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J Vet Clin 2023; 40(5): 336-340

https://doi.org/10.17555/jvc.2023.40.5.336

Published online October 31, 2023

Facial Paralysis and Myositis Following the H3N2 Influenza Vaccine in a Dog

Ju-Hyun An1 , Ye-In Oh2 , So-Hee Kim3 , Su-Min Park3 , Jeong-Hwa Lee3 , Ga-Hyun Lim3 , Kyung-Won Seo3 , Hwa-Young Youn3,*

1Department of Veterinary Emergency and Critical Care Medicine and Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Korea
2Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
3Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea

Correspondence to:*hyyoun@snu.ac.kr

Received: July 3, 2023; Revised: September 27, 2023; Accepted: October 4, 2023

Copyright © The Korean Society of Veterinary Clinics.

A dog (2-year old, female, Shih-Tzu) presented with hyperthermia and right-sided facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after H3N2 influenza vaccination [A/ Canine/Korea/01/07(H3N2) strain; Caniflu-Max, Bionote, Hwaseong, Gyeonggi-do, ROK]. To determine the cause of the fever and neurological symptoms, physical examination, ophthalmic examination, thoracic and abdominal radiography, abdominal ultrasonography, complete blood counts, serum chemistry values, and electrolyte levels were determined. In addition, Cerebrospinal fluid analysis, antinuclear antibody test, fever of unknown origin polymerase chain reaction (PCR) panel, tick-borne pathogen PCR panel were performed. As a result, hyperthermia, leukocytosis, and elevated C-reactive protein were confirmed. In addition, neurological examination revealed decreased right eyelid reflexes, corneal reflexes, threat response, and facial sensation, it was possible to suspect problems with the trigeminal and facial nerves of the cranial nerve. Magnetic resonance imaging revealed a lesion suggestive of myositis in the right muscular lesion at atlanto-occipital junction level on site of vaccine injection. Therefore, right-sided facial paralysis was tentatively determined to be a secondary cause of nerve damage caused by myositis. The patient was treated with immunosuppressants such as prednisolone and mycophenolate mofetil. After 3 months of immunosuppressant therapy, the patient’s symptoms improved.

Keywords: facial paralysis, influenza vaccine, myositis, magnetic resonance imaging, neurological complications.

Influenza virus infection can cause an acute febrile respiratory illness that necessitates treatment in dogs. H3N2 is the subtype of influenza virus that has been identified in the Republic of Korea (ROK) since 2007 (16). Therefore, annual H3N2 influenza vaccination is recommended for healthy young dogs in the ROK (15). Commonly occurring side effects of influenza vaccines in humans are redness, pain, and swelling at the injection site, which reportedly occurs in 20% of all vaccine recipients (14,28,29). Several neurological complications of influenza vaccination have been reported, such as Guillain–Barre syndrome (10) and chronic inflammatory demyelinating polyneuropathy (5), although they are uncommon and their association with the vaccine has not been adequately established. Facial paralysis is a neurological adverse effect of concern (24). However, there are limited case reports of neurological complications following influenza vaccination in dogs. Here, we describe the case of a dog with right-sided facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after influenza vaccination.

A 2-year-old, female, Shih-Tzu presented with hyperthermia, weakness, and right eye blinking disorder. One month before admission, the patient received an influenza vaccine containing the H3N2 influenza virus [A/Canine/Korea/ 01/07(H3N2) strain; Caniflu-Max, Bionote, Hwaseong, ROK] by intramuscular injection into the back of the neck at a local animal hospital. Five days after vaccination, the patient was lethargic and had a fever. Nine days following vaccination, the patient developed additional symptoms, including right facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth, which were duly verified.

To determine the cause of the fever and neurological symptoms, physical examination, ophthalmic examination, thoracic and abdominal radiography, abdominal ultrasonography, complete blood counts, serum chemistry values, and electrolyte levels were determined.

On physical examination, the patient’s vital signs were as follows: heart rate, 120/minute; systolic blood pressure, 105 mmHg; respiratory rate, 24/minute; and body temperature, 40°C. A neurological examination was conducted, including assessment of mental status, posture, gait, cranial nerves, postural reactions, spinal reflexes, sensitivity to spinal palpation, and pain perception. Consequently, the examination disclosed reduced right eyelid reflex, corneal reflex, menace response, and facial sensation, with no abnormalities were observed in the remainder of the assessment. Blood test results showed a white blood cell count of 30.12 × 103/μL (reference range: 5.05-16.76 × 103/μL), hemoglobin level of 10.0 g/dL (reference range, 13.1-20.5 g/dL), hematocrit concentration of 27.7% (reference range: 37.3-61.7%) and C-reactive protein level of 158.9 mg/L (reference range: 0-20 mg/L). Other blood tests showed no remarkable findings. Additional tests were also conducted to closely check the patient’s condition. Antinuclear antibody test results were negative, and a fever of unknown origin polymerase chain reaction panel (IDEXX Laboratories, Inc. Seoul, ROK) showed negative results for DNA amplification of Babesia spp., Anaplasma spp., Ehrlichia spp., Rickettsia spp., Hepatozoon spp., Histoplasma capsulatum, Brucella canis, Bartonella spp., Cryptococcus spp., Toxoplasma gondii, Blastomyces dermatitidis, Coccidioides spp., Neospora caninum, Leishmania spp., Leptospira spp., and Trypanosoma cruzi. Additionally, a tickborne pathogens panel (Pobanilab Laboratories, Guri, ROK) preformed at a local hospital before the patient was brought to us showed negative results for DNA amplification of Anaplasma spp., Ehrlichia spp., Babesia spp., Lyme borreliosis, Bartonella spp., Hemotropic mycoplasma, Rickettia spp., Leptospira spp., Hepatozytozoon spp., and Theilera spp. This patient additionally underwent magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) tests at a local hospital. Fat-saturated T1-weighted MRI revealed hyperintense signal changes in the right muscular lesion at atlanto-occipital junction level, which was suggestive of myositis (Fig. 1). The right retropharyngeal lymph node was enlarged. In addition, slight meningeal enhancement at the posterior medulla oblongata and at the level of the atlas was confirmed. CSF was collected from the cerebellomedullary cistern though puncture; however, no significant abnormalities were observed on cytology. EMG and muscle biopsy could not be carried out as the patient owner did not give consent. Considering the overall neurological examination, there were abnormalities in the sensory and motor nerves of the right side of the face, and taking this together, it was possible to suspect problems with the trigeminal and facial nerves of the cranial nerve. Since EMG and biopsy were not performed, there are limitations in carefully diagnosing the nerve condition. However, when conducting an MRI examination, there were no abnormalities in the nucleus of the cranial nerve, and the area of the muscle that could cause problems with the projection of the cranial nerve suspected inflammatory findings were confirmed. Therefore, right-sided facial paralysis was tentatively determined to be a secondary cause of nerve damage caused by myositis.

Figure 1.Hyperintense signal changes on the fat saturated T1 weighted image with GAD in the right muscular lesion at atlanto-occipital junction level in MRI scan. (A) View of transverse, fat-saturated of T1-weighted, post contrast. (B) View of dorsal, fat saturated of T1 weighted, post-contrast. GAD, gadolinium.

Because the patient had shown temporary improvement with prednisolone (PDS, 0.5 mg/kg, orally, twice a day) therapy, which had been prescribed at a local hospital and immune-mediated myositis was considered preferentially, the steroid dose was increased (1 mg/kg, orally, twice a day). Additionally, because systemic infection was tentatively ruled out, the antibiotics (amoxicillin clavulanate, 22 mg/kg PO bid; marbofloxacin, 2 mg/kg PO sid; metronidazole, 15 mg/kg PO bid) prescribed at the first visit were discontinued. 10 days after admission, the patient’s body temperature was maintained at 39.5°C, and the appetite and vitality were good. The C-reactive protein level was within the normal range. However, the inability to close the right eye persisted. Therefore, a secondary immunosuppressant was added (mycophenolate mofetil [MMF], 12 mg/kg, orally, twice a day). 24 days after admission, the disclosed reduced right eyelid reflex, corneal reflex, menace response, and facial sensation had improved. Therefore, PDS and MMF were gradually tapered over 3 months. Three months after treatment cessation, the patient is doing well and has no initial neurological symptoms.

Post-vaccination complications generally occur due to procedure-related local trauma, irritant vaccine constituents, inappropriate injection techniques, or injection of intramuscular medication in the artery and veins (18), which can result in bleeding, persistent pain, abscess and scar formation, surrounding tissue necrosis, muscle fibrosis, and development of malignancy at the injection site (6). In addition to these, there have also been documented instances of uncommon and severe adverse responses, such as thrombosis with thrombocytopenia syndrome (8), Guillain-Barré syndrome (12), vasculitis (7), autoimmune hepatitis (21), inflammatory myopathies, and myocarditis (30). These are now believed to result from immune-mediated mechanisms.

Our patient developed right facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after H3N2 influenza vaccination. Unfortunately, the owner does not agree, an EMG test was not conducted. In addition, while IDEXX FUO PCR, ANA test, and Pobanilab tick-borne pathogen panel were administered, no tissue examination, such as biopsy or culture testing, was undertaken. Consequently, the possibility of infections and immune-related diseases affecting the lesion site could not be completely excluded. However, MRI revealed myositis at the injection site, which could have caused facial nerve irritation.

In this case, although this idiopathic facial paralysis cannot be completely ruled out, considering that myositis was confirmed at the injection site and facial paralysis was confirmed after injection, facial paralysis accompanied by myositis after vaccine injection is most suspected. In addition, after receiving a vaccine at a local hospital, she visited our hospital with symptoms of facial paralysis that persisted for a long time, and needed medication.

There are a few reports of vaccine-induced neurological disorders and myositis in humans. Chou et al. (4) reported two cases of right facial neuropathy after influenza vaccination, diagnosed based on facial nerve conduction studies and blink reflex testing. Cases of acute disseminated encephalomyelitis and transverse myelitis with acute motor axonal neuropathy after influenza vaccination have been reported (19). Although these reports discuss several possible causes of myositis (22) such as viral infection (12) and autoimmunity (10), the relationship between influenza vaccination and neurological complications such as facial paralysis and neuritis has not been clearly established (23). Additionally, a 60-year-old man developed polyarthropathy, orbital myositis, and posterior scleritis 10 days after receiving the 1993 Fluvirin vaccine. Because there was ocular involvement, he was prescribed oral prednisolone and acetazolamide, with dramatic improvement over four months (27). Belliveau reported the case of a patient with orbital inflammation and posterior scleritis hours after receiving Arepanrix (GlaxoSmithKline, Quebec, Canada), an H1N1 influenza vaccine. The patient was treated with oral and topical steroids and showed complete symptom resolution within 2 weeks (2). Although the mechanism of vaccine-related autoimmune disease is unclear, several studies report a correlation between vaccine administration and inflammatory myopathy, a rare phenomenon presumed to be due to an autoimmune reaction (3,20,25,27).

However, it is unclear whether our patient’s symptoms were due to the adverse effects of the vaccine itself or to reactions to antigens or adjuvants. Adjuvants such as adsorbent aluminum hydroxide gel are often used with vaccines (9,11). They enhance the antigen-specific immune response, ideally without triggering an immune reaction, and are commonly used to boost the immune response to vaccination (17). In previous reports, side effects of adjuvants have been reported (1,13). There have been cases of myositis, myocarditis, and rhabdomyolysis after administration of the seasonal influenza vaccine, possibly due to the immunogenicity of the vaccine adjuvant. This has been termed “adjuvant-induced autoimmune/inflammatory syndrome“ (1).

Considering everything, it was determined that this patient’s facial paralysis was most likely secondary to myositis caused by vaccination, and PDS and MMF treatments were performed to treat vaccine-induced myositis. In veterinary medicine, there is still insufficient evidence for treatment guidelines for vaccine-induced myositis. In human medicine, there have been cases of vaccine-induced myositis that were treated with glucocorticoids and immunosuppressants (26). All these cases were treated with immunosuppression, including glucocorticoids, intravenous immune globulin, cyclophosphamide, methotrexate, hydroxychloroquine, MMF, and tocilizumab. However, it has not yet been studied which of these immunosuppressants has better results, and further research is needed.

We report a rare case of facial paralysis and myositis after influenza vaccination in a dog. Vaccination may cause neurological symptoms in dogs, and these symptoms can be effectively managed with immunosuppressive drugs such as PDS and MMF.

Written informed consent for publication of the clinical detail was obtained from the dog’s owner.

It was partially supported by the Research Institute for Veterinary Science, Seoul National University. The design of the study including collection, analysis, and interpretation of data, and in writing the manuscript were not influenced by the funders.

JHA, YIO, SHK, SMP, THK, KYS and HYY analyzed and interpreted patient data. JHA was a main contributor in writing manuscript. JHA, YIO, SHK, SMP, THK, KYS and HYY performed imaging evaluation and contributed to imaging descriptions and discussions in this manuscript. All authors read and approved the final manuscript.

