Strategies to prevent persistent or relapsed mixed cryoglobulinemia

ABSTRACT

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.

KEYWORDS:

• Cryoglobulinemia
• vasculitis
• therapy
• chronic hepatitis C
• rituximab

Article highlights

• Treatment of cryoglobulinemic vasculitis (CryoVas) may target either the viral trigger hepatitis C virus (HCV) and/or the downstream B-cell lymphoproliferation.

• Aggressive therapy with direct-acting antivirals should be systematically considered for HCV-CryoVas patients.

• Rituximab (RTX) is an effective and safe option for severe CryoVas patients.

• Management of rituximab-refractory CryoVas remains a major challenge.

• B-cell-targeted therapies other than RTX or low-dose interleukin-2 are the most promising strategies for the management of refractory CryoVas cases.

This box summarizes key points contained in the article.

Declaration of interest

Patrice Cacoub has received consulting and lecturing fees from Abbvie, Astra Zeneca, Bristol-Myers Squibb, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Roche, Servier and Vifor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.