Infliximab-Induced Optic Perineuritis and Facial Myositis

Optic neuritis is an inflammatory condition involving the optic nerve with autoimmune, demyelinating, toxic or infectious etiologies. Myositis is a rare but reported complication of infliximab (1), whereas the incidence of infliximab-induced optic neuritis is far more common than infliximab-induced myositis (1), occurring in approximately 10.4 per 100,000 person-years in a retrospective population-based cohort study (2).

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Infliximab-Induced Optic Perineuritis and Facial Myositis Loulwah Mukharesh, MD, Amanda Tinsley, MD O ptic neuritis is an inflammatory condition involving the optic nerve with autoimmune, demyelinating, toxic or infectious etiologies. Myositis is a rare but reported complication of infliximab (1), whereas the incidence of infliximab-induced optic neuritis is far more common than infliximab-induced myositis (1), occurring in approximately 10.4 per 100,000 person-years in a retrospective population-based cohort study (2). Infliximab is a monoclonal antibody that inhibits tumor necrosis factor alpha (TNF-a) and thereby shifts the balance between cellmediated immunity and humoral-based immunity, which may lead to the development of other known autoimmune diseases in individual patients (1,3). With the current expansion of immune-based therapies, it is imperative to remain vigilant to the potential development of new autoimmune diseases (4,5). This is essential to discontinue the possible offending agent. Although optic perineuritis and more rarely polymyositis are possible adverse events of infliximab use, we report a unique presentation of optic neuritis in combination with facial myositis involving the lateral pterygoid muscle in a patient taking infliximab for an unspecified rheumatologic disease. CASE REPORT We report a 31-year-old African American woman with an extensive rheumatologic history on infliximab for 6 months, who presented with acute onset of visual disturbance in the right eye and right-sided headaches for 2 days. She described her vision as “brightening white spots” in the right eye that progressed to a central spiral-shaped scotoma with painful eye movements. Her medical history included an unspecified systemic inflammatory disorder characterized by sclerotic bone lesions of the pelvis including the sacroiliac joints, nongranulomatous anterior uveitis, and diffuse lymphadenopathy (mediastinal, paratracheal, mesenteric, retroperitoneal, external iliac, and inguinal) identified by full-body comDepartment of Neuro-Ophthalmology (LM), Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; and Department of Neurology (LM, AT), George Washington University, Washington, DC. The authors report no conflicts of interest. L. Mukharesh: literature review and manuscript writing. A. Tinsley: concept analysis and critical revision of the article. Address correspondence to Loulwah Mukharesh, MD; E-mail: [e-mail] Mukharesh and Tinsley: J Neuro-Ophthalmol 2022; 42: e583-e585 puterized tomography scan and positron emission tomography scan imaging. Biopsies of the right inguinal lymph node, bone marrow, and left iliac bone returned negative for sarcoidosis or other immunological etiologies, infections, or malignancies. She was started on infliximab as an off-label treatment, with adequate control of her rheumatologic disease. Examination demonstrated a decreased visual acuity of 20/CF (counting fingers) with dyschromatopsia and a relative afferent pupillary defect in the right eye and an otherwise unremarkable ophthalmic and neurological examination. Her right temple and jaw were tender to palpation. Brain MRI with and without contrast was normal. However, her orbit/face/neck MRI with and without contrast revealed increased T2 hyperintense signal and enhancement of the right optic nerve sheath and T2 hyperintense signal of the right lateral pterygoid muscle in the face (Fig. 1). Cerebrospinal fluid analysis revealed the following: white blood cell count 0, red blood cell count 0, glucose 51 mg/dL (normal 45–80 mg/dL), total protein 25 mg/dL (normal 15–60 mg/dL), normal IgG index levels, an elevated myelin basic protein level of 2.3 ng/mL (normal 0– 1.2 ng/mL), positive type 4 oligoclonal bands, and a negative CSF infectious panel. Serum aquaporin-4 IgG (AQP4) antibody and other multiple sclerosis mimics including a complete rheumatological and infectious panel were negative except elevated CRP 34.0 mg/L (normal 0.0–4.9) and ESR 34 mm/hour (normal 0–32). Myelin oligodendrocyte glycoprotein (MOG) antibody testing was not routinely tested for or available at that time. Optical coherence tomography (OCT) showed no thinning, edema, or asymmetry of the retinal nerve fiber layers (RNFL) bilaterally (average thickness 108 mm in the right eye; 106 mm in the left eye). The patient was admitted to the hospital, where she received 1 g of intravenous methylprednisolone for 3 days that led to a marked improvement in her vision, right eye pain, and right facial pain. Her visual acuity improved to 20/25 in the right eye and remained 20/20 in the left