  1. Ameratunga R, Gillis D, Gold M, Linneberg A, Elwood JM. Evidence refuting the existence of autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). J Allergy Clin Immunol Pract 2017; 5: 1551-1555.e1.
    Pubmed CrossRef
  2. Belliveau M. Influenza A virus vaccine-H1N1. Orbital inflammatory syndrome induced by AS03A adjuvant: case report. React Wkly 2012; 1392: 29.
    CrossRef
  3. Cavalcanti JFB, Silva MBA, Alves de Siqueira Carvalho A. Vaccination as a possible trigger for immune-mediated necrotising myopathy. BMJ Case Rep 2021; 14: e242095.
    Pubmed KoreaMed CrossRef
  4. Chou CH, Liou WP, Hu KI, Loh CH, Chou CC, Chen YH. Bell's palsy associated with influenza vaccination: two case reports. Vaccine 2007; 25: 2839-2841.
    Pubmed CrossRef
  5. Créange A, Temam G, Lefaucheur JP. Lumbosacral acute demyelinating polyneuropathy following hepatitis B vaccination. Autoimmunity 1999; 30: 143-146.
    Pubmed CrossRef
  6. Dehn RW, Asprey DP. Essential clinical procedures. 3rd ed. Philadelphia: Elsevier Saunders. 2013.
    CrossRef
  7. Godoy IRB, Rodrigues TC, Skaf A. Myositis ossificans following COVID-19 vaccination. QJM 2021; 114: 659-660.
    Pubmed KoreaMed CrossRef
  8. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021; 384: 2092-2101.
    Pubmed KoreaMed CrossRef
  9. Gupta RK. Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 1998; 32: 155-172.
    Pubmed CrossRef
  10. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf 2009; 32: 309-323.
    Pubmed CrossRef
  11. Hem SL, White JL. Structure and properties of aluminum-containing adjuvants. Pharm Biotechnol 1995; 6: 249-276.
    Pubmed CrossRef
  12. Israeli E, Agmon-Levin N, Blank M, Chapman J, Shoenfeld Y. Guillain-Barré syndrome-a classical autoimmune disease triggered by infection or vaccination. Clin Rev Allergy Immunol 2012; 42: 121-130.
    Pubmed CrossRef
  13. Jiao XD, Cheng S, Hu YH, Sun L. Comparative study of the effects of aluminum adjuvants and Freund's incomplete adjuvant on the immune response to an Edwardsiella tarda major antigen. Vaccine 2010; 28: 1832-1837.
    Pubmed CrossRef
  14. Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev 2018; 6: CD002733.
    Pubmed KoreaMed CrossRef
  15. Lee C, Jung K, Oh J, Oh T, Han S, Hwang J, et al. Protective efficacy and immunogenicity of an inactivated avian-origin H3N2 canine influenza vaccine in dogs challenged with the virulent virus. Vet Microbiol 2010; 143: 184-188.
    Pubmed CrossRef
  16. Lee YN, Lee DH, Lee HJ, Park JK, Yuk SS, Sung HJ, et al. Evidence of H3N2 canine influenza virus infection before 2007. Vet Rec 2012; 171: 477.
    Pubmed CrossRef
  17. McNeil MM, DeStefano F. Vaccine-associated hypersensitivity. J Allergy Clin Immunol 2018; 141: 463-472.
    Pubmed KoreaMed CrossRef
  18. Moore GE, HogenEsch H. Adverse vaccinal events in dogs and cats. Vet Clin North Am Small Anim Pract 2010; 40: 393-407.
    Pubmed CrossRef
  19. Nakamura N, Nokura K, Zettsu T, Koga H, Tachi M, Terada M, et al. Neurologic complications associated with influenza vaccination: two adult cases. Intern Med 2003; 42: 191-194.
    Pubmed CrossRef
  20. Orbach H, Tanay A. Vaccines as a trigger for myopathies. Lupus 2009; 18: 1213-1216.
    Pubmed CrossRef
  21. Rela M, Jothimani D, Vij M, Rajakumar A, Rammohan A. Auto-immune hepatitis following COVID vaccination. J Autoimmun 2021; 123: 102688.
    Pubmed CrossRef
  22. Sakthivadivel V, Naveenraj P, Kachhwaha A, Kumar D, Anne PB, Elhence P, et al. Concurrent acute myositis and Guillain-Barre syndrome in Cytomegalovirus infection - a rare case report. BMC In. fect Dis 2020; 20: 768.
    CrossRef
  23. Souayah N, Nasar A, Suri MF, Qureshi AI. Guillain-Barre syndrome after vaccination in United States a report from the CDC/FDA Vaccine Adverse Event Reporting System. Vaccine 2007; 25: 5253-5255.
    Pubmed CrossRef
  24. Stowe J, Andrews N, Wise L, Miller E. Bell's palsy and parenteral inactivated influenza vaccine. Hum Vaccin 2006; 2: 110-112.
    Pubmed CrossRef
  25. Stübgen JP. A review on the association between inflammatory myopathies and vaccination. Autoimmun Rev 2014; 13: 31-39.
    Pubmed CrossRef
  26. Syrmou V, Liaskos C, Ntavari N, Mitsimponas K, Simopoulou T, Alexiou I, et al. COVID-19 vaccine-associated myositis: a comprehensive review of the literature driven by a case report. Immunol Res 2023; 71: 537-546.
    Pubmed KoreaMed CrossRef
  27. Thurairajan G, Hope-Ross MW, Situnayake RD, Murray PI. Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine. Br J Rheumatol 1997; 36: 120-123.
    Pubmed CrossRef
  28. Tregoning JS, Russell RF, Kinnear E. Adjuvanted influenza vaccines. Hum Vaccin Immunother 2018; 14: 550-564.
    Pubmed KoreaMed CrossRef
  29. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine 2009; 27: 2114-2120.
    Pubmed CrossRef
  30. Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, et al. Myocarditis after COVID-19 vaccination in a large health care organization. N Engl J Med 2021; 385: 2132-2139.
    Pubmed KoreaMed CrossRef

Article

Case Report

J Vet Clin 2023; 40(5): 336-340

Published online October 31, 2023 https://doi.org/10.17555/jvc.2023.40.5.336

Copyright © The Korean Society of Veterinary Clinics.

