Where should a patient with a serum protein electrophoresis (SPE) pattern showing a polyclonal increase in gamma globulins be referred?

Referral for Polyclonal Increase in Gamma Globulins on SPE

A patient with a polyclonal increase in gamma globulins on serum protein electrophoresis should be evaluated for chronic infections (particularly hepatitis B and C) and autoimmune diseases rather than referred to hematology, as this pattern reflects chronic inflammation or infection, not a malignant plasma cell disorder. 1

Primary Evaluation Strategy

The workup should focus on identifying the underlying inflammatory or infectious cause, as treatment targets the root condition rather than the hypergammaglobulinemia itself. 1

Initial Screening for Infectious Causes

• Screen for hepatitis B and C serologies first, as these are the most important infectious causes and represent readily treatable conditions, particularly when evaluating immune complex-mediated patterns. 1
• Evaluate for other chronic infections based on clinical context, including bacterial, fungal, parasitic, protozoal, mycoplasma, and mycobacterial infections. 1
• In patients with renal involvement showing immune complex-mediated patterns, a polyclonal immunoglobulin and complement pattern most often indicates infectious or autoimmune disease. 2

Autoimmune Disease Evaluation

• Perform serologic testing for autoimmune disorders including antinuclear antibody (ANA) or more specific autoantibodies based on clinical presentation. 1
• Key autoimmune causes to consider include systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and mixed cryoglobulinemia. 1
• Chronic inflammatory conditions such as bronchiectasis frequently show polyclonal rises in serum IgG and IgA. 3, 1

Critical Distinction from Monoclonal Processes

You must differentiate polyclonal increases from monoclonal gammopathies, which appear as discrete peaks on SPEP and may indicate multiple myeloma, Waldenström's macroglobulinemia, or MGUS. 3, 1

When to Consider Hematology Referral

• If clinical suspicion for a monoