What are cryoglobulins?

From the Guidelines

The management of mixed cryoglobulinemia syndrome (MCS) in hepatitis C virus-infected patients should prioritize antiviral therapy, such as IFN-free regimens, and immunosuppressive therapy, including rituximab, to eradicate HCV, limit B lymphocyte proliferation, and contain vasculitis, as supported by recent studies 1. The treatment of MCS is still largely empirical, but the goal is to prevent irreversible organ damage, reduce pain, and improve the patient's quality of life.

• The use of rituximab, an anti-CD20 monoclonal antibody, has shown encouraging results in improving or curing various clinical manifestations of MCS, including fatigue, skin manifestations, arthralgias, and glomerulonephritis 1.
• Antiviral therapy, such as IFN-free regimens, has been associated with improvement of the clinical manifestations of mixed cryoglobulinemia 1.
• Plasmapheresis may be used in severe cases to rapidly remove cryoglobulins from circulation.
• Patients should avoid cold exposure to prevent symptom flares, as temperature changes trigger protein precipitation and subsequent inflammation. The classification of cryoglobulins into three types (Type I, II, and III) is essential for understanding the underlying cause of the disease and guiding treatment decisions.
• Type II mixed cryoglobulins are often linked to hepatitis C, and treatment should focus on eradicating the virus and managing the immune complex-mediated vasculitis.
• The use of immunosuppressants, such as cyclophosphamide or corticosteroids, may be necessary in some cases, but rituximab has shown a steroid-sparing effect in patients with MCS 1. Overall, the management of MCS requires a multidisciplinary approach, and treatment should be tailored to the individual patient's needs, taking into account the underlying cause of the disease, the severity of symptoms, and the presence of any comorbidities.

From the Research

Definition and Classification of Cryoglobulins

• Cryoglobulins are immunoglobulins that precipitate at variable temperatures < 37 degrees C [98.6 degrees F] in serum 2.
• Cryoglobulinemia is classified into three types (I, II, and III) based on immunoglobulin composition 3.
• Type I involves a single type of monoclonal immunoglobulin, while type II and III involve a mixture of polyclonal and monoclonal immunoglobulins 2.

Clinical Manifestations and Diagnosis

• Cryoglobulinemia leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, neuropathy, and glomerulonephritis 3.
• The diagnosis of cryoglobulinemic syndrome is predominantly based on the laboratory demonstration of serum cryoglobulins 3.
• Detection of cryoglobulins in the laboratory can be hampered by several pitfalls, including pre-analytical stage and quantification issues 4.

Treatment Options

• Treatment options are primarily directed by identification of underlying diseases, such as infections or systemic autoimmune diseases 4.
• Conventional immunosuppression, antiviral treatment, and biologic therapy are the three main broad treatment strategies in cryoglobulinemia 2.
• Plasma exchange has been advocated as an effective treatment in reducing morbidities associated with cryoglobulinemia, particularly in conjunction with immunosuppressive therapy 5, 6.
• Idiopathic cryoglobulinaemia is treated with corticosteroids and immunosuppression, or B cell depleting anti-CD20 biologicals 4.

Underlying Diseases and Associations

• Predisposing conditions for cryoglobulinemia include lymphoproliferative disease, collagen disease, and hepatitis C virus (HCV) infection 3.
• Hepatitis C virus (HCV) is a well-known factor in the aetiology of cryoglobulinaemia, but substantial geographical differences exist in the association between cryoglobulins and HCV 4.