Despite the increased medication, he continued to have clinically significant symptoms, so we asked him to come to our clinic for an ultrasound evaluation. He took ibuprofen and prednisone 5 mg soon after the pain and swelling began, but his symptoms persisted, so he contacted our office the next day and we advised him to increase his prednisone to 10 mg daily. He had no other joint pain, swelling, or stiffness. He received the second vaccine dose on Jan 13, 2021, and within 12 h developed clinically significant pain and swelling in the right knee. He received the first BNT162b2 vaccine on Dec 23, 2020, after which he developed minor arthralgias that resolved within 1 day. The patient had no known exposures to SARS-CoV-2 and had tested negative for SARS-CoV-2 by PCR in April, 2020, when screened for work. At his last clinic visit in September, 2020, his physical exam showed no active synovitis or joint effusions, and his disease activity scores were consistent with remission (clinical disease activity index=0 disease activity score of 28 joints with C-reactive protein=1♲1).
The patient had been in clinical remission on upadacitinib monotherapy since July, 2018. Here, we present a case of a White male, aged 55 years, with non-erosive, seropositive rheumatoid arthritis (positive for rheumatoid factor, anticyclic citrullinated peptide antibodies, antinuclear antibodies, and anti-Ro antibodies) who had been in sustained clinical remission for more than 2 years and developed an acute flare of his rheumatoid arthritis 12 h after the second BNT162b2 vaccination. 8 The American College of Rheumatology issued guidance regarding COVID-19 vaccination on Feb 8, 2021, and acknowledged a theoretical risk of flare of autoimmune disease after vaccination with moderate consensus. 7 Molecular mimicry is thought to be one mechanism by which autoimmunity can occur, in which similarities between viral peptides and self-peptides can stimulate immune activation, but this has not been proven in rheumatoid arthritis. There are reports of other vaccines, such as those against tetanus, rubella, hepatitis B, and influenza, triggering rheumatoid arthritis, but causality has never been proven and an association has never been reproduced in large, controlled studies. 5, 6 Therefore, it is not fully known whether these vaccines might provoke flares of underlying rheumatic conditions as a result of immune activation or non-specific adjuvant effects. The clinical trials of these vaccines allowed for patients with rheumatic disease to participate in the later stages of the trials, but excluded patients on immunosuppressive agents. 4 Two of the vaccines, BNT162b2 (BioNTech-Pfizer) and mRNA-1273 (Moderna), are novel mRNA-based vaccines delivered via lipid nanoparticles. Three COVID-19 vaccines have been approved for emergency use in the USA so far. 1, 2 A review of the literature shows there has been one case report so far of a flare of rheumatoid arthritis after infection with SARS-CoV-2. With the COVID-19 pandemic, there has been great uncertainty about whether the virus could exacerbate autoimmune diseases such as rheumatoid arthritis given that infection can lead to an overactivation of the immune system, which is thought to play a part in severe cases in the general population.
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