with bilateral optic neuritis following influenza vaccination. The patient ... Therefore, annual immunization programs especially targeting .... Anthrax vaccination.
AUTHOR’S QUERY SHEET Author(s): F. U. Tan et al. Article title: Article no: NOPH 473106 Dear Author The following queries have arisen during the editing of your manuscript and are identified on the proofs. Unless advised otherwise, please submit all corrections using the CATS online correction form. AQ1. Please provide affiliation for Funda Uysal Tan. AQ2. Please provide a declaration of interest statement. All articles in Informa Healthcare journals should acknowledge any support/funding received by the authors to carry out the study, or any other commercial relationships relevant to the article’s subject matter. If no funding has been received, a statement explicitly declaring no conflict of interest is required.
Neuro-ophthalmology, 00(00), 000–000, 2010 Copyright © 2010 Informa Healthcare USA, Inc. ISSN: 0165-8107 print/ 1744-506X online DOI: 10.3109/01658101003725847
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ORIGINAL ARTICLE
Bilateral Optic Neuritis After Influenza Vaccination AQ1
Funda Uysal Tan, Cengiz Akarsu1, Reyhan Gullu1, and Tulay Kansu2 Kırıkkale University, Faculty of Medicine, Departments of Neurology and Ophthalmology, Turkey 2 Hacettepe University, Faculty of Medicine, Department of Neurology, Turkey
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ABSTRACT Optic neuritis is a rare complication of vaccination. We report a 55-year-old woman who presented with bilateral optic neuritis following influenza vaccination. The patient has typical features of acute optic neuritis with acute visual loss, periocular pain, visual defects, full recovery of vision after 6 months, and the absence of deterioration after withdrawal of corticosteroids. Considering the absence of oligoclonal bands in the cerebrospinal fluid analysis and the nonexistence of lesions resembling multiple sclerosis (MS) in cranial magnetic resonance imaging, the case at present does not appear to be associated with MS. KEYWORDS: Optic neuritis;Vaccination; Influenza
Introduction
pain in the orbits. She was on anticoagulant therapy because of atrial fibrillation. Her past history revealed absence of any allergy, including for egg. Neurological examination was normal, except for ocular signs. Ophthalmologic examination showed best corrected visual acuity of counting fingers at 1 m in the left eye and 3/10 in the right eye. Extraocular motility was intact. Fundoscopy demonstrated mild optic-disc swelling and hyperemia in the right eye and bilateral engorged veins (Figure 1). There was no relative afferent pupil defect. Ishihara plates for color vision were 1/17 on the right and 0/17 on the left. Visual fields on the Humphrey perimeter demonstrated absolute scotoma on the right and superior-nasal defects on the left (Figure 2). Laboratory studies, including complete blood count, erythrocyte sedimentation rate, serum
Optic neuritis is a rare complication of vaccination such as smallpox, hepatitis B, rabies, tetanus toxoid, measles-rubella, and influenza.1–4 The pathophysiology thought to be responsible is immune complex– mediated vascular injury with consequent blood-brain barrier impairment and specific viral antibody synthesis producing inflammation and demyelization of the optic nerve.5–7 We report a patient with bilateral optic neuritis following influenza vaccination.
Case Report A 55-year-old woman was admitted to the neurology outpatient clinic with painful eye movements and bilateral gradual loss of vision for 10 days. Four weeks prior to her visit, she had vaccination with the usual trivalent-inactivated influenza vaccine, which includes two strains of type A and 1 strain of type B, and 3 weeks after that, noted blurry vision and
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Received 17 November 2009; revised 22 February 2010; accepted 23 February 2010 Correspondence: Dr. Funda Uysal Tan, Elçi Sokak 19/18, Y.Ayrancı 06550, Ankara, Turkey. E-mail: fundauysaltan@ yahoo.com
Figure 1 Initial fundoscopy. Mild optic-disc swelling and hyperaemia in the right(R) eye and bilateral engorged veins.
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Figure 2 Humphrey perimeter. Absolute scotoma in the right(R) eye and small spared inferior-temporal area in the left(L) eye.
biochemistry, thyroid function tests, vitamin B12, were all within the normal limits. Rheumatoid factor, C-reactive protein, ANA, Anti-ds DNA, and viral serology were negative. The prothrombin time (PT) was set to the desired range (PT:26.8, INR:2.58). The cerebrospinal fluid analysis was normal with respect to opening pressure, biochemistry, cell, cytology, and gram stain, except for mild protein elevation (63 mg/dl) and the absence of oligoclonal bands was noted. Fundus fluorescent angiography, which was done to rule out any ischemic pathology, depicted the absence of any vascular or macular pathology and presence of bilateral optic disc oedema. Visual-evoked response was normal on the right, but there was no potential on the left. Contrast-enhanced cranial and orbital magnetic resonance imaging (MRI) did not show any lesions resembling multiple sclerosis (MS) and was considered to be normal, except for few millimetric ischemic gliotic lesions in the right-centrum semiovale and bilateral mild enhancement of optic nerves. Thus, the diagnosis was bilateral optic neuritis. The patient was treated with intravenous methylprednisolone (1 g/day) for 5 days followed by slow-tapered oral prednisolone (1 mg/kg/day). No deterioration occurred after withdrawal of corticosteroids. After 6 months, the disk oedema resolved in both eyes and the visual acuity recovered both in the right (9/10) and in the left (8/10) eyes. Mild optic disc pallor was noted on the left (Figure 3). Visual field defects were also mostly improved (Figure 4).
