Postinfectious Optic Neuritis After Hand-Foot-Mouth Disease

A 33-year-old man presented with acute painless loss of vision in his right eye after hand-foot-mouth disease (HFMD). Examination confirmed a right optic neuropathy. Neuroimaging and routine evaluations for alternative causes for an optic neuropathy were negative. He was treated with high dose corticosteroids and made an almost complete visual recovery. Postinfectious optic neuritis has been reported after a vast array of infections including: varicella zoster virus, influenza virus, herpes simplex virus, Epstein-Barr Virus, Lyme disease, and many others. Although Coxsackie virus infections are a known cause of HFMD and have been reported to cause maculopathy, to the best of our knowledge, this is the first reported case of optic neuritis after HFMD in the English language ophthalmic literature.

Photo and Video Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Postinfectious Optic Neuritis After Hand–Foot–Mouth Disease Spencer C. Barrett, BS, Nita N. Bhat, MD, Shruthi H. Bindiganavile, MD, Andrew G. Lee, MD FIG. 1. External photographs showing multifocal erythematous macules involving the hands (A) and feet (B). Abstract: A 33-year-old man presented with acute painless loss of vision in his right eye after hand–foot–mouth disease (HFMD). Examination confirmed a right optic neuropathy. Neuroimaging and routine evaluations for alternative causes for an optic neuropathy were negative. He was treated with high dose corticosteroids and made an almost complete visual recovery. Postinfectious optic neuritis has been reported after a vast array of infections including: varicella zoster virus, influenza virus, herpes simplex virus, Epstein– Barr Virus, Lyme disease, and many others. Although Coxsackie virus infections are a known cause of HFMD and Department of Ophthalmology, Baylor College of Medicine (SCB, AGL), Houston, Texas; Department of Ophthalmology (NB, SHB, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Ophthalmology, The Houston Methodist Research Institute (AGL), Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology, MD Anderson Cancer Center (AGL), University of Texas, Houston, Texas; Department of Ophthalmology, Texas A and M College of Medicine (AGL), Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street Suite 450, Houston, TX 77030; E-mail: [e-mail] Barrett et al: J Neuro-Ophthalmol 2021; 41: e351-e353 have been reported to cause maculopathy, to the best of our knowledge, this is the first reported case of optic neuritis after HFMD in the English language ophthalmic literature. Journal of Neuro-Ophthalmology 2021;41:e351–353 doi: 10.1097/WNO.0000000000001163 © 2020 by North American Neuro-Ophthalmology Society A 33-year-old previously healthy man presented with a 2 days history of acute painless vision loss in his right eye. The medical history was significant for migraine and sinusitis. The remainder of his surgical, medical, ocular, family, and social history were noncontributory. Three weeks before presentation, he had crops of multifocal erythematous macules involving the hands, feet, and buccal mucosa, which the patient was able to confirm by presenting images he had taken during that time (Fig. 1). His medications included previous oral prednisone as empiric treatment of his “sinusitis.” He was subsequently diagnosed with hand–foot– mouth disease (HFMD) and admitted to the hospital. On examination, his visual acuity was 20 of 70 in the right eye and 20 of 20 in his left eye. There was a relative e351 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay FIG. 2. Fundus photographs showing sector pallor in the right eye and a normal optic nerve in the left eye. FIG. 3. Automated visual field testing showing a small paracentral depression in the right eye and nonspecific scatter in the left eye. afferent pupillary defect (RAPD) in the right eye. Slit-lamp biomicroscopic, motility, and intraocular pressure examinations were normal. Visual fields were evaluated at bedside with confrontational field testing and revealed a central depression in the right eye and normal in the left eye. Dilated fundus examination was normal with no optic disc edema or atrophy. There was no evidence of vitreous cell, vasculitis, or maculopathy. MRI of the head and orbit was normal and showed no enhancement of the optic nerve or demyelinating lesions. MRI of the cervical spine also showed no demyelinating lesions. Lumbar puncture showed normal opening pressure and cerebrospinal fluid composition, and notably showed no oligoclonal bands, which lowered suspicion for multiple sclerosis. Laboratory studies including erythrocyte sedimentation rate, C- reactive protein, thyroid studies, lysozyme, Bartonella titers, vitamin B12, folate, syphilis serology, aquaporin-4 (neuromyelitis antibody), myelin oligodendrocytic glycoprotein antibody, antinuclear antibody, rheumatoid factor, Sjogren syndrome antibodies, serum protein electrophoresis, QuantiFERON test for tuberculosis, Lyme disease, and Cryptococcus were all