Facial Paralysis and Myositis Following the H3N2 Influenza Vaccine in a Dog

Ju-Hyun An1 , Ye-In Oh2 , So-Hee Kim3 , Su-Min Park3 , Jeong-Hwa Lee3 , Ga-Hyun Lim3 , Kyung-Won Seo3 , Hwa-Young Youn3,*

1Department of Veterinary Emergency and Critical Care Medicine and Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Korea
2Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
3Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea

Correspondence to:*hyyoun@snu.ac.kr

Received: July 3, 2023; Revised: September 27, 2023; Accepted: October 4, 2023

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A dog (2-year old, female, Shih-Tzu) presented with hyperthermia and right-sided facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after H3N2 influenza vaccination [A/ Canine/Korea/01/07(H3N2) strain; Caniflu-Max, Bionote, Hwaseong, Gyeonggi-do, ROK]. To determine the cause of the fever and neurological symptoms, physical examination, ophthalmic examination, thoracic and abdominal radiography, abdominal ultrasonography, complete blood counts, serum chemistry values, and electrolyte levels were determined. In addition, Cerebrospinal fluid analysis, antinuclear antibody test, fever of unknown origin polymerase chain reaction (PCR) panel, tick-borne pathogen PCR panel were performed. As a result, hyperthermia, leukocytosis, and elevated C-reactive protein were confirmed. In addition, neurological examination revealed decreased right eyelid reflexes, corneal reflexes, threat response, and facial sensation, it was possible to suspect problems with the trigeminal and facial nerves of the cranial nerve. Magnetic resonance imaging revealed a lesion suggestive of myositis in the right muscular lesion at atlanto-occipital junction level on site of vaccine injection. Therefore, right-sided facial paralysis was tentatively determined to be a secondary cause of nerve damage caused by myositis. The patient was treated with immunosuppressants such as prednisolone and mycophenolate mofetil. After 3 months of immunosuppressant therapy, the patient’s symptoms improved.

Keywords: facial paralysis, influenza vaccine, myositis, magnetic resonance imaging, neurological complications.

Introduction

Influenza virus infection can cause an acute febrile respiratory illness that necessitates treatment in dogs. H3N2 is the subtype of influenza virus that has been identified in the Republic of Korea (ROK) since 2007 (16). Therefore, annual H3N2 influenza vaccination is recommended for healthy young dogs in the ROK (15). Commonly occurring side effects of influenza vaccines in humans are redness, pain, and swelling at the injection site, which reportedly occurs in 20% of all vaccine recipients (14,28,29). Several neurological complications of influenza vaccination have been reported, such as Guillain–Barre syndrome (10) and chronic inflammatory demyelinating polyneuropathy (5), although they are uncommon and their association with the vaccine has not been adequately established. Facial paralysis is a neurological adverse effect of concern (24). However, there are limited case reports of neurological complications following influenza vaccination in dogs. Here, we describe the case of a dog with right-sided facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after influenza vaccination.

Case Report

A 2-year-old, female, Shih-Tzu presented with hyperthermia, weakness, and right eye blinking disorder. One month before admission, the patient received an influenza vaccine containing the H3N2 influenza virus [A/Canine/Korea/ 01/07(H3N2) strain; Caniflu-Max, Bionote, Hwaseong, ROK] by intramuscular injection into the back of the neck at a local animal hospital. Five days after vaccination, the patient was lethargic and had a fever. Nine days following vaccination, the patient developed additional symptoms, including right facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth, which were duly verified.

To determine the cause of the fever and neurological symptoms, physical examination, ophthalmic examination, thoracic and abdominal radiography, abdominal ultrasonography, complete blood counts, serum chemistry values, and electrolyte levels were determined.

