Funding/financial disclosures. The authors have no conflict of interest relevant to the content of this letter. No funding was received for the preparation of this letter.

Innov Clin Neurosci. 2022;19(7–9):8.

 

Dear Editor:

We report the case of a 70-year-old patient affected by ocular myasthenia gravis (MG), diagnosed three years ago due to double vision and drooping left eyelid, who was responsive to low-dose of steroids (prednisone 12.5mg/day). When he required COVID-19 vaccination, the general practitioner suggested that he stop prednisone administration three days before and two days after the first dose of the Pfizer-BioNTech vaccine. 

During the days he stopped taking prednisone, the patient complained of progressively worsening diplopia, and he made a neurological telemedicine consultation. Steroids were gradually reintroduced up to the initial dosage, and he experienced diplopia resolution. At the second dose of the Pfizer-BioNTech vaccine, the patient did not interrupt steroids and had no neuromuscular symptoms. 

There are no data available on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies generated after vaccination in this case report, since the patient preferred to avoid public crowds, in line with the International MG/COVID-19 working group guidelines.1 MG is an antibody-mediated neuromuscular junction disorder.2 Autoantibodies involved are typically those against the acetylcholine receptors (AChRs); less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and agrin.2 MG symptoms can include fluctuating ocular, bulbar, respiratory, and limb muscle weakness.2 MG management includes the use of cholinesterase enzyme inhibitors and immunosuppressive agents, such as steroids (e.g., prednisone, prednisolone, and methylprednisolone).3 

With the approval of COVID-19 vaccines, there are new issues relating to the management of steroidal therapy in patients with MG due to potential interactions with vaccine efficacy.2 Specifically, considering the Pfizer-BioNTech clinical trial data, patients with autoimmune diseases receiving immunosuppressants (i.e., systemic corticosteroids) were excluded. Similar patient exclusion occurred in the Moderna clinical trial data, where patients receiving corticosteroids at a dose of 20mg or higher per day within six months before vaccination were excluded.2 The major concern regarding COVID-19 vaccines in patients with MG on steroidal therapy is vaccine efficacy, since the corticosteroids might interfere with critical components of vaccine-based immunity, such as antigen presentation, T/B cell function, and antibody generation.4 

In this case, due to the rapid clinical worsening after steroid withdrawal, we speculate that the patient’s steroid therapy was underdosed to manage MG symptoms. COVID-19 vaccination might have triggered an autoimmune system response, exacerbating MG activity. 

To date, there are no data regarding MG exacerbation risk by the COVID-19 vaccine; moreover, the safety and efficacy of COVID-19 messenger ribonucleic acid (mRNA) vaccines in patients with MG on steroid therapy is under investigation.5 Given the lack of direct evidence supporting COVID-19 vaccine efficacy in combination with these therapies, it might be reasonable for clinicians to consider individual patient risks related to steroidal reduction, since it can lead to worsening of MG and myasthenic crisis. However, it is not recommended to avoid vaccination, since the COVID-19 clinical picture might induce a severe coagulopathy and systemic multiorgan failure disease that could worsen myasthenic symptoms.

References

  1. International MG/COVID-19 Working Group, Jacob S, Muppidi S, et al. Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic. J Neurol Sci. 2020;412:116803. 
  2. Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations. J Clin Med. 2021;10(11):2235.
  3. United States National Library of Medicine. A study of Ad26.COV2.S for the prevention of SARS-CoV-2-mediated COVID-19 in adult participants (ENSEMBLE). 2020. https://clinicaltrials.gov/ct2/show/NCT04505722. Accessed 13 Jan 2021.
  4. Saxon A, Stevens RH, Ramer SJ, et al. Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis. J Clin Invest. 1978;61(4):922–930. 
  5. McClung N, Chamberland M, Kinlaw K, et al. The advisory committee on immunization practices’ ethical principles for allocating initial supplies of COVID-19 vaccine—United States, 2020. Morb Mortal Wkly Rep. 2020;69:1782–1786. 

With regards,

Angelo Alito, MD; Carmelo Rodolico, MD; Michelangelo Palco, MD; and Simona Portaro, MD, PhD 

Drs. Alito and Portaro are with the Unit of Physical and Rehabilitative Medicine, Policlinico G. Martino in Messina, Italy. Prof. Rodolico is with the Clinical and Experimental Medicine Department, University of Messina in Messina, Italy. Dr. Palco is with the Section of Orthopedics and Traumatology, University of Messina in Messina, Italy.