots were observed (Fig. 1E, F), and impaired adduction in his right eye was observed. Betamethasone eye drop treatment was initiated for the scleritis, and improvement was noted within 1 week. One month later, he presented again complaining of left eye vision loss. His BCVA was 25/25 in the right eye and hand motion in the left eye, with extensive left visual field defects (Fig. 2A). Ophthalmoscopy revealed a relapse of scleritis in the right eye. Critical flicker frequency was 35 Hz in the right eye and unmeasurable in the left eye, and a relative afferent pupillary defect (RAPD) was present in his left eye. Fundus findings showed no redness or swelling in the optic disc in both eyes, and the bilateral retinal cottonwool spots had disappeared (Fig. 2B). Although there was no superficial temporal artery enlargement and tenderness, jaw claudication, or ear swelling/pain, he noted nasal tenderness. Because there were no significant abnormalities to explain the severe left eye visual impairment, immediate MRI of the orbit was performed. MRI showed high signal intensity around the left optic nerve on T1 fat-suppressed image with gadolinium enhancement (Fig. 2C, D), leading to a diagnosis of left optic perineuritis. Laboratory tests revealed an increased erythrocyte sedimentation rate (75 mm/h; normal, #10 mm/h), an elevated CRP level (1.25 mg/dL; normal, #0.14 mg/dL), and positive findings for antibodies to type II collagen (51.9 EU/mL; normal, ,20 EU/mL). Blood glucose test findings were within the normal limits, and the results of the serological tests for syphilis were negative. No bacteria or fungi were detected in the blood cultures, and no abnormal findings were found on echocardiography. Based on these findings, infective endocarditis was ruled out in this case. MPO-ANCA and PR-3-ANCA were negative. Pathological examination of a biopsy specimen of the nasal cartilage showed mild infiltration of lymphocytes and cartilage degeneration and fibrosis, so we made a diagnosis of RP in accordance with the clinical diagnostic criteria of Damiani et al (2). His left eye BCVA improved to 20/60 after intravenous methylprednisolone therapy (IVMP: 1 g/day for 3 e497 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Anterior and posterior ocular findings at initial presentation. Anterior and fundus imaging showed diffuse anterior scleritis in the patient’s right eye (A–D) and bilateral retinal cotton-wool spots (E, F). consecutive days), followed by oral prednisolone at a daily dose of 60 mg with gradual taper. After treatment, his left eye BCVA showed a remarkable improvement of 20/30 after 3 months and 20/25 after 9 months of treatment, and the slight central scotoma remaining after 2 weeks (Fig. 2E) had disappeared 1.5 months later (Fig. 2F) in the visual field test. We added oral methotrexate (6 mg/week) at a prednisolone dose of 30 mg/day yet discontinued it because of the appearance of liver dysfunction. To date, there has been no recurrence of ocular inflammation during the subsequent 11 months of maintenance therapy with oral prednisolone. Reportedly, ocular involvements occur in 50%–65% of patients with RP, with the common manifestations being scleritis, conjunctivitis, uveitis, and keratitis (1). Other rare ocular complications have also been reported, including extraocular muscle palsy, eyelid edema, proptosis, retinopathy, and optic neuritis. Our case developed uncommon RP ocu- lar manifestations, including oculomotor nerve palsy, retinopathy, and optic perineuritis in addition to the common complication of scleritis. To the best of our knowledge, this is the first report of this sequential development of rare neuro-ophthalmological manifestations such as oculomotor nerve palsy and optic perineuritis in a patient with RP. Although retinal cotton-wool spots are observed in various systemic diseases, diabetes, systemic infection, and autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, giant cell arteritis, and sarcoidosis were ruled out in this case. Given that kidney biopsy specimens of patients with RP have shown