Discussion and Conclusions
IIMs are a group of conditions that include dermatomyositis, polymyositis, and immune-mediated necrotizing myopathy. They share common clinical features such as muscle weakness and inflammation, skin disease, or other organ-specific manifestations. Variation in extramuscular findings, serology, and biopsy results differentiates one condition from another.
At present, there is only one reported case of SARS-CoV-2 vaccine-related IIM, where the myositis was localized to the location of intramuscular injection. The patient was managed conservatively without any immunosuppressants. The authors postulated that in addition to the minor muscle injury from injection, there were unknown mechanisms driving the inflammatory process. In our cases, the myositis was systemic and severe, and both patients required and responded well to corticosteroid and immunoglobulin therapy.
Without more cases and convincing pathophysiology, it is not possible to conclude that our patients developed inflammatory myopathy because of the SARS-CoV-2 vaccine, especially in Patient B who might have developed myositis as a paraneoplastic complication of pancreatic malignancy, a well-recognized association. It is also possible that both patients were predisposed to autoimmune disease, whether from preexisting cancer or otherwise, and the vaccine provided the final necessary stimulus to propagate the cascade of autoimmunity to manifest in clinical disease. Regardless, the timing of the disease onset shortly after the vaccine administration and the lack of previous history and family history of autoimmune disorders raise an important question of this novel mRNA therapy.
There are a few proposed mechanisms in drug-induced myopathy: direct myotoxicity, indirect muscle damage, and immunologically related inflammation. Drugs that directly cause myotoxicity, such as glucocorticoids, accumulate in muscle tissues and damage them, while others can indirectly damage tissue by inducing hyperthermia or hyperkinesis. If there is a causal link between mRNA vaccines and IIMs, the process is likely immunological since mRNA and lipid vector are not known to damage muscle tissues directly or indirectly. Cases of immunologically related drug-induced myopathy have been reported in immune checkpoint inhibitors and interferon-alpha, although the precise mechanisms are not elucidated.
SARS-CoV-2 infection itself has been associated with autoimmune conditions such as pediatric inflammatory multisystemic syndrome and Guillain–Barré syndrome. Furthermore, a recent study in dermatomyositis patients identifies three T cell receptor epitopes specific to SARS-CoV-2 (O-ribose methyltransferase, RNA-dependent RNA polymerase, and 3'-to-5' exonuclease proteins), suggesting a potential for the virus to contribute to myositis development. mRNA vaccines, which contain a genetic blueprint for SARS-CoV-2 spike protein, may therefore trigger a similar process. Theoretically, mRNA may bind to pattern recognition receptors prior to translation, be recognized by Toll-like receptors and activate pro-inflammatory cascade including type I interferon response, which is linked to dermatomyositis. In other cases of vaccine-related autoimmune diseases such as the A/New Jersey influenza vaccine and Guillain–Barré syndrome, it is postulated that molecular mimicry or genetic susceptibility are responsible for this association, however, none has been proven.
A recent review article discusses various neurological autoimmune disorders encountered within 1–4 weeks of SARS-CoV-2 vaccination. These included demyelinating disease, inflammatory peripheral neuropathies, and two patients with de novo inflammatory myositis. Similar to our two patients here, both cases were female, and both required corticosteroid therapy and improved with immunosuppression. The authors concluded that the incidence of these autoimmune events were low, patient outcomes were favorable, and the benefits of vaccination outweighed the comparatively small risks.
Indeed, in this report, we described two cases of IIMs that developed shortly after receiving the BNT162b2 vaccine. However, without more robust evidence, it is not possible to conclude that there is a causal relationship between the two. Furthermore, even if there was an association between IIM and SARS-CoV-2 vaccine, the risk is extremely small given that there were over 617,000 people who received at least one dose of the vaccine in the boroughs covered by our hospital at the time, translating to 1 case in 308,000 individuals. In contrast, SARS-CoV-2 has infected over 170 million people and caused 3.5 million deaths globally, highlighting the drastic benefits of the vaccine over its potential harm. Hence, mRNA vaccines against SARS-CoV-2 are widely considered to be safe and effective and should be encouraged to tackle this global pandemic.
COVID-19: Coronavirus disease 2019; SARS-Cov-2: Severe acute respiratory syndrome coronavirus 2; mRNA: Messenger ribonucleic acid; IIM: Idiopathic inflammatory myopathy; MRC: Medical Research Council; CK: Creatine kinase; CT: Computed tomography; IVIG: Intravenous immunoglobulin.
The authors have no sources of funding to declare.
Availability of data and materials
The datasets used during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
As this is a case report regarding standard practice and consent was obtained from both patients, advice was sought and ethical approval for this report was deemed not necessary.
Consent for publication
Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
J Med Case Reports. 2022;16(57) © 2022 BioMed Central, Ltd.