Sex: M
Vaccine: FLUX, PPV
Symptoms: Urine analysis normal
Clinical narrative: Type II mixed cryoglobulinemia; This literature marketed report has been received from the authors of the published article, titled as stated below concerning a 76 year old male patient. The patient's pertinent medical history included a bypass surgery. His concurrent conditions included coronary artery disease, hypercholesterolemia and gastroesophageal reflux disease. The patient's concomitant medications were not reported.   On an unspecified date, the patient was vaccinated with pneumococcal vaccine, polyvalent (23-valent)(manufacturer unknown) and with influenza virus vaccine (unspecified) both for prophylaxis (strength, dose, dose number, route of administration, lot number and expiration date were not reported).   On an unspecified date, five days after vaccination, the patient presented with flu-like symptoms and cyanosis of the toes and fingers. He also had nonpalpable, purpuric lesions on his toes and fingers along with acral pain. It was also reported that he progressively had worsening purpura and digital ischemia along with livedo reticularis of both plantar surfaces. Within four weeks, the patient presented anorexia, night sweats, myalgias, fatigue and arthralgias. A biopsy was offered but the patient refused to do it.   On an unspecified date, the patient had laboratory evaluation with normal findings of complete blood count, urinalysis, comprehensive metabolic panel, he also had antinuclear antibodies, antineutrophil cytoplasmatic antibodies, anticardiolipin antibodies, immunofixation eletrophoresis, hepatitis A antibody, hepatitis B surface antigen and hepatitis C antibody tests and all of them with negative results. The patient had additional tests that included rheumatoid factor at 24 IU/mL, total hemolytic complement level (CH50) at 28 (units not provided), C3 level at 75.50 mg/dL, C4 level at 1.67 mg/dL, Westergren erythrocycte sedimentation rate at 48 mm/h, high sensitive C-reactive protein at 5.24 mg/dL, antiphosphatidylserine IgG at 19 (units not provided) and antiphosphatidylserine IgM at 64 (units not provided). The patient had also a chest radiograph and doppler studies of blood flow of the extremities that were also normal. Additionally, the patient had an initial cryoglobulins test that was negative. Two weeks later, the patient had his rheumatoid factor measured and it was 54 IU/mL.  The patient then started treatment with oral prednisone 20mg daily; two weeks later, the dose was increased to 40mg daily. However, the patient continued developing acral purpuric lesions and had increasing acral pain, therefore, the patient was started on therapy with rituximab at a dose of 375 mg/mm2 weekly, four infusions total. By the fourth infusion, the patient's cryoglobulins were detected for the first time. As the patient's did not change, an additional two infusions regimen was added given monthly. Three months after the patient's last infusion with rituximab, his acral lesions healed roughly and the therapy with prednisone was slowly tapered and stopped.   Eighteen months after the patient's initial presentation, the patient had increasing acral ischemic symptoms and elevated IgM and low C4, which led to plan other four rituximab infusions. Nevertheless, after the second set of infusions, the patient developed palpable purpura on his legs. The patient then had a biopsy and leukocytoclastic vasculitis was found and direct immunofluoresencse microscopy found IgG in the vessel walls. Therefore, the patient was again treated with prednisone 40mg daily which was tapered and stopped over three weeks and the hematologist administered another another four weekly infusions of intravenous rituximab. Subsequently the patient was referred to a different facility and type II cryoglobulin was identified and characterized as IgM k monoclonal cryoglobulinemia with polyclonal IgG cryoglobulinemia. The patient also had a bone marrow biopsy and the results was normal.   Twenty months after the initial presentation, the patient started therapy with oral cyclophosphamide 100mg daily and oral prednisone 10mg daily. The patient's symptoms and clinical findings were controlled with this regimen and three years after his initial presentation, the patient's doses had been decreasing: cyclophosphamide 50mg every other day and prednisone 5mg daily, however, the patients low level of C4 persisted.   The authors stated that the mechanisms of vasculitis and cryoglobulinemia induced by pneumococcal vaccine, polyvalent (23-valent)(manufacturer unknown) or with influenza virus vaccine (unspecified) remained unknown. It was not possible to ascertain which vaccine was responsible for this patient's disease.