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| LETTER TO EDITOR |
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| Ahead of print publication |
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The emergence of rheumatic immune-mediated inflammatory disease manifestations following SARS-CoV-2 vaccination
Arvind Nune1, Hem Raj Sapkota2, Karthikeyan P Iyengar3
1 Department of Rheumatology, Southport and Ormskirk Hospital NHS Trust, Southport, Wolverhampton, UK
2 Department of Trauma and Orthopaedics, Southport and Ormskirk Hospital NHS Trust, Southport, Wolverhampton, UK
3 Department of Rheumatology, The Royal Wolverhampton Hospital NHS Trust, Wolverhampton, UK
| Date of Submission | 30-Jun-2021 |
| Date of Acceptance | 25-Aug-2021 |
| Date of Web Publication | 22-Jan-2022 |
Correspondence Address:
Arvind Nune,
Southport and Ormskirk NHS Trust, Southport
UK
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/injr.injr_145_21
Dear Editor,
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are deemed safe and effective, but there is increasing attention on Adverse Events Following Immunization (AEFI). Rheumatic manifestations after COVID-19 vaccinations are not well known.
We highlight two cases of Systemic Autoimmune Rheumatic Disease following the SARS-CoV-2 vaccinations displaying new-onset Rheumatic Immune-Mediated Inflammatory Disease. Both patients had no preceding COVID-19 infection and had a negative SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction.
Our first case is a 70-year-old Caucasian woman with Type-2 diabetes mellitus, who presented with a sore left arm 4 days following her Pfizer/BioNTech m-RNA SARS-CoV-2 vaccination in February 2021. Symptoms progressed over a few days, with pain and early morning stiffness lasting for a few hours around the shoulders, neck, hips, and lower back. Inflammatory markers were raised with a C-reactive protein (CRP) of 88 mg/L (normal range 0–4) and an erythrocyte sedimentation rate (ESR) of 114 mm/h. The patient was commenced on oral prednisolone 20 mg a day for a suspected diagnosis of polymyalgia rheumatica (PMR), which improved her symptoms. Subsequently, her CRP improved to 16 mg/L and ESR to 35 mm/h. She remains clinically stable as the prednisolone dose is being tapered.
Our second case is of a 44-year-old Caucasian lady who developed a painful and swollen right ankle on day two after the AstraZeneca-Oxford vaccination in March 2021. Her CRP was raised at 78 mg/L with negative anticyclic citrullinated peptide antibodies, rheumatoid factor, and serum urate. Having failed on naproxen 500 mg twice a day for a week, she was commenced on prednisolone 15 mg a day for 3 weeks. She reported recurrence of symptoms in the right ankle when steroids were discontinued, whilst her left ankle symptoms remained settled. The patient continues to improve on a tapering dose of prednisolone and CRP of 13 mg/L.
A diagnosis of reactive arthritis post-SARS-CoV-2 vaccination was considered the most likely explanation of acute onset synovitis affecting both of her ankles.
Molecular mimicry, bystander activation, epitope spreading, polyclonal activation of B cells, and vaccine-triggered autoimmunity have been suggested as mechanisms of these AEFI.[1],[2] Concerns have been raised recently developing an acute auto-immune response in individuals undergoing vaccination against SARS-CoV-2 spike glycoproteins.[3] This has been seen, particularly in genetically susceptible individuals, through cross-reactivity with host cells.[4] Immune cross-reaction to components that stabilize the vaccines and the use of adjuvants could also play a role in the autoimmune processes after SARS CoV-2 vaccinations.[5]
PMR is relatively common in Caucasians with an incidence rate of 95.9 per 100,000 in the UK; therefore, the association may not necessarily imply causation. However, reactive arthritis is relatively uncommon in this part of the world which supports our view to exploring the possibility of vaccine-triggered autoimmunity. Our patients were well and had no symptoms for rheumatic autoimmune conditions before receiving SARS CoV-2 vaccinations. Asymptomatic SARS-CoV-2 infection causing rheumatic manifestations is also a potential possibility. However, we had not checked the SARS-CoV-2 antibody test. Long-term longitudinal studies may shed greater light on this hypothesis and strengthen surveillance of the global vaccination program to reveal the true extent of autoimmune manifestations following SARS-CoV-2 vaccination.
Patient consent
Obtained appropriate consent.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Vadalà M, Poddighe D, Laurino C, Palmieri B. Vaccination and autoimmune diseases: Is prevention of adverse health effects on the horizon? EPMA J 2017;8:295-311.  |
| 2. | De Martino M, Chiappini E, Galli L. Vaccines and autoimmunity. Int J Immunopathol Pharmacol 2013;26:283-90. |
| 3. | Mahase E. Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ 2020;371:m4347. |
| 4. | Caso F, Costa L, Ruscitti P, Navarini L, Del Puente A, Giacomelli R, et al. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmun Rev 2020;19:102524. |
| 5. | Segal Y, Shoenfeld Y. Vaccine-induced autoimmunity: The role of molecular mimicry and immune crossreaction. Cell Mol Immunol 2018;15:586-94. |
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