On physical examination, the patient’s vital signs were as follows: heart rate, 120/minute; systolic blood pressure, 105 mmHg; respiratory rate, 24/minute; and body temperature, 40°C. A neurological examination was conducted, including assessment of mental status, posture, gait, cranial nerves, postural reactions, spinal reflexes, sensitivity to spinal palpation, and pain perception. Consequently, the examination disclosed reduced right eyelid reflex, corneal reflex, menace response, and facial sensation, with no abnormalities were observed in the remainder of the assessment. Blood test results showed a white blood cell count of 30.12 × 103/μL (reference range: 5.05-16.76 × 103/μL), hemoglobin level of 10.0 g/dL (reference range, 13.1-20.5 g/dL), hematocrit concentration of 27.7% (reference range: 37.3-61.7%) and C-reactive protein level of 158.9 mg/L (reference range: 0-20 mg/L). Other blood tests showed no remarkable findings. Additional tests were also conducted to closely check the patient’s condition. Antinuclear antibody test results were negative, and a fever of unknown origin polymerase chain reaction panel (IDEXX Laboratories, Inc. Seoul, ROK) showed negative results for DNA amplification of Babesia spp., Anaplasma spp., Ehrlichia spp., Rickettsia spp., Hepatozoon spp., Histoplasma capsulatum, Brucella canis, Bartonella spp., Cryptococcus spp., Toxoplasma gondii, Blastomyces dermatitidis, Coccidioides spp., Neospora caninum, Leishmania spp., Leptospira spp., and Trypanosoma cruzi. Additionally, a tickborne pathogens panel (Pobanilab Laboratories, Guri, ROK) preformed at a local hospital before the patient was brought to us showed negative results for DNA amplification of Anaplasma spp., Ehrlichia spp., Babesia spp., Lyme borreliosis, Bartonella spp., Hemotropic mycoplasma, Rickettia spp., Leptospira spp., Hepatozytozoon spp., and Theilera spp. This patient additionally underwent magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) tests at a local hospital. Fat-saturated T1-weighted MRI revealed hyperintense signal changes in the right muscular lesion at atlanto-occipital junction level, which was suggestive of myositis (Fig. 1). The right retropharyngeal lymph node was enlarged. In addition, slight meningeal enhancement at the posterior medulla oblongata and at the level of the atlas was confirmed. CSF was collected from the cerebellomedullary cistern though puncture; however, no significant abnormalities were observed on cytology. EMG and muscle biopsy could not be carried out as the patient owner did not give consent. Considering the overall neurological examination, there were abnormalities in the sensory and motor nerves of the right side of the face, and taking this together, it was possible to suspect problems with the trigeminal and facial nerves of the cranial nerve. Since EMG and biopsy were not performed, there are limitations in carefully diagnosing the nerve condition. However, when conducting an MRI examination, there were no abnormalities in the nucleus of the cranial nerve, and the area of the muscle that could cause problems with the projection of the cranial nerve suspected inflammatory findings were confirmed. Therefore, right-sided facial paralysis was tentatively determined to be a secondary cause of nerve damage caused by myositis.

Figure 1. Hyperintense signal changes on the fat saturated T1 weighted image with GAD in the right muscular lesion at atlanto-occipital junction level in MRI scan. (A) View of transverse, fat-saturated of T1-weighted, post contrast. (B) View of dorsal, fat saturated of T1 weighted, post-contrast. GAD, gadolinium.

Because the patient had shown temporary improvement with prednisolone (PDS, 0.5 mg/kg, orally, twice a day) therapy, which had been prescribed at a local hospital and immune-mediated myositis was considered preferentially, the steroid dose was increased (1 mg/kg, orally, twice a day). Additionally, because systemic infection was tentatively ruled out, the antibiotics (amoxicillin clavulanate, 22 mg/kg PO bid; marbofloxacin, 2 mg/kg PO sid; metronidazole, 15 mg/kg PO bid) prescribed at the first visit were discontinued. 10 days after admission, the patient’s body temperature was maintained at 39.5°C, and the appetite and vitality were good. The C-reactive protein level was within the normal range. However, the inability to close the right eye persisted. Therefore, a secondary immunosuppressant was added (mycophenolate mofetil [MMF], 12 mg/kg, orally, twice a day). 24 days after admission, the disclosed reduced right eyelid reflex, corneal reflex, menace response, and facial sensation had improved. Therefore, PDS and MMF were gradually tapered over 3 months. Three months after treatment cessation, the patient is doing well and has no initial neurological symptoms.

Discussion

Post-vaccination complications generally occur due to procedure-related local trauma, irritant vaccine constituents, inappropriate injection techniques, or injection of intramuscular medication in the artery and veins (18), which can result in bleeding, persistent pain, abscess and scar formation, surrounding tissue necrosis, muscle fibrosis, and development of malignancy at the injection site (6). In addition to these, there have also been documented instances of uncommon and severe adverse responses, such as thrombosis with thrombocytopenia syndrome (8), Guillain-Barré syndrome (12), vasculitis (7), autoimmune hepatitis (21), inflammatory myopathies, and myocarditis (30). These are now believed to result from immune-mediated mechanisms.

Our patient developed right facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after H3N2 influenza vaccination. Unfortunately, the owner does not agree, an EMG test was not conducted. In addition, while IDEXX FUO PCR, ANA test, and Pobanilab tick-borne pathogen panel were administered, no tissue examination, such as biopsy or culture testing, was undertaken. Consequently, the possibility of infections and immune-related diseases affecting the lesion site could not be completely excluded. However, MRI revealed myositis at the injection site, which could have caused facial nerve irritation.

In this case, although this idiopathic facial paralysis cannot be completely ruled out, considering that myositis was confirmed at the injection site and facial paralysis was confirmed after injection, facial paralysis accompanied by myositis after vaccine injection is most suspected. In addition, after receiving a vaccine at a local hospital, she visited our hospital with symptoms of facial paralysis that persisted for a long time, and needed medication.

