Recurrent Mixed Cryoglobulinemic Vasculitis After Influenza Immunization

October 6, 2026

Annals Of Internal Medicine: Clinical Cases

Overview

An 83-year-old man developed type II mixed cryoglobulinemic vasculitis with lower-extremity purpura and acute kidney injury on two occasions, each occurring one week after influenza vaccination. Evaluation did not identify another cause; the recurrence and timing suggest a possible vaccine association, while renal function remained impaired despite clinical and serologic remission.

Background

Mixed cryoglobulinemic vasculitis is a small-vessel vasculitis commonly associated with chronic viral infection, autoimmune disease, or lymphoproliferative disorders. It can involve the skin and kidneys, among other organ systems. Vaccine-associated cases have been reported rarely, and the source describes influenza vaccination-associated disease as exceedingly uncommon. Identifying an underlying cause is relevant to evaluating patients with cryoglobulinemic vasculitis.

Data Highlights

Finding	First episode	Second episode and follow-up
Timing relative to influenza vaccination	1 week	1 week
Creatinine during episode	1.47 mg/dL (baseline 1.0 mg/dL)	2.60 mg/dL
Cryoglobulin findings	Cryocrit 2%; immunofixation showed monoclonal IgM and polyclonal IgG	Repeat evaluation supported mixed cryoglobulinemic vasculitis; cryoglobulins were undetectable 3 months after treatment
Other laboratory findings	Rheumatoid factor >650 IU/mL; C3 80 mg/dL; C4 <2.0 mg/dL	Transient PR3-ANCA positivity; complement normalized and PR3-ANCA became negative after treatment
Renal outcome	Acute kidney injury with hematuria and proteinuria	Biopsy showed no immune complex–mediated glomerular disease or ANCA-associated crescentic glomerulonephritis; creatinine stabilized at approximately 2.0–2.4 mg/dL, with eGFR 30 mL/min/1.73 m²

Key Findings

Skin biopsy showed leukocytoclastic vasculitis, and cryoprecipitate immunofixation demonstrated monoclonal IgM with polyclonal IgG, establishing type II cryoglobulinemic vasculitis.
The initial episode included bilateral lower-leg purpura, acute kidney injury, hematuria, proteinuria, markedly elevated rheumatoid factor, and low complement.
Testing for hepatitis B and C, HIV, autoimmune disease, lymphoproliferative disorders, and malignancy did not identify an alternative etiology.
A nearly identical episode occurred one year later, again one week after influenza vaccination, with creatinine increased to 2.60 mg/dL and newly detected PR3-ANCA.
After prednisone treatment, the rash resolved and follow-up testing showed undetectable cryoglobulins, normalized complement, and negative PR3-ANCA; creatinine did not return to baseline.
Renal biopsy approximately one year after the second hospitalization showed acute tubular injury, diffuse diabetic glomerulosclerosis, tubular atrophy and interstitial fibrosis, without immune complex–mediated glomerular disease or ANCA-associated crescentic glomerulonephritis.

Conclusion

This case describes recurrent type II mixed cryoglobulinemic vasculitis occurring one week after influenza vaccination on two occasions, with no alternative cause identified. The temporal recurrence suggests a possible association, while the report does not establish causality.