Recurrent Optic Perineuritis as the First Manifestation of Relapsing Polychondritis

Clinical Correspondence Recurrent Optic Perineuritis as the First Manifestation of Relapsing Polychondritis Yusaku Miura, MD, Ken Fukuda, MD, PhD, Yoshinori Taniguchi, MD, PhD, Masahiro Komori, MD, PhD, Atsuki Fukushima, MD, PhD R elapsing polychondritis (RP) is a rare, chronic, systemic inflammatory disorder of cartilaginous structures such as the ears, nose, larynx, trachea, joints, heart, skin, and eyes and is potentially fatal (1,2). Various ocular manifestations —including episcleritis or scleritis (23%–47%), conjunctivitis (5%–35%), iridocyclitis (3%–26%), and keratitis (9%–10%)—have been found to occur in up to 65% of patients (1–4). Optic perineuritis is also a rare inflammatory disorder of the optic nerve sheath and occurs as idiopathic or secondary to systemic inflammatory diseases. The causes of secondary optic perineuritis are syphilis, sarcoidosis, Behcet disease, Crohn disease, and granulomatosis with polyangiitis. Optic perineuritis, however, has not previously been associated with RP. A 74-year-old Japanese woman was referred to our hospital with complaints of vision loss and orbital pain in the left eye. Best-corrected visual acuity (BCVA) in the left eye was 20/60, and the left eye visual field showed paracentral scotoma. Ophthalmoscopy revealed only slight cataract bilaterally. Critical flicker frequency was 36 Hz for the right eye and 25 Hz for the left eye; a left afferent pupillary defect (APD) was present. Laboratory studies revealed that anti–aquaporin 4 antibody titer, anti–myelin oligodendrocyte glycoprotein antibody titer, rapid plasma reagin for syphilis, Treponema pallidum antibody testing, angiotensin-converting enzyme, leukocyte count, erythrocyte sedimentation rate, and C-reactive protein level were within normal limits. Gadolinium-enhanced T1-weighted MRI with fat-suppression showed a high signal intensity around the left optic nerve (“tram-track” on axial views), leading to a diagnosis of left optic perineuritis (Fig. 1). The left eye BCVA recovered to 20/30 after intravenous methylprednisolone therapy (IVMP: 1 g/day for 3 consecutive days) and oral prednisolone therapy for 2 weeks. Three months later, the patient was again referred to us with complaints of vision loss and orbital pain, this time in her right eye. BCVA was 20/50 in the right eye and 20/25 in the left eye. The right eye visual field showed an enlarged blind spot, and sensitivity of the central visual field was reduced. Ophthalmoscopy and hematologic analysis did not reveal any abnormalities. An APD was present in the right eye. Gadolinium-enhanced T1-weighted MRI with fatsuppression showed enhancement around the right optic nerve, and right optic perineuritis was diagnosed. The right eye BCVA recovered to 20/25 after treatment with IVMP and oral prednisolone for 2 weeks. One month later, she was referred to us with complaints of recurrent vision loss and orbital pain in her right eye. BCVA was 20/60 in the right eye and 20/30 in the left eye. Ophthalmoscopy and hematologic analysis again showed no remarkable findings. An APD was apparent in the right eye. In contrast to previous episodes, the patient’s right ear was swollen and red (Fig. 2A, B). Gadolinium-enhanced T1-weighted MRI with fatsuppression showed enhancement around the right optic nerve, whereas diffusion-weighted MRI showed a high signal intensity in the right auricle (Fig. 2C). Ultrasonography of the right auricle showed the increased power Doppler signals. Histological analysis of a punch biopsy specimen from the right auricle revealed perichondritis with the presence of lymphocytes and polymorphonuclear Departments of Ophthalmology and Visual Science (YM, KF, AF), Endocrinology, Metabolism, and Nephrology (YT), and Otolaryngology (MK), Kochi Medical School, Kochi University, Nankoku City, 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]. Miura et al: J Neuro-Ophthalmol 2019; 39: 513-514 FIG. 1. MRI. Gadolinium-enhanced T1-weighted MRI with fat-suppression demonstrating left optic nerve sheath “tram-track” enhancement. 513 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Auricular inflammation. The left auricle was normal (A), whereas the right auricle was swollen and red (B). Diffusionweighted MRI showed a high signal intensity (arrowhead) in the right auricle (C). Histological analysis of right auricular tissue stained with hematoxylin-eosin revealed perichondritis with the presence of lymphocytes and polymorphonuclear leukocytes (D). Scale bar = 100 mm. leukocytes (Fig. 2D)—namely, auricular chondritis. The patient was diagnosed with recurrent optic perineuritis due to RP, in accordance with the criteria of Damiani and Levine (5). Her right BCVA improved to 20/20 and her right ear returned to normal after IVMP. Oral prednisolone therapy was then started at a daily dose that gradually declined from 30 to 2.5 mg/day over 12 weeks. Right optic perineuritis recurred at the dose of 2.5 mg/day, and her symptoms improved after increasing the dose to 20 mg. To prevent recurrence of optic perineuritis during subsequent tapering of prednisolone, we added oral methotrexate (6 mg/week) to her regimen at a prednisolone dose of 5 mg. After the addition of methotrexate, prednisolone was tapered and discontinued. There has been no recurrence to date during the subsequent 2 and a half years. As far as we are aware, this is a first reported case of RP manifesting as optic perineuritis before inflammation in any other organ. Given the life-threatening potential of this disorder, early diagnosis and intervention are crucial for a good prognosis. RP is a systemic autoimmune disease characterized by inflammation of cartilage and collagencontaining tissues throughout the body. The most common manifestation of RP is auricular chondritis, which occurs in over 80% of patients. The ocular manifestations in RP commonly include episcleritis/scleritis, conjunctivitis, iridocyclitis, and keratitis. Our report reveals that the optic nerve sheath may be the initial target of RP, with optic perineuritis being a marker of disease severity. Optic perineuritis responds well to anti-inflammatory or corticosteroid therapy, but relapse after brief treatment is common. Although there is no established treatment protocols for RP, many patients require immunosuppressive agents together with systemic corticosteroids. Our patient 514 also required the addition of methotrexate during steroid tapering to prevent the relapse of optic perineuritis. McAdam’s or Damiani’s criteria used for the diagnosis of RP are mainly based on clinical findings. RP may thus be difficult to diagnose in its early stages. Although optic perineuritis is not a common manifestation in patients with RP, physicians should be aware that RP can be a cause of recurrent steroid-responsive optic perineuritis. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Yusaku Miura, Ken Fukuda, and Atsuki Fukushima; b. Acquisition of data: Yusaku Miura, Ken Fukuda, Yoshinori Taniguchi, and Masahiro Komori; c. Analysis and interpretation of data: Yusaku Miura and Ken Fukuda. Category 2: a. Drafting the manuscript: Yusaku Miura, Ken Fukuda, and Atsuki Fukushima; b. Revising it for intellectual content: Yusaku Miura, Ken Fukuda, and Atsuki Fukushima. Category 3: a. Final approval of the completed manuscript: Yusaku Miura, Ken Fukuda, Yoshinori Taniguchi, Masahiro Komori, and Atsuki Fukushima. REFERENCES 1. McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine (Baltimore). 1976;55:193– 215. 2. Zeuner M, Straub RH, Rauh G, Albert ED, Scholmerich J, Lang B. Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients. J Rheumatol. 1997;24:96–101. 3. Isaak BL, Liesegang TJ, Michet CJ Jr. Ocular and systemic findings in relapsing polychondritis. Ophthalmology. 1986;93:681–689. 4. 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