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.

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