From the Guidelines
Polyclonal gammopathy is a condition characterized by an elevation of multiple immunoglobulin classes produced by different B-cell populations, and its management focuses on treating the underlying cause, which can include chronic infections, inflammatory disorders, liver disease, and certain cancers. This condition presents as an elevation of multiple immunoglobulin classes (IgG, IgA, and/or IgM) rather than a single clone, and clinically, patients may be asymptomatic or present with symptoms related to the underlying cause, such as fatigue, fever, weight loss, or specific organ dysfunction 1. Laboratory findings typically show elevated total protein, increased gamma fraction on serum protein electrophoresis with a broad-based peak, and normal calcium levels.
Key Characteristics and Management
- Polyclonal gammopathy is often associated with underlying infections, such as HBV or HCV, bacterial or parasitic disease, or autoimmune diseases, and thus screening for these conditions is crucial 1.
- Treatment should focus on the underlying cause, and in rare cases, malignancy should be considered as a source of chronic antigenemia 1.
- Serum and urine immunoelectrophoresis and immunofixation, as well as a serum free light chain analysis, are recommended for all adult patients with complement-dominant MPGN to rule out a paraprotein 1.
- Regular monitoring with serum protein electrophoresis is recommended to ensure resolution and to detect any evolution to monoclonal gammopathy, which would require different management.
- Supportive care may be needed to address symptoms related to the underlying condition, and the condition itself typically resolves when the underlying condition improves.
Underlying Causes and Treatment Approach
- Common causes of polyclonal gammopathy include chronic infections, inflammatory disorders, liver disease, and certain cancers.
- Treatment involves addressing the primary disease with appropriate antimicrobials for infections, immunosuppressants for autoimmune conditions, or specific therapy for malignancies.
- The focus of management is on treating the underlying condition rather than the gammopathy itself, as polyclonal gammopathy does not typically require specific treatment.
From the Research
Definition and Causes of Polyclonal Gammopathy
- Polyclonal gammopathy refers to an increase in the levels of immunoglobulins (antibodies) in the blood, which can be caused by various conditions such as liver disease, immune dysregulation, or inflammation 2.
- It can also be associated with rare diseases like histiocyte disorders, autoimmune lymphoproliferative syndrome, Castleman disease, and IgG4-related disease 2.
- The causes of polyclonal hypergammaglobulinaemia can be divided into eight categories: liver disease, autoimmune disease and vasculitis, infection and inflammation, non-haematological malignancy, haematological disorders, IgG4-related disease, immunodeficiency syndromes, and iatrogenic (from immunoglobulin therapy) 2.
Clinical Presentation and Symptoms
- The clinical presentation of polyclonal gammopathy can vary depending on the underlying cause, but it is often characterized by chronic inflammation and elevated levels of immunoglobulins in the blood 2, 3.
- Symptoms may include fatigue, weight loss, and recurrent infections, as well as specific symptoms related to the underlying condition, such as liver disease or autoimmune disorders 2, 4.
- In some cases, polyclonal gammopathy can lead to hyperviscosity, which requires plasmapheresis to remove excess immunoglobulins from the blood 2.
Diagnosis and Management
- Diagnosis of polyclonal gammopathy involves measuring serum concentrations of C-reactive protein and IgG subclasses, as well as assessing the underlying cause of the condition 2.
- Management of polyclonal gammopathy typically involves treating the underlying condition, and in some cases, may require immunoglobulin replacement therapy to reduce the risk of infections 5.
- In patients with recurrent infections, immunoglobulin replacement has been shown to reduce the rate of non-severe infections 5.