Introduction

Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification.

Areas covered

This review highlights key advances, recent clinical trial updates and ongoing studies on the management of persistent and refractory CryoVas. Therapeutic strategies and treatment agents to manage the disease are described. A literature review was performed by searching for available research studies published before January 2020 on the Medline (PubMed) database.

Expert opinion

Antiviral therapy with direct antiviral agents is the mainstay of treatment for patients with HCV-associated CryoVas. B-cell depleting strategies, mainly with rituximab, is the main therapeutic option in severe and refractory cases of infectious and noninfectious CryoVas. Ongoing trials are currently exploring other targeted biological treatments in this setting.

中文翻译：

---

预防持续性或复发性混合性冷球蛋白血症的策略

介绍

混合性冷球蛋白血症（MC）是免疫复合物，可沉积在中小动脉中，并引起称为冷珠蛋白性血管炎（CryoVas）的全身性血管炎。CryoVas最常见的临床表现包括紫癜，关节痛和/或关节炎，皮肤溃疡，周围神经病变，肾炎，并可能发展为威胁生命的疾病。丙型肝炎病毒（HCV）感染是MC患者中最常见的疾病，其次是结缔组织疾病和B细胞非霍奇金淋巴瘤。在HCV相关病例中，CryoVas治疗的主要手段是无干扰素的抗病毒治疗。但是，显示根除HCV的大部分患者会发展为持续性CryoVas，需要加强治疗。

覆盖区域

这篇综述重点介绍了持续性和难治性CryoVas的关键进展，近期临床试验更新以及正在进行的研究。描述了治疗疾病的治疗策略和治疗剂。通过检索2020年1月之前在Medline（PubMed）数据库上发表的可用研究进行文献综述。

专家意见

直接抗病毒药物的抗病毒治疗是HCV相关性CryoVas患者的主要治疗手段。在感染性和非感染性CryoVas的严重和难治性病例中，主要使用利妥昔单抗的B细胞耗竭策略是主要的治疗选择。目前正在进行的试验正在探索这种情况下的其他靶向生物治疗。