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Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2
  1. Marcella Visentini1,
  2. Laura Gragnani2,
  3. Stefano Angelo Santini3,4,
  4. Teresa Urraro5,
  5. Annalisa Villa1,
  6. Monica Monti2,
  7. Andrea Palladino1,
  8. Luisa Petraccia2,
  9. Francesca La Gualana1,
  10. Serena Lorini2,
  11. Silvia Marri2,
  12. Francesco Madia2,
  13. Lucia Stefanini1,
  14. Stefania Basili1,
  15. Massimo Fiorilli1,
  16. Clodoveo Ferri6,7,
  17. Anna Linda Zignego2,
  18. Milvia Casato1
  1. 1 Department of Translational and Precision Medicine, University of Rome La Sapienza, Rome, Italy
  2. 2 MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy
  3. 3 Department of Basic, Clinical, Intensive and Perioperative Biotechnological Sciences, Catholic University School of Medicine, Rome, Italy
  4. 4 Synlab Italia, Monza, Italy
  5. 5 Rheumatology Unit, M Scarlato Hospital, Scafati, Italy
  6. 6 Rheumatology Unit, Universita degli Studi di Modena e Reggio Emilia, Modena, Italy
  7. 7 Rheumatology Unit, Madonna dello Scoglio Hospital, Cotronei, Italy
  1. Correspondence to Dr Marcella Visentini, Department of Translational and Precision Medicine, University of Rome La Sapienza, 00185 Rome, Lazio, Italy; marcella.visentini{at}

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Studies on the safety and immunogenicity of SARS-CoV-2 vaccination in patients with inflammatory rheumatic diseases have so far not included mixed cryoglobulinaemia (MC) vasculitis.1–3 We report a prospective observational multicentre study on this disorder.

Participants were followed at four tertiary referral centres and were instructed to promptly inform the attending physicians about unusual events felt as possibly related to vaccination. Seventy-one patients were recruited: they had infection-cured hepatitis C virus (HCV)-related MC, either uncomplicated (HCV-MC, n=50) or complicated by low-grade non-Hodgkin’s lymphoma (MC-NHL, n=8), or essential MC (EMC, n=13). The characteristics of the patients, exclusion criteria and definition of bona fide vaccination-related flare are described in online supplemental methods.

Supplemental material


Overall, 9 of 71 (12.7%) patients had postvaccination MC vasculitis flare. However, 8 of 71 patients had experienced within 12 months before vaccination spontaneous flares, where 7 cases required rituximab and 3 of them (37.5%) had postvaccination flare (see online supplemental information). Thus, to exclude the confounding effects of high proneness to spontaneous flare as the facilitator and of rituximab as the preventor, we further restricted the evaluation of postvaccination flare rate to 63 patients off-therapy and without spontaneous flares for 20–48 months before …

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  • Handling editor Josef S Smolen

  • Contributors MV and LG contributed equally to this paper. Study design: MV, LG, MF, CF, ALZ, MC. Sample collection: LG, TU, MM, LP, SL, SM, FM. Experiments and data analysis: SAS, AV, AP, FLG. Tables and figures: MV, MF. Data interpretation: MV, LG, SAS, LS, SB, MF, CF, ALZ, MC. Writing of the manuscript: MV, MF, MC. Critical proof-reading of the manuscript: all authors.

  • Funding The study was funded by the Sapienza University Intramural Research Programme (grants RM11916B7567F9E4 and RM120172B8BE02DA) and by department funds of the centres participating in the study.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.