immunoglobulin and complement deposits, immune complex might also deposit in the retina. Early diagnosis and intervention by noticing these rare neuro-ophthalmological manifestations are paramount for a good prognosis because they are potentially sight threatening. RP is a recurrent and chronic autoimmune disease that FIG. 2. Ocular findings during follow-up examinations. At 1 month after initial presentation, Goldmann visual field testing revealed an extensive defect (A) and fundus imaging revealed a normal optic disc in the patient’s left eye (B). Gadoliniumenhanced T1-weighted MRI with fat suppression demonstrating left optic nerve sheath “tram-track” enhancement on axial views (C) and ring enhancement on the coronal view (D). Goldmann visual field testing of the left eye at 2 weeks (E) and 6 weeks (F) after treatment showed good recovery in response to steroid treatment. e498 Ikeda et al: J Neuro-Ophthalmol 2022; 42: e497-e499 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence specifically causes inflammation of various cartilage and collagen-containing tissues. Auricular chondritis is the most common manifestation of RP, and it occurs in more than 80% of the patients. Although, our patient did not have the typical symptom of auricular chondritis, various ocular involvements including scleritis, retinopathy, oculomotor nerve palsy, and optic perineuritis led to a diagnosis of RP. A case of RP presenting with oculomotor and abducens nerve palsies as the initial manifestation has been reported (3). We previously reported a case showing recurrent optic perineuritis as the first manifestation of relapsing polychondritis (4) and also reported a case of RP showing miscellaneous ocular symptoms including scleritis, conjunctivitis, eyelid edema, eye movement disorder, keratitis, and retinopathy (5). Although the lack of auricular inflammation kept us from diagnosing our case as RP at initial presentation, those various ocular manifestations lead us to suspect our case as RP based on our previous experience with RP cases (4,5). RP has extremely variable systemic symptoms and ocular manifestations, thus making a specific diagnosis of RP in its early stages difficult. Our case with RP accompanied by oculomotor nerve palsy and optic perineuritis suggests that RP should be considered in patients with these neuro-ophthalmological disorders so that they may be promptly diagnosed and treated. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T. Ikeda, T. Yoshida, and K. Fukuda; b. Acquisition of data: T. Ikeda, T. Yoshida, and H. Ikeda et al: J Neuro-Ophthalmol 2022; 42: e497-e499 Yamamoto; c. Analysis and interpretation of data: T. Ikeda, T. Yoshida, M. Hashida, K. Urabe, C. Sotozono, and K. Fukuda. Category 2: a. Drafting the manuscript: T. Ikeda, T. Yoshida, and K. Fukuda; b. Revising it for intellectual content: H. Yamamoto, M. Hashida, K. Urabe, and C. Sotozono. Category 3: a. Final approval of the completed manuscript: T. Ikeda, T. Yoshida, H. Yamamoto, M. Hashida, K. Urabe, C. Sotozono, and K. Fukuda. ACKNOWLEDGMENT The authors thank Dr. Yoshitaka Kumon, MD, PhD, Chikamori Hospital, for his insightful suggestions regarding patient care and the preparation of the manuscript. REFERENCES 1. Yoo JH, Chodosh J, Dana R. Relapsing polychondritis: systemic and ocular manifestations, differential diagnosis, management, and prognosis. Semin Ophthalmol. 2011;26:261–269. 2. Damiani JM, Levine HL. Relapsing polychondritis—report of ten cases. Laryngoscope. 1979;89:929–946. 3. Akiyama M, Kaneko Y, Hanaoka H, Kuwana M, Takeuchi T. Polychondritis presenting with oculomotor and abducens nerve palsies as the initial manifestation. Mod Rheumatol. 2016;26:790–793. 4. Miura Y, Fukuda K, Taniguchi Y, Komori M, Fukushima A. Recurrent optic perineuritis as the first manifestation of relapsing polychondritis. J Neuroophthalmol. 2019;39:513– 514. 5. Fukuda K, Kishimoto T, Fukushima A. Miscellaneous ocular symptoms in a case of relapsing polychondritis. Ocul Immunol Inflamm. 2021;29:352–354. e499 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.