Influenza virus vaccine
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Mixed cryoglobulinaemia: case report A 76-year-old man developed mixed cryoglobulinaemia following administration of influenza virus vaccine. The man had received influenza virus vaccine [trivalent influenza vaccine; dosage and route not stated] along with concomitant pneumococcal vaccination. After 5 days, he experienced flu-like symptoms and cyanosis of the fingers and toes, following which he presented. He had non-palpable, purpuric lesions on his fingers and toes along with acral pain. He progressively had deteriorating digital ischaemia and purpura along with livedo reticularis of both the plantar surfaces. Within 4 weeks of vaccine administration he experienced anorexia, myalgia, night sweats, fatigue and arthralgia. Laboratory investigations revealed increased rheumatoid factor, along with decreased values of total haemolytic complement level [CH50], C3 level and C4 level, and increased Westergren ESR, CRP, anti-phosphatidylserine IgG and anti-phosphatidylserine IgM values. Initial testing for cryoglobulins revealed negative result. After two weeks, his rheumatoid factor increased further. The man was treated with prednisone, dose of which was increased after 2 weeks. Despite this treatment he continued to develop new acral purpuric lesions and had incraesed acral pain. Therefore, 6 weeks into prednisone, rituximab therapy was administered. However, due to limited clinical change, an additional 2 infusions of rituximab were administered monthly. At the end of his fourth infusion of rituximab, cryoglobulins were observed for the first time. Three months after his last rituximab infusion, his acral lesions had healed. His cryoglobulin level was detectable on continuous monitoring. On month 18 following the initial presentation, he had increased acral ischaemic symptoms, an increased IgM level and decreased C4 level, for which he was scheduled to receive another session of four rituximab infusions. However, prior to the second set of infusions, he developed palpable purpura on his legs. A biopsy revealed leucocytoclastic vasculitis, and direct immunofluorescence microscopy revealed IgG in the vessel walls. He was treated with prednisone, which was tapered and discontinued over 3 weeks. His haematologist administered another 4 weekly infusions of rituximab. Investigations revealed type II cryoglobulin characterised as IgMκ monoclonal cryoglobulinaemia with polyclonal IgG cryoglobulinaemia. Based on these clinical presentation and findings, he was diagnosed with mixed cryoglobulinaemia secondary to influenza virus vaccine. Twenty months following the initial presentation, he began therapy with cyclophosphamide and prednisone. Subsequently, his cryoglobulinaemia had improved. During the latest follow up, though his physical findings and symptoms remained in control, the decreased level of C4 had persisted. Author comment: "[Influenza virus vaccine] induced cryoglobulinemia is the most probable cause of our patient’s symptoms." Eid S, et al. Type II mixed cryoglobulinemia following influenza and pneumococcal
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