Ostojic Predrag, Jeremic Ivan R
Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia.
J Inflamm Res. 2017 May 8;10:49-54. doi: 10.2147/JIR.S114067. eCollection 2017.
Cryoglobulinemia is thought to be a rare condition. It may be an isolated disorder or secondary to a particular disease. According to immunoglobulin composition, cryoglobulinemia is classified into three types. In mixed cryoglobulinemia (types II and III), vascular deposition of cryoglobulin-containing immune complexes and complement may induce a clinical syndrome, characterized by systemic vasculitis and inflammation - cryoglobulinemic vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy, Raynaud's phenomenon, sicca syndrome, membranoproliferative glomerulonephritis, and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia, prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by polymerase chain reaction (PCR), is reported to be up to 90%, indicating a significant role of HCV in the development of this condition. The goals of therapy for mixed cryoglobulinemia include immunoglobulin level reduction and antigen elimination. CryoVas not associated with HCV infection should be treated according to treatment recommendations for small-vessel vasculitides. CryoVas associated with chronic HCV infection should be treated with antivirals along with immunosuppressive drugs, with or without plasmapheresis, depending on disease severity and organ involvement. Patients who do not respond to first-line therapy may achieve remission when treatment with rituximab is started as second-line therapy. In HCV-related CryoVas, antiviral therapy should be given along with rituximab in order to achieve complete or partial remission. Moreover, rituximab has proven to be a glucocorticoid-sparing medication. Other potential therapies for refractory CryoVas include mycophenolate mofetil and belimumab, while tumor necrosis factor (TNF) inhibitors are not effective.
冷球蛋白血症被认为是一种罕见病症。它可能是一种孤立性疾病，也可能继发于某一特定疾病。根据免疫球蛋白组成，冷球蛋白血症可分为三型。在混合型冷球蛋白血症（II型和III型）中，含冷球蛋白的免疫复合物和补体的血管沉积可诱发一种临床综合征，其特征为系统性血管炎和炎症——冷球蛋白血症性血管炎（CryoVas）。CryoVas最常见的临床表现为皮肤病变（直立性紫癜和溃疡）、乏力、周围神经病变、雷诺现象、干燥综合征、膜增生性肾小球肾炎以及关节痛，很少出现关节炎。据报道，在混合型冷球蛋白血症患者中，通过聚合酶链反应（PCR）检测到的抗丙型肝炎病毒（HCV）抗体和/或HCV RNA的患病率高达90%，这表明HCV在该病症的发生发展中起重要作用。混合型冷球蛋白血症的治疗目标包括降低免疫球蛋白水平和清除抗原。与HCV感染无关的CryoVas应根据小血管血管炎的治疗建议进行治疗。与慢性HCV感染相关的CryoVas应根据疾病严重程度和器官受累情况，使用抗病毒药物联合免疫抑制药物进行治疗，可联合或不联合血浆置换。对一线治疗无反应的患者，开始使用利妥昔单抗作为二线治疗时可能会实现缓解。在HCV相关的CryoVas中，应将抗病毒治疗与利妥昔单抗联合使用，以实现完全或部分缓解。此外，利妥昔单抗已被证明是一种可减少糖皮质激素用量的药物。难治性CryoVas的其他潜在治疗方法包括霉酚酸酯和贝利木单抗，而肿瘤坏死因子（TNF）抑制剂无效。
