Chien-Jung  Lu

CASE REPORT:
A 39-year-old woman noticed diplopia one week after she accepted the first dose of Pfizer– BioNTech COVID-19 vaccine. Diagnosis of ocular MG was made after investigation. Despite intravenous immunoglobulins, pyridostigmine and prednisolone therapy, she had no improvement until 10 days after treatment. She then rapidly improved, and almost fully recovered in the following 10 days. We had observed this patient for 8 months. After tapering off steroid, she remained stable to date, though she still suffered from transient diplopia on awakening.

DISCUSSION:
In this patient, causal relationship between the onset of MG and the Pfizer–BioNTech COVID-19 vaccine was established on the basis of the following criteria: (1) a temporal association between administration of the Pfizer– BioNTech COVID-19 vaccine and the onset of symptoms of ocular MG existed; (2) symptoms developed within one week of vaccine administration (causality is defined by the WHO as less than 28 days)(13); and (3) no other potential triggers, including infection or new medications, were identified. To the best of our knowledge, this case ought to be the first one of new-onset ocular MG caused by Pfizer– BioNTech COVID-19 vaccine in the world. Published literature verified both Oxford–AstraZeneca COVID-19 vaccines and Pfizer–BioNTech COVID-19 vaccines could precipitate new-onset MG or exacerbate pre-existing MG. In this report, we paid our attention to new-onset ocular MG. As of 25 June 2022, seven reports of new-onset MG caused by COVID-19 vaccines were found. Pfizer–BioNTech COVID-19 vaccines were related to 4 cases of new-onset generalized MG(5, 11, 12). Galassi et al reported a coincidental ocular MG triggered by Oxford–AstraZeneca COVID-19 vaccine in a patient with pre-existing subclinical MG(8). There were only 2 cases of new-onset ocular MG which were actually caused by COVID-19 vaccines, and both were precipitated by Oxford–AstraZeneca COVID-19 vaccines(4, 7). Huang et al(7) reported a 53-year-old man with new-onset MG 1 day after the first dose of Oxford–AstraZeneca COVID-19 vaccination. Mahr and his colleague(4) reported a 52-year- old man with new-onset MG 1 day after the second dose of Oxford–AstraZeneca COVID-19 vaccine. All those 3 reports of new-onset ocular MG clearly described their symptoms at the onset, but none mentioned their clinical course after the diagnoses were made. This patient’s symptom began 1 week after administration of Pfizer–BioNTech COVID-19 vaccine. After onset, disability rapidly got worse and soon reached the nadir within 10 days. Thereafter, patient had had no improvement (at the nadir) for 16 days despite treatment with IVIg, pyridostigmine and prednisolone. Ten days after treatment with prednisolone 40 mg every day, patient began having improvement, and got almost full recovery in the following 10 days (treated with prednisolone 30 mg per day at that time). Although she had no recurrence of ptosis or worsening of diplopia during the period of tapering drugs, she had paradoxical diplopia on awakening. This patient had maintained at this plateau state for 8 months, except mild worsening of diplopia when she was suffering COVID19 viral infection. We were still observing this patient when we were writing this case report. We were interested in clinical course because we once hypothesized if it was possible that the clinical course of vaccine-induced ocular MG was acute and monophasic, just as that of acute inflammatory demyelinating polyneuropathy. However, as 8 months had gone, she still had transient diplopia on awakening. Our hypothesis of acute monophasic course of illness became less likely; this vaccine-induced ocular MG could probably be a life-long iatrogenic disease. As we reviewed current literature, no article mentioned the clinical course of vaccine-induced ocular MG. We dared not to draw too assumptive conclusion from this case report, and we had to admit that this patient’s manifestation was identical to ocular MG that we had ever known. Although the pathology at the neuromuscular junction of ocular MG is not known to be distinct from generalized MG, there are several important and unique differences between them with regard to diagnosis and treatment. It is also uncertain why the disease stays localized to the extraocular muscles in patients with ocular MG. Distinguishing solely ocular myasthenia from generalized myasthenia soon after onset is challenging(1). Of patients presenting with ocular MG, two-thirds will go on to develop signs and symptoms of extremity weakness and other bulbar muscle weakness, while one-third will continue to have pure ocular MG. Most (78 percent) of those who will develop generalized MG will do so within the first year, and 94 percent will do so within three years(1, 14, 15). A normal SFEMG study may be helpful in stratifying risk of generalization. In one study of 37 patients with ocular MG followed for two years, 82 percent of those with normal SFEMG in the extensor digitorum communis persisted with isolated ocular MG, whereas 58 percent of those with an abnormal study developed generalized MG(16). To be or not to be vaccinated was a question for patients with autoimmune disorders(12, 17). Vaccination poses a question whether vaccines containing pathogenic antigens can increase the risk of flare or exacerbate autoimmunity in susceptible individuals. As with this patient, a new autoimmune disorder could be triggered by a COVID-19 vaccine if patient had already suffered rheumatological problems. However, as we learned from these case reports, the incidence of vaccine-induced ocular MG was very low. Current cohort studies still emphasized the protection benefit of vaccination in patient with autoimmune diseases(18-20).