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In the past months, mass vaccination represented the turning point of the global battle against the COVID-19 pandemic, an unprecedented challenge for physicians, healthcare professionals, health systems and pharmaceutical companies. More than 6 billion doses of vaccine have been administered to date, covering nearly 50% of the world’s population. Although the vaccination campaign is still thwarted by spread of fake news disseminated by a ubiquitous antivaxxer movement, accumulating real-life data1 confirm the favourable safety profile already demonstrated in phase III clinical trials.2
Despite the lack of a steady literature evidence,3 the potential role of vaccines in promoting autoimmunity continues to intrigue many researchers. The theoretical basis of this association relies on the possible molecular mimicry between macromolecular components of the vaccine and specific human proteins and the exuberant immune response elicited by adjuvants contained in vaccines.4
Adverse events (AEs) associated with COVID-19 vaccines are usually mild and mainly restricted to injection site reactions. Interestingly, among systemic AEs, arthralgia is one of the most common.2 To the best of our knowledge, only isolated cases5 of arthritis developed after COVID-19 vaccine administration has been described; however, in a recently published survey including 1377 participants with rheumatic diseases, 11% of the respondents reported flare requiring treatment following injection of mRNA-based vaccines.6
The ‘COVID-19 and Autoimmune Systemic Diseases’ is a collaborative network of Italian rheumatologists, equally distributed across the country, spontaneously born in response to the COVID-19 pandemic with the aim to contribute to the advancing knowledge about COVID-19 and rheumatic diseases, by providing real-life data obtained from participating centres. To date, more than 60 rheumatologists from 40 different rheumatology clinics are affiliated to the study group.
In December 2020, we published a web-based survey form and invited all members of the study group to inform cases of inflammatory musculoskeletal manifestations (eg, synovitis, tenosynovitis, enthesitis, inflammatory spinal pain or girdles pain/stiffness with serological evidence of inflammation) with onset within 4 weeks from the administration of the first or second dose of one of the COVID-19 vaccines approved in Italy (BNT162b2, mRNA-1273, AZD1222 and Ad26.COV2.S), prospectively encountered during routine clinical practice since the beginning of the vaccination campaign, in January 2021, and up to August 31, 2021. Exclusion criteria were a history of any inflammatory rheumatic disease, isolated arthralgia/myalgia without clear evidence of inflammation, or vague and/or non-specific musculoskeletal complaints. Written informed consent was obtained from all patients.
By using this approach, we built a case series comprising 66 individual patients reported by 16 different rheumatology centres; most of them (59%) received the BNT162b2 vaccine. The average delay between the day of the ‘trigger’ injection (44.4% coinciding with the first dose) and arthritis onset was 11–13 days.
Stratification according to the predominant pattern of involvement at presentation (table 1) revealed that girdles pain/stiffness with acute-phase reactant elevation resembling polymyalgia rheumatica (PMR-like) was the most common (41%) clinical picture followed by oligoarthritis (32%) and polyarthritis (27%). Polyarticular and PMR-like cases were mainly symmetric (83% and 89%, respectively); involvement of small joints and tenosynovitis (39%) were significantly more frequent in polyarthritic forms (61% and 39%, respectively), while enthesitis was more common in oligoarthritic presentation (14%). Of note, two patients (one in the polyarticular group and one in the oligoarticular group, respectively) had also inflammatory back pain with evidence of active sacroiliitis and/or spondylitis on MRI. Detection of autoantibodies in sera was an uncommon finding; HLA-B27 status was obtained in only 21 (31.8%) patients, of which one in the polyarthritis subgroup tested positive.
Most patients were treated with glucocorticoids (50%–78%), non-steroidal anti-inflammatory drugs (33%–52%) or analgesics (14%–28%), while disease-modifying antirheumatic drugs were used in five (28%) patients with polyarthritis, five (24%) patients with oligoarthritis and only three (11%) patients with PMR-like presentation.
Despite the limitation of a very short follow-up, the clinical course seemed excellent in patients with PMR-like onset with 74% achieving full remission of symptoms after 2 weeks; on the other hand, 67% of patients with polyarthritis had active disease after an average follow-up of 6 weeks.
In conclusion, despite the fact that a clear cause–effect relationship is far to be ascertained, our data suggest that inflammatory musculoskeletal symptoms may occasionally develop in close temporal association with COVID-19 vaccine administration. However, even assuming a direct causal relationship, we feel that the overall safety of COVID-19 vaccines remains unaffected, and the benefits of vaccination largely outweigh the minimal risks associated with such uncommon inflammatory complications, probably reflecting a transient reactogenic response to the vaccine rather than a structured, chronic inflammatory joint disease.
Patient consent for publication
Handling editor Josef S Smolen
Contributors FU and CF designed the study, analysed the results and prepared the first draft of the letter. All the other authors contributed to the data collection and critical revision of the draft.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.