Age: 68.0
Sex: M
Vaccine: FLUX
Symptoms: Viral test negative
Clinical narrative: Idiopathic mixed cryoglobulinemic vasculitis; Mixed Cryoglobulinemic Glomerulonephritis; Thrombocytopenia; This literature case was received on 20-Nov-2023 and concerned a 68-years-old male patient.  Mixed cryoglobulinemia is associated with viral infections such as hepatitis B or C virus, lymphoproliferative and autoimmune disorders. Influenza vaccine-induced cryoglobulinemia has been rarely reported. This is rare case of cryoglobulinemic vasculitis following influenza vaccination with new onset renal involvement.  The patient's concurrent conditions included atrial fibrillation and chorioretinopathy. The patient's historical vaccines included two annual influenza vaccines (Brand not specified) in 2020 and 2021, for unreported indication, with presentations of rash and edema following each vaccine. The patient's concomitant medications were not reported (see linked cases 202307278 and 20237277).  On an unspecified date in 2022, the patient was vaccinated with influenza vaccine (brand not specified; dose, anatomical location, route of administration and indication: not reported). The batch number was not reported.  On an unspecified date in 2022, an unspecified amount of time following annual influenza vaccine, the patient developed idiopathic mixed cryoglobulinemic vasculitis. In addition to the edema and rash, the patient had thrombocytopenia and a positive rheumatoid factor (RF). The patient's illness was self-limited, but evaluation had shown mixed cryoglobulins. A bone marrow biopsy was unremarkable and viral etiologies were negative. The patient received intravenous immunoglobulin (IVIG) with improvement of rash and platelet count, but his edema persisted.  On an unspecified date in 2022, soon after, he was readmitted and found to have acute kidney injury (AKI) with creatinine of 2.89 mg/dL (baseline 1.2 mg/dL), hematuria, proteinuria, and labs showing RF elevation and low complements. An evaluation for paraprotein revealed IgM kappa and IgA lambda paraproteins, with cryoglobulin elevation in polyclonal fashion including IgG, IgA, but predominately IgM. The patient received IVIG and creatinine improved. A kidney biopsy showed endocapillary proliferative glomerulonephritis with organized deposits, consistent with mixed-type cryoglobulinemic glomerulonephritis.  On an unspecified date in 2022, the patient was treated with rituximab infusions, resulting in improvement in cryoglobulins and complement levels and renal function, with creatinine at 1.46 mg/dL measured on an unspecified day in May 2023. Plasmapheresis was performed for rash from IVIG.   At the time of initial reporting, on 20-Nov-2023, the patient was recovering from the events 'caryoglobulinemic vasculitis', acute kidney injury and thrombocytopenia.  The reporter assessed the events of glomerulonephritis and cryoglobulinemic vasculitis to be related to influenza vaccine. 'Mixed cryoglobulinemic glomerulonephritis triggered by Influenza vaccination' and 'Influenza vaccine-induced cryoglobulinemia has been rarely reported. We present a rare case of cryoglobulinemic vasculitis following influenza vaccination with new onset renal involvement.' The reporter did not provide a causality assessment for the event of thrombocytopenia.  The event cryoglobulinemic vasculitis, acute kidney injury, and thrombocytopenia was considered to be medically significant by a Physician within Regulatory Authority.    In conclusion, the patient had a favorable outcome after rituximab, IVIG, and plasmapheresis for diagnosis of mixed cryoglobulinema triggered by the influenza vaccine, noting a reduction of cryoglobulins, improved renal function, and resolution of rash. Cryoglobulins can form as an immune response to infections though it is unclear why cryoglobulins are produced as a response to a vaccination. Understanding this novel association and interaction is important for prompt diagnosis and management.  This case is linked with cases 202307278 and 20237277 (the same literature article).  Company comment: A 68-year-old patient developed cryoglobulinemic vasculitis and mixed cryoglobulinemic glomerulonephritis, as well as thrombocytopenia an unknown amount of time after receiving the suspect product influenza vaccine. Based on the information provided by the author, it is suggested that cryoglobulinemia may be a consequence of the influenza vaccine, and the causality for all events, (cryoglobulinemic vasculitis, mixed cryoglobulinemic glomerulonephritis, and thrombocytopenia) is assessed as possibly related.; Reporter's Comments: Cryoglobulinemic glomerulonephritis triggered by influenza vaccination and influenza vaccine-induced cryoglobulinemia has been rarely reported. We present a rare case of cryoglobulinemic vasculitis following influenza vaccination with new onset renal involvement.; Sender's Comments: A 68-year-old patient developed cryoglobulinemic vasculitis and mixed cryoglobulinemic glomerulonephritis, as well as thrombocytopenia an unknown amount of time after receiving the suspect product influenza vaccine. Based on the information provided by the author, it is suggested that cryoglobulinemia may be a consequence of the influenza vaccine, and the causality for all events, (cryoglobulinemic vasculitis, mixed cryoglobulinemic glomerulonephritis, and thrombocytopenia) is assessed as possibly related.