Discussion Influenza virus causes yearly epidemics of respiratory illness of variable morbidity worldwide and one of the most important causes of acute respiratory distress. Therefore, annual immunization programs especially targeting high-risk population are unquestionably beneficial for the control of the disease. However, potential side effects should not be ignored and the patients should be well informed. The patient was vaccinated with the usual trivalent-inactivated influenza vaccine that includes two strains of type A and
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Figure 3 Fundoscopy after treatment. Mild optic-disc pallor was noted in the left(L) eye.
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Figure 4 Humphrey perimeter after treatment showing recovery of visual-field defects.
one strain of type B that induce antibody responses to both viral surface glycoprotein hemagglutinin and neuraminidase. Host defence against influenza virus involves both cellular and humoral pathways, whereas the dentritic cells and cytokines such as interferon and interleukin play a major role in induction of the response.8 The consequence is the host-cell death by cytolytic or apoptotic mechanisms and production of strain-specific antibodies. The mechanism of autoimmunity remains obscure; however, several mechanisms have been suggested, such as epitope spreading, polyclonal activation of T or B cells, and loss of downregulation of dentritic cells.7 One probable cause of autoimmune activation after vaccination is molecular mimicry that is structural similarity between viral and host antigens. Overproduction of cytokines such as interferon or interleukin is also a trigger for the response. The resultant B-cell activation and autoantibody production cause inflammation and demyelinization of the optic nerve with immune complex–mediated vascular injury and bloodbrain barrier impairment.5–7 Optic neuritis is an acute inflammation of the optic nerve. This patient represents typical acute optic neuritis with acute visual loss, periocular pain, visual defects, recovery of visual loss in months, and the absence of deterioration after withdrawal of corticosteroids.6 The disease is mostly unilateral for (70%) most of the patients, but bilateral involvement is also possible.6 It could be an isolated pathology, or it could be associated with MS. The rate of risk of developing MS in acute demyelinating optic neuritis is about 25–30% when the baseline MRI is normal, whereas the risk rate is close to 75% when there are one or more Neuro-ophthalmology
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Bilateral Optic Neuritis After Influenza Vaccination 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
lesions representing MS.6 Thus, MRI of the brain is an important prognostic indicator for the future of MS. In suspected cases, orbital MRI is suggested to eliminate disease processes other than demyelinating optic neuritis that could cause visual loss. In a few case reports, optic neuritis was recorded as a rare complication of vaccinations, for example, those used in preventing smallpox, hepatitis B, polio, tetanus toxoid, measles-rubella, rabies, and influenza.1–4 Arguments were raised about de Novo occurrence rather than a cause–effect relationship. In a case-control study Payne et al. reported no statistically significant association between optic neuritis and anthrax vaccine as well as prior receipt of smallpox, hepatitis B, and influenza vaccinations.9 Similarly, DeStefano et al. stated that vaccination against hepatitis B, influenza, tetanus, measles, or rubella did not increase the risk of MS or optic neuritis.10 However, Toplak and Avcin demonstrated an induction of autoantibodies in healthy people, after influenza vaccination.7 To conclude, postinfluenza vaccination optic neuritis is fortunately very rare, and previous influenza vaccine trials in large population groups mostly found the vaccine as safe considering that the most frequent side effects were only local symptoms related to the injection site.11 Factors such as genetic predisposition, allergic status, gender, hormones, and environment, as well as immune system of the patient itself, are also probable important determinants of autoimmunity. Complete recovery has generally been reported, though incomplete visual recovery may result due to permanent damage to some of the macular fibres.4 Our patient had good recovery of vision following steroid treatment.
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ACKNOWLEDGEMENTS Declaration of interest:
References [1] Hull TP, Bates JH. Optic neuritis after influenza vaccination. Am J Ophthalmol 1997;124:703–704. [2] Ray CL, Dreizin IJ. Bilateral optic neuropathy associated with influenza vaccination. J Neuroophthalmol 1996;16: 182–184. [3] Stevenson VL, Acheson JF, Ball J, Plant GT. Optic neuritis following measles/rubella vaccination in two 13-year-old children. Br J Ophthalmol 1996;80:1110–1111. [4] Gupta V, Bandyopadhyay S, Bapuraj JR, Gupta A. Bilateral optic neuritis complicating rabies vaccination. Retina (Philadelphia, Pa) 2004;24:179–181. [5] Hazin R, Khan F, Bhatti MT. Neuromyelitis optica: current concepts and prospects for future management. Curr Opin Ophthalmol 2009;20:434–439. [6] Shams PN, Plant GT. Optic neuritis: a review. Int MS J 2009;16:82–89. [7] Toplak N, Avcin T. Influenza and autoimmunity. Ann N Y Acad Sci 2009;1173:619–626. [8] Chen J, Deng YM. Influenza virus antigenic variation, host antibody production and new approach to control epidemics. Virol J 2009;6:30. [9] Payne DC, Rose CE Jr, Kerrison J, et al. Anthrax vaccination and risk of optic neuritis in the United States military, 19982003. Arch Neurol 2006;63:871–875. [10] DeStefano F, Verstraeten T, Jackson LA, et al.; Vaccine Safety Datalink Research Group, National Immunization Program, Centers for Disease Control and Prevention. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003;60:504–509. [11] Langley JM, Faughnan ME. Prevention of influenza in the general population. CMAJ 2004;171: 1213–1222.
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