eye. Infliximab was immediately discontinued because of concern for this medication being the culprit for her symptoms. She was discharged on 60 mg of oral prednisone that was tapered over 8 weeks and was transitioned to oral methotrexate as a steroid-sparing agent to keep her unspecified rheumatologic disease in remission. After 3 months of initial presentation, her visual acuity returned to baseline of 20/20 in the right eye, remained stable at 20/20 e583 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. T2 axial magnetic resonance image shows hyperintensity and inflammation of the right lateral pterygoid muscle (arrow). B. Postcontrast T1 coronal magnetic resonance image of the orbits shows peripheral enhancement of the right optic nerve sheath (arrow). in the left eye, with 50% red desaturation and a relative afferent pupillary defect in the right eye, whereas her fundus examination showed subtle optic nerves in both eyes with subtle temporal pallor in the right eye. A repeat OCT at that time showed slight borderline superior temporal thinning of the RNFL (average thickness was 73 mm) on the right and normal thickness on the left, which overall remained stable after one year. Eighteen months after initial presentation, she remained off infliximab without development of new neurological or visual symptoms. She experienced intermittent but improved mild right facial pain that was later shown to be early osteoarthritis of the right temporomandibular joint using MRI. The etiology of which remained unclear but perhaps secondary to her previous episode of facial myositis. She has not followed up in the neurology clinic since noting improvement in her symptoms. DISCUSSION Infliximab is a chimeric monoclonal antibody that inhibits TNF-a and is a highly effective treatment used for many different autoimmune diseases, such as rheumatoid arthritis, Crohn’s disease, psoriasis, and ankylosing spondylitis. However, paradoxically, TNF-a inhibitors, such as infliximab, have also been associated with the rare development of de novo systemic autoimmune diseases, such as lupus and vasculitis (1), or neurological autoimmune diseases, such as optic neuritis, transverse myelitis, and neuromuscular syndromes such as Guillain–Barre syndrome (3). Although the incidence of optic neuritis in patients using TNF-a inhibitors was 10.4 (95% confidence interval 3.3– 32.2) cases per 100,000 person-years in a retrospective population-based cohort study (2), there have only been case reports describing polymyositis or dermatomyositis in association with TNF-a agents (1,3). To the best of our knowledge, there have been no case reports describing a combination of inflammation of a facial muscle with or e584 without involvement of the optic nerve in the setting of TNF-a use. It remains unclear how TNF-a medications can treat certain autoimmune diseases while inducing others, but several theories exist on the mechanism of triggering or unmasking immunemediated diseases such as altering the balance between the T-cell subsets by shifting the immune response from a cell-mediated immunity (TH1) to humoral immunity (TH2) (1,3). The upregulation of TH2-mediated immune response may lead to the stimulation of B-cell–mediated interactions, whereas autoreactive B-cells escape surveillance by the inhibition of T-cytotoxic lymphocytes and T regulatory cells (3). Furthermore, targeted immunotherapies such as immune checkpoint modulators have been shown to be effective cancer treatments but have also been associated with autoimmunerelated adverse events such as myasthenia gravis, Guillain– Barre syndrome, autoimmune thyroid diseases, and other neurologic or systemic autoimmune diseases (4,5). Given that we are currently living in an exciting era of an ever-expanding list of immunologic therapies that treat numerous conditions including autoimmune diseases and malignancies, it is important to stay vigilant that these medications can also potentially lead to other autoimmune diseases through immune modulation. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. Mukharesh and A. Tinsley; b. Acquisition of data: L. Mukharesh and A. Tinsley; c. Analysis and interpretation of data: L. Mukharesh and A. Tinsley. Category 2: a. Drafting the manuscript: L. Mukharesh; b. Revising it for intellectual content: A. Tinsley. Category 3: a. Final approval of the completed manuscript: L. Mukharesh and A. Tinsley. ACKNOWLEDGMENTS Dr L. Mukharesh is a clinical fellow at the Division of Neuro-ophthalmology in the Department of Mukharesh and Tinsley: J Neuro-Ophthalmol 2022; 42: e583-e585 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Ophthalmology at Massachusetts Eye and Ear Infirmary, Harvard Medical School. Dr. A. Tinsley is an Assistant Professor at the Department of Neurology at George Washington University, who is also the Director of the Headache Center and has a special interest in patients with neuro-immunological diseases. REFERENCES 1. Zhou Y, Lower EE, Li H, Baughman RP. 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Semin Ophthalmol. 2021;36:241– 249. e585 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.