key: cord-0964370-nn5pid72
authors: Ursini, Francesco; Ruscitti, Piero; Raimondo, Vincenzo; De Angelis, Rossella; Cacciapaglia, Fabio; Pigatto, Erika; Olivo, Domenico; Di Cola, Ilenia; Galluccio, Felice; Francioso, Francesca; Foti, Rosario; Tavoni, Antonio Gaetano; D’Angelo, Salvatore; Campochiaro, Corrado; Motta, Francesca; De Santis, Maria; Bilia, Silvia; Bruno, Caterina; De Luca, Giacomo; Visentini, Marcella; Ciaffi, Jacopo; Mancarella, Luana; Brusi, Veronica; D’Onghia, Martina; Cuomo, Giovanna; Fusaro, Enrico; Cipriani, Paola; Dagna, Lorenzo; Guiducci, Serena; Meliconi, Riccardo; Iannone, Florenzo; Iagnocco, Annamaria; Giacomelli, Roberto; Ferri, Clodoveo
title: Systemic syndromes of rheumatological interest with onset after COVID-19 vaccine administration: a report of 30 cases
date: 2022-01-29
journal: Clin Rheumatol
DOI: 10.1007/s10067-022-06078-2
sha: ca71b6805b62948adbe4a4b67aaccec074b2fb5e
doc_id: 964370
cord_uid: nn5pid72

nan

web, by anti-science and anti-vaccine movements, although accumulating real-life data [1] confirm the favorable safety profile already demonstrated in phase III clinical trials [2] .

It is interesting to note that despite the lack of a robust literature evidence [3] , the potential role of vaccines in promoting the development of autoimmunity continues to fascinate researchers. The theoretical basis of this association relies on the possibility of molecular mimicry between components of the vaccine and specific human proteins and the stimulation of aberrant immune responses by adjuvants contained in vaccines [4] .

According to the World Health Organization (WHO), adverse events (AEs) after immunization are defined as "any untoward medical occurrence which follows immunization, which does not necessarily have a causal relationship with the usage of the vaccine" [5] .

Regarding COVID-19 vaccines, AEs are usually mild and mainly restricted to injection site reactions. Interestingly, amongst systemic AEs, arthralgia is one of the most common [2] and only isolated cases [6] [7] [8] [9] of inflammatory rheumatic diseases developed after COVID-19 vaccine administration have been described to date.

To contribute to shed light on this field, in December 2020, we published a web-based survey form and invited all members of the "COVID-19 and autoimmune systemic diseases" collaborative research group to spontaneously submit cases of systemic syndromes of rheumatological interest with onset within four weeks from the administration of the first or second dose of one of the COVID-19 vaccines approved in Italy (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S), encountered during routine clinical practice since the beginning of the vaccination campaign in January 2021. Exclusion criteria were a past history of any autoimmune or inflammatory rheumatic disease.

Using this approach, we built a series of 30 individual cases (Table 1) reported by 16 centers belonging to our research network, including 12 (40%) patients with skin vasculitis (40%), four (13.3%) with undifferentiated connective tissue diseases (CTD), two (6.7%) with Sjögren's syndrome (SjS), one (3.3%) with very early systemic sclerosis (SSc), one (3.3%) with overlap CTD (scleromyositis), two (6.7%) with atypical acrosyndrome [10] , one (3.3%) with iperinflammatory syndrome, three (10%) with giant cell arteritis (GCA), two (6.7%) with Takayasu's arteritis (TAK), one (3.3%) with of small vessel vasculitis, and one (3.3%) with cryoglobulinemic vasculitis. Mean time from vaccine administration to clinical manifestations onset was 9 days (range 1-28); most patients 16 (53.3%) received the BNT162b2 vaccine.

After a median follow-up of four weeks, 21 (70%) patients achieved remission or improvement of disease activity according to clinical judgment; on the other hand, seven (23.3%) patients had ongoing active disease (one with skin vasculitis, one with undifferentiated CTD, one with scleromyositis, one with atypical acrosyndrome, one with GCA, one with small vessel vasculitis, and one with iperinflammatory syndrome), while three (10%) were lost at follow-up. Most patients (25 out of 30) were initially treated with glucocorticoids (GCs), alone or in combination with disease-modifying antirheumatic drugs (DMARDs), histamine receptor 1 antagonist (H1RA), non-steroidal antiinflammatory drugs (NSAIDs), intravenous immunoglobulin (IVIG), anakinra, or vasoactive drugs.

In conclusion, despite a clear cause-effect relationship is far to be ascertained, our data suggest that systemic diseases of rheumatological interest may occasionally develop in close temporal association with COVID-19 vaccine administration. Interestingly, 15 patients (50%) developed autoantibodies, suggesting that COVID-19 vaccines may potentially elicit transient or sustained autoimmunity in selected individuals.

However, even if we assume a direct causal relationship, the overall safety of COVID-19 vaccines remains unconcerned and the benefits of vaccination largely outweigh the minimal risks associated with such potential adverse events. 

Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting

Efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis of randomized clinical trials

Can Vaccination trigger autoimmune disorders? A meta-analysis

Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction

WHO) WHO. Immunization safety surveillance: guidelines for immunization programme managers on surveillance of adverse events following immunization

Reactive arthritis after COVID-19 vaccination

Arthritis of the left elbow joint after vaccination against SARS-CoV-2 infection

Multisystem inflammatory syndrome in an adult following the SARS-CoV-2 vaccine (MIS-V)

Spectrum of short-term inflammatory musculoskeletal manifestations after COVID-19 vaccine administration: a report of 66 cases

Isolated "puffy hands" following COVID-19: clue to a long-term capillary leakage syndrome?

Ethics approval The study complies with the Declaration of Helsinki. Written informed consent has been obtained from the subjects involved.Disclosures None.

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