There are a few reports of vaccine-induced neurological disorders and myositis in humans. Chou et al. (4) reported two cases of right facial neuropathy after influenza vaccination, diagnosed based on facial nerve conduction studies and blink reflex testing. Cases of acute disseminated encephalomyelitis and transverse myelitis with acute motor axonal neuropathy after influenza vaccination have been reported (19). Although these reports discuss several possible causes of myositis (22) such as viral infection (12) and autoimmunity (10), the relationship between influenza vaccination and neurological complications such as facial paralysis and neuritis has not been clearly established (23). Additionally, a 60-year-old man developed polyarthropathy, orbital myositis, and posterior scleritis 10 days after receiving the 1993 Fluvirin vaccine. Because there was ocular involvement, he was prescribed oral prednisolone and acetazolamide, with dramatic improvement over four months (27). Belliveau reported the case of a patient with orbital inflammation and posterior scleritis hours after receiving Arepanrix (GlaxoSmithKline, Quebec, Canada), an H1N1 influenza vaccine. The patient was treated with oral and topical steroids and showed complete symptom resolution within 2 weeks (2). Although the mechanism of vaccine-related autoimmune disease is unclear, several studies report a correlation between vaccine administration and inflammatory myopathy, a rare phenomenon presumed to be due to an autoimmune reaction (3,20,25,27).

However, it is unclear whether our patient’s symptoms were due to the adverse effects of the vaccine itself or to reactions to antigens or adjuvants. Adjuvants such as adsorbent aluminum hydroxide gel are often used with vaccines (9,11). They enhance the antigen-specific immune response, ideally without triggering an immune reaction, and are commonly used to boost the immune response to vaccination (17). In previous reports, side effects of adjuvants have been reported (1,13). There have been cases of myositis, myocarditis, and rhabdomyolysis after administration of the seasonal influenza vaccine, possibly due to the immunogenicity of the vaccine adjuvant. This has been termed “adjuvant-induced autoimmune/inflammatory syndrome“ (1).

Considering everything, it was determined that this patient’s facial paralysis was most likely secondary to myositis caused by vaccination, and PDS and MMF treatments were performed to treat vaccine-induced myositis. In veterinary medicine, there is still insufficient evidence for treatment guidelines for vaccine-induced myositis. In human medicine, there have been cases of vaccine-induced myositis that were treated with glucocorticoids and immunosuppressants (26). All these cases were treated with immunosuppression, including glucocorticoids, intravenous immune globulin, cyclophosphamide, methotrexate, hydroxychloroquine, MMF, and tocilizumab. However, it has not yet been studied which of these immunosuppressants has better results, and further research is needed.

Conclusions

We report a rare case of facial paralysis and myositis after influenza vaccination in a dog. Vaccination may cause neurological symptoms in dogs, and these symptoms can be effectively managed with immunosuppressive drugs such as PDS and MMF.

Acknowledgements

Written informed consent for publication of the clinical detail was obtained from the dog’s owner.

Source of Funding

It was partially supported by the Research Institute for Veterinary Science, Seoul National University. The design of the study including collection, analysis, and interpretation of data, and in writing the manuscript were not influenced by the funders.

Authors’ Contributions

JHA, YIO, SHK, SMP, THK, KYS and HYY analyzed and interpreted patient data. JHA was a main contributor in writing manuscript. JHA, YIO, SHK, SMP, THK, KYS and HYY performed imaging evaluation and contributed to imaging descriptions and discussions in this manuscript. All authors read and approved the final manuscript.

Conflicts of Interest

The authors have no conflicting interests.

Ethics Approval

Not applicable.

Fig 1.

Figure 1.Hyperintense signal changes on the fat saturated T1 weighted image with GAD in the right muscular lesion at atlanto-occipital junction level in MRI scan. (A) View of transverse, fat-saturated of T1-weighted, post contrast. (B) View of dorsal, fat saturated of T1 weighted, post-contrast. GAD, gadolinium.
Journal of Veterinary Clinics 2023; 40: 336-340https://doi.org/10.17555/jvc.2023.40.5.336

