Relapse of cryoglobulinemic vasculitis with new-onset severe renal involvement in two patients following mRNA COVID-19 vaccination

Abstract

Rationale: Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination. Patient concerns: The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively. Diagnosis: Kidney biopsies were performed. The first pacient's kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient's kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury. Interventions: Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period. Outcomes: Clinical and immunological response was achieved in both patients after four months of follow-up. Lessons: The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization.

Cold case: COVID-19-triggered type 1 cryoglobulinemia

“…[9] Additionally, two patients with Sjögren's syndrome with relapsed type II cryoglobulinemic vasculitis with new onset renal involvement upon SARS-Cov2 mRNA vaccination were described. Also here, no data were available upon the type of cryoglobulin before and after SARS-CoV-2 mRNA vaccination, neither on speci city testing of the cryoprecipitate raising the question whether these cryoglobulins are SARS-Cov-2 speci c. [10] Our case highlights the appearance of a type I cryoglobulinemia triggered by COVID-19. The determination of the cryoglobulinemia as type I (i.e., monoclonal) renders this case unique, because cryoglobulinemia secondary to infection is usually a type II or III (i.e., polyclonal).…”

Vasculitic flare in a patient with anti-myelin-associated glycoprotein (MAG) antibody following mRNA-1273 SARS-CoV-2 vaccine

“…Relapse of cryoglobulins vasculitis [9,15] or other autoimmune diseases [7,11] after SARS-COV-2 vaccines have already been described. Although autoimmune diseases seem more commonly triggered after adenovirus vectored SARS-CoV-2 vaccines [8], also mRNA vaccines, stimulating the immune system, may worsen autoimmune diseases [7,9,11,15]. However mRNA vaccine for SARS-COV-2 is recommended in cryoglobulinemic vasculitis being the benefit/risk in favor of vaccination [10].…”

COVID-19 Vaccination and New Onset Glomerular Disease: Results from the IRocGN2 International Registry

“…The majority did not have proteinuria at baseline (Supplementary Table S2). At biopsy, overall median proteinuria (g/g) was 4 [2][3][4][5][6][7][8][9] which decreased to 1 [0-4], p<0.001) by follow up (Figure 2A). "Persistent proteinuria" was reported in 16% of patients (Table 5) after mean follow-up of 120 ±109 days.…”

“…Reports of de novo and relapses of glomerular disease (GD) temporally associated with COVID-19 vaccination (termed CVAGD for COVID-19 vaccine–associated GD) began to emerge by mid-2021 with an increasing number of reports published. 2-27 To date, a cause-effect relationship has not been established. Given the relative rarity of these events and limited follow-up, we created an International Registry of COVID-19 vaccination and Glomerulonephritis to collect consistent data on potential cases of CVAGD to analyze in aggregate.…”