negative. Viral polymerase chain reaction testing for Coxsackie or other viral causes for HFMD was not performed. He was treated with intravenous methyl prednisolone followed by an oral taper. At 6-month follow-up, his vision had improved to 20/ 30 in the right eye. He had complete resolution of his skin and oral mucosal lesions of HFMD. He had a persistent right RAPD. There was now sector pallor and papillomacular bundle nerve fiber loss in the right eye. There was no subretinal fluid (Fig. 2). Automated visual field testing (HVF 24-2) showed a residual central depression with a mean deviation (MD) of 20.68 dB in the right eye and nonspecific scatter in the left eye (MD +0.34 dB) (Fig. 3). Optical coherence tomography showed sector retinal nerve fiber loss consistent with optic atrophy in the right eye (Fig. 4). FIG. 4. Optical coherence tomography showing retinal nerve fiber layer loss in the papillomacular bundle in the right eye. e352 Barrett et al: J Neuro-Ophthalmol 2021; 41: e351-e353 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay Most cases of optic neuritis (ON), especially those seen in adults, are idiopathic or are associated with multiple sclerosis (1). Postinfectious optic neuritis, however, especially in children can occur. In addition, one survey found that as many as 10% of ON patients had a preceding infectious disease leading up to their diagnosis and treatment (2). Although optic neuritis has been associated with a vast array of infectious diseases (e.g., varicella zoster virus, influenza virus, herpes simplex virus, Epstein–Barr Virus, cytomegalovirus, West Nile virus, HIV, syphilis, tuberculosis, Lyme disease, Bartonella, and Mycoplasma pneumonia) (1–7), to the best of our knowledge, this is the first case in the English language ophthalmic literature of optic neuritis due to HFMD in an adult. Although HFMD is most commonly associated with Coxsackie A Virus, Enterovirus 71 (EV71) is also considered a major pathogen in the development of this disease (8). This is of particular interest because EV71 has been more strongly associated with neurological findings during and after infection than Coxsackie A virus (8–10). The neurological findings that have been noted after EV71 infection include myoclonus, paralysis, encephalitis, meningitis, polio-like disease, and others (8–10). The pathophysiologic basis of postinfectious optic neuritis is inflammatory demyelination or inflammation of the optic nerve, which is mechanistically similar to acute multiple sclerosis flares. The specific mechanism (and target antigens) is unknown, but it is generally accepted that T-cell cytokine release and B-cell activation against myelin basic protein can be the driving force of inflammatory demyelination in patients with optic neuritis (11). Clinicians should be aware of postinfectious optic neuritis as a potential cause for acute optic neuritis. In the context of a known, recent infection, as in this patient who had an episode of HFMD 3 weeks before his presentation, an infectious disease work-up including lumbar puncture with cerebrospinal fluid testing (including viral etiologies) may be considered. It should also be noted that a normal MRI is a common finding in nondemyelinating optic neuritis, and this may be seen during the evaluation of a patient with a clinical image of optic neuritis. Furthermore, receiving steroid treatment for another indication, such as sinusitis, could also contribute to a normal MRI and should be considered during the work up. The authors believe that Barrett et al: J Neuro-Ophthalmol 2021; 41: e351-e353 HFMD should be added to the long list of potential postinfectious etiologies for acute optic neuritis. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee; b. Acquisition of data: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee; c. Analysis and interpretation of data: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee. Category 2: a. Drafting the manuscript: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee; b. Revising it for intellectual content: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: S. C. Barrett, N. Bhat, S. H. Bindiganavile, and A. G. Lee. REFERENCES 1. Kumar R, Bhargava A, Jaiswal G, Soni VR, Katbamna B, Vashisht A. A case of post encephalitic optic neuritis: clinical spectrum, differential diagnosis and management. J Ophthalmic Vis Res. 2018;13:191–194. 2. Choi DD, Park MS, Park KA. Incidence of optic neuritis in Korean children and adolescents: a nationwide survey and national registry analysis. J Neurol Sci. 2020;408:116554. 3. Povaliaeva DA, Egorov VV, Smoliakova GP, Danilova LP, Emanova LP, Zhajvoronok NS. Herpesviral infection as an etiological factor of acute idiopathic optic neuritis [in Russian]. Vestn Oftalmol. 2019;135:4–11. 4. Abel A, Mcclelland C, Lee MS. Critical review: typical and atypical optic neuritis. Surv Ophthalmol. 2019;64:770–779. 5. Nakamura M, Iwasaki Y, Takahashi T, Kaneko K, Nakashima I, Kunieda T, Kaneko S, Kusaka H. 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