References

  1. Ameratunga R, Gillis D, Gold M, Linneberg A, Elwood JM. Evidence refuting the existence of autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). J Allergy Clin Immunol Pract 2017; 5: 1551-1555.e1.
    Pubmed CrossRef
  2. Belliveau M. Influenza A virus vaccine-H1N1. Orbital inflammatory syndrome induced by AS03A adjuvant: case report. React Wkly 2012; 1392: 29.
    CrossRef
  3. Cavalcanti JFB, Silva MBA, Alves de Siqueira Carvalho A. Vaccination as a possible trigger for immune-mediated necrotising myopathy. BMJ Case Rep 2021; 14: e242095.
    Pubmed KoreaMed CrossRef
  4. Chou CH, Liou WP, Hu KI, Loh CH, Chou CC, Chen YH. Bell's palsy associated with influenza vaccination: two case reports. Vaccine 2007; 25: 2839-2841.
    Pubmed CrossRef
  5. Créange A, Temam G, Lefaucheur JP. Lumbosacral acute demyelinating polyneuropathy following hepatitis B vaccination. Autoimmunity 1999; 30: 143-146.
    Pubmed CrossRef
  6. Dehn RW, Asprey DP. Essential clinical procedures. 3rd ed. Philadelphia: Elsevier Saunders. 2013.
    CrossRef
  7. Godoy IRB, Rodrigues TC, Skaf A. Myositis ossificans following COVID-19 vaccination. QJM 2021; 114: 659-660.
    Pubmed KoreaMed CrossRef
  8. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021; 384: 2092-2101.
    Pubmed KoreaMed CrossRef
  9. Gupta RK. Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 1998; 32: 155-172.
    Pubmed CrossRef
  10. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf 2009; 32: 309-323.
    Pubmed CrossRef
  11. Hem SL, White JL. Structure and properties of aluminum-containing adjuvants. Pharm Biotechnol 1995; 6: 249-276.
    Pubmed CrossRef
  12. Israeli E, Agmon-Levin N, Blank M, Chapman J, Shoenfeld Y. Guillain-Barré syndrome-a classical autoimmune disease triggered by infection or vaccination. Clin Rev Allergy Immunol 2012; 42: 121-130.
    Pubmed CrossRef
  13. Jiao XD, Cheng S, Hu YH, Sun L. Comparative study of the effects of aluminum adjuvants and Freund's incomplete adjuvant on the immune response to an Edwardsiella tarda major antigen. Vaccine 2010; 28: 1832-1837.
    Pubmed CrossRef
  14. Kopsaftis Z, Wood-Baker R, Poole P. Influenza vaccine for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev 2018; 6: CD002733.
    Pubmed KoreaMed CrossRef
  15. Lee C, Jung K, Oh J, Oh T, Han S, Hwang J, et al. Protective efficacy and immunogenicity of an inactivated avian-origin H3N2 canine influenza vaccine in dogs challenged with the virulent virus. Vet Microbiol 2010; 143: 184-188.
    Pubmed CrossRef
  16. Lee YN, Lee DH, Lee HJ, Park JK, Yuk SS, Sung HJ, et al. Evidence of H3N2 canine influenza virus infection before 2007. Vet Rec 2012; 171: 477.
    Pubmed CrossRef
  17. McNeil MM, DeStefano F. Vaccine-associated hypersensitivity. J Allergy Clin Immunol 2018; 141: 463-472.
    Pubmed KoreaMed CrossRef
  18. Moore GE, HogenEsch H. Adverse vaccinal events in dogs and cats. Vet Clin North Am Small Anim Pract 2010; 40: 393-407.
    Pubmed CrossRef
  19. Nakamura N, Nokura K, Zettsu T, Koga H, Tachi M, Terada M, et al. Neurologic complications associated with influenza vaccination: two adult cases. Intern Med 2003; 42: 191-194.
    Pubmed CrossRef
  20. Orbach H, Tanay A. Vaccines as a trigger for myopathies. Lupus 2009; 18: 1213-1216.
    Pubmed CrossRef
  21. Rela M, Jothimani D, Vij M, Rajakumar A, Rammohan A. Auto-immune hepatitis following COVID vaccination. J Autoimmun 2021; 123: 102688.
    Pubmed CrossRef
  22. Sakthivadivel V, Naveenraj P, Kachhwaha A, Kumar D, Anne PB, Elhence P, et al. Concurrent acute myositis and Guillain-Barre syndrome in Cytomegalovirus infection - a rare case report. BMC In. fect Dis 2020; 20: 768.
    CrossRef
  23. Souayah N, Nasar A, Suri MF, Qureshi AI. Guillain-Barre syndrome after vaccination in United States a report from the CDC/FDA Vaccine Adverse Event Reporting System. Vaccine 2007; 25: 5253-5255.
    Pubmed CrossRef
  24. Stowe J, Andrews N, Wise L, Miller E. Bell's palsy and parenteral inactivated influenza vaccine. Hum Vaccin 2006; 2: 110-112.
    Pubmed CrossRef
  25. Stübgen JP. A review on the association between inflammatory myopathies and vaccination. Autoimmun Rev 2014; 13: 31-39.
    Pubmed CrossRef
  26. Syrmou V, Liaskos C, Ntavari N, Mitsimponas K, Simopoulou T, Alexiou I, et al. COVID-19 vaccine-associated myositis: a comprehensive review of the literature driven by a case report. Immunol Res 2023; 71: 537-546.
    Pubmed KoreaMed CrossRef
  27. Thurairajan G, Hope-Ross MW, Situnayake RD, Murray PI. Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine. Br J Rheumatol 1997; 36: 120-123.
    Pubmed CrossRef
  28. Tregoning JS, Russell RF, Kinnear E. Adjuvanted influenza vaccines. Hum Vaccin Immunother 2018; 14: 550-564.
    Pubmed KoreaMed CrossRef
  29. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine 2009; 27: 2114-2120.
    Pubmed CrossRef
  30. Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, et al. Myocarditis after COVID-19 vaccination in a large health care organization. N Engl J Med 2021; 385: 2132-2139.
    Pubmed KoreaMed CrossRef

Vol.41 No.2 April 2024

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