Key Takeaways

✅ Polyclonal gammopathy (PG) is a type of hypergammaglobulinemia that results from an increased production of several different immunoglobulins by plasma cells.

✅ PG is most commonly associated with liver disease, acute or chronic inflammation, autoimmune disorders and certain malignancies.

✅ PG is generally considered a benign condition that does not progress to overt malignancy.

✅ PG may provide an important clue for less common difficult-to-diagnose conditions, such as eosinophilic granulomatosis with polyangiitis, IgG4-related disease, and Rosai–Dorfman disease.

✅ PG is part of the diagnostic criteria for rare diseases such as Idiopathic multicentric Castleman disease and Autoimmune lymphoproliferative syndrome (APLS).

✅ PG is diagnosed by serum protein electrophoresis and immunofixation electrophoresis (SPEP/IFE) showing a polyclonal increase in immunoglobulins (having 1 or more heavy-chain classes and both kappa and lambda light-chain types).

✅ Work up should focus on eight causes (“buckets”) of polyclonal hypergammaglobulinemia:

• Liver disease
• Autoimmune disease and vasculitis
• Infection and inflammation
• IgG4-related disease
• Hematological disorders
• Non-hematological malignancy
• Immunodeficiency
• Iatrogenic

✅ Treatment includes treating the underlying disease/cause and plasma exchange in VERY rare cases in which polyclonal hyperglobulinemia results in hyperviscosity.