Sex: M
Vaccine: PPV, UNK
Symptoms: Myalgia, Night sweats, Pain, Peripheral ischaemia, Purpura
Clinical narrative: Type II mixed cryoglobulinemia; cyanosis of the toes and fingers; nonpalpable, purpuric lesions on his toes and fingers/worsening purpura; acral pain; digital ischemia/increasing acral ischemic symptoms; livedo reticularis of both plantar surfaces; anorexia; night sweats; myalgias; fatigue; arthralgias; flu-like symptoms; leukocytoclastic vasculitis; Initial information received on 07-Nov-2019 regarding an unsolicited valid serious case issued from a literature article.    Abstract: Influenza virus vaccineeinduced cryoglobulinemia has been reported in only 1 patient,1 whereas pneumococcal-induced cryoglobulinemia has never been described. Mixed cryoglobulinemia is a systemic inflammatory syndrome that is caused by the development of immunoglobulins that deposit at low temperatures affecting small and medium blood vessels and may manifest as either an inflammatory or noninflammatory vasculopathy.2 Multiple organs including the skin are most commonly affected.2 Mixed cryoglobulinemia has been regularly associated with Hepatitis C viral infection2 and may persist even when the infection has been eradicated. Vasculitides have been associated with vaccination. We report on a patient without prior immunologic disease whose disease occurred shortly after vaccination with influenza and pneumococcal vaccines, and persisted.  This case involves a 76 years old male patient who experienced type ii mixed cryoglobulinemia (cryoglobulinaemia) while he received vaccines PNEUMOCOCCAL VACCINE (PNEUMOCOCCAL VACCINE) and INFLUENZA VACCINE (TRIVALENT).  The patient's past medical history included Vascular graft and Gastrooesophageal reflux disease. The patient's past medical treatment(s), vaccination(s) and family history were not provided. At the time of the event, the patient had ongoing Coronary artery disease and Hypercholesterolaemia.   On an unknown date, the patient received a dose of suspect INFLUENZA VACCINE (TRIVALENT) produced by unknown manufacturer lot number not reported via unknown route in unknown administration site.  On an unknown date, the patient received a dose of suspect PNEUMOCOCCAL VACCINE not produced by Sanofi Pasteur lot number not reported via unknown route in unknown administration site.  On an unknown date, The patient developed a serious type ii mixed cryoglobulinemia (cryoglobulinaemia), flu-like symptoms (influenza like illness) and cyanosis of the toes and fingers (cyanosis) 5 days following the administration of INFLUENZA VACCINE (TRIVALENT) and PNEUMOCOCCAL VACCINE. These events were assessed as medically significant.  On an unknown date, the patient developed a serious leukocytoclastic vasculitis (hypersensitivity vasculitis), purpuric lesions on his toes and fingers/worsening purpura (purpura), acral pain (pain), digital ischemia/increasing acral ischemic symptoms (ischaemia), livedo reticularis of both plantar surfaces (livedo reticularis) Unknown latency following the administration of INFLUENZA VACCINE (TRIVALENT) and PNEUMOCOCCAL VACCINE. These events were assessed as medically significant.  On an unknown date, the patient developed a serious anorexia (decreased appetite), night sweats (night sweats), myalgias (myalgia), fatigue (fatigue), arthralgias (arthralgia)  4 weeks following the administration of INFLUENZA VACCINE (TRIVALENT) and PNEUMOCOCCAL VACCINE. These events were assessed as medically significant.  Relevant laboratory test results included: Blood immunoglobulin G - On an unknown date: 19 [19] Blood immunoglobulin M - On an unknown date: 64 [64]; on an unknown date: elevated [elevated] C-reactive protein - On an unknown date: 5.24 mg/dL [5.24] Complement factor C3 - On an unknown date: 75.50 mg/dL [75.50] Complement factor C4 - On an unknown date: <1.67 mg/dL [<1.67]; on an unknown date: low level mg/dL [low level] Red blood cell sedimentation rate - On an unknown date: 48 mm/h [48] Rheumatoid factor - On an unknown date: 24 iU/mL [24]; on an unknown date: 54 iU/mL [54] Total complement activity test (60 - 185) - On an unknown date: 28 [28]. A bone marrow biopsy finding was normal.  Final diagnosis was flu-like symptoms, leukocytoclastic vasculitis and type ii mixed cryoglobulinemia.   Corrective treamtnet: was initially treated with oral prednisone, 20 mg daily, which was increased 2 weeks later to 40 mg daily. Intravenous rituximab, 375 mg/mm2, was administered weekly for a total of 4 infusions (additional 2 infusions of rituximab were given monthly.). His acral lesions healed roughly 3 months after his last rituximab infusion. Prednisone, 40 mg daily, was continued throughout the first 3 months of his course and then slowly tapered and stopped 4 months after his last infusion of rituximab. Twenty months after his initial presentation, he began therapy with oral cyclophosphamide, 100 mg daily, and oral prednisone, 10 mg daily. 3 years after his presentation, his doses have been decreased to cyclophosphamide, 50 mg every other day, and prednisone, 5 mg daily.  The patient recovered from nonpalpable, purpuric lesions on his toes and fingers/worsening purpura and outcome is reported as Recovering / Resolving from all other events.  Reporter's causality: based on the timing of the vaccination, constellation of symptoms, and positive laboratory results, influenza virus induced cryoglobulinemia is the most probable cause of our patient's symptoms.  There will be no information available on the batch number for this case.; Sender's Comments: A 76 years old male patient experienced cryoglobulinaemia along with associated  and non-associated events after vaccination with INFLUENZA VACCINE (TRIVALENT) and PNEUMOCOCCAL VACCINE. Time to onset is compatible with the role of the vaccines. Past medical history included Vascular graft and Gastrooesophageal reflux disease. At the time of the event, the patient had ongoing Coronary artery disease and Hypercholesterolaemia. However, further information including concomitant medications, previous vaccination and tolerance would be needed to fully assess this case. Based on available information the role of an individual vaccine not be assessed.