Recurrent Mixed Cryoglobulinemic Vasculitis After Influenza Immunization

October 6, 2026

Annals Of Internal Medicine: Clinical Cases

At a Glance

Category	Detail
Condition	Type II mixed cryoglobulinemic small-vessel vasculitis temporally associated with influenza vaccination
Key Mechanisms	The mechanism is unclear. The authors propose vaccination may act as an antigenic trigger in a patient with a possible low-level clonal B-cell population.
Target Population	The report describes an 83-year-old man with recurrent lower-extremity purpura and acute kidney injury; it does not establish a broader at-risk population.
Care Setting	Hospital evaluation and follow-up of suspected cryoglobulinemic vasculitis with skin and renal involvement.

Key Highlights

The patient had two similar episodes of bilateral lower-extremity purpura and acute kidney injury, each occurring one week after influenza vaccination.
Type II cryoglobulinemic vasculitis was supported by skin biopsy and cryoprecipitate immunofixation showing monoclonal IgM and polyclonal IgG.
Evaluation for viral infection, autoimmune disease, lymphoproliferative disorders, and malignancy did not identify an alternative cause.
The authors state that vaccine-associated cryoglobulinemic vasculitis is exceedingly uncommon and that the mechanism remains unclear.
Renal biopsy showed acute tubular injury and diffuse diabetic glomerulosclerosis, without immune complex–mediated glomerular disease or ANCA-associated crescentic glomerulonephritis.

Guideline-Based Recommendations

Diagnosis

In suspected cryoglobulinemic vasculitis, the reported evaluation included skin biopsy, serum cryoglobulin testing, and cryoprecipitate immunofixation.
The authors advise considering vaccine-associated vasculitis when no other explanation is apparent, after excluding more typical causes such as chronic viral infection, autoimmune disease, and hematologic conditions.

Management

In this case, the first episode improved after a single 40-mg oral prednisone dose that was stopped after shared decision making.
The recurrent episode was treated with oral prednisone 40 mg followed by a taper; the patient improved gradually.

Monitoring & Follow-up

Follow-up after treatment documented rash resolution, undetectable serum cryoglobulins, normalized complement levels, and negative PR3-ANCA.
Persistent renal dysfunction prompted renal biopsy; kidney function later stabilized at a creatinine of approximately 2.0–2.4 mg/dL.

Risks

The case involved acute kidney injury with hematuria and proteinuria, and renal function did not return to baseline.
The authors note that a low-level B-cell clone may not be detected by serum protein electrophoresis; cryoprecipitate immunofixation may identify small IgM paraproteins.

Patient & Prescribing Data

One 83-year-old man with congestive heart failure, coronary artery disease, peripheral arterial disease, and type II diabetes mellitus; the report does not provide population-level prescribing data.

Prednisone was used during both episodes: one 40-mg dose during the first episode and 40 mg followed by a taper during the second. The first rash improved without further intervention.

Clinical Best Practices

Assess for common secondary causes of mixed cryoglobulinemic vasculitis, including chronic viral infection, autoimmune disease, and hematologic disorders.
Interpret serum protein electrophoresis cautiously: the authors note that a negative result does not exclude a low-level B-cell clone.
Consider renal biopsy when renal dysfunction persists; in this case, biopsy excluded immune complex–mediated glomerular disease and ANCA-associated crescentic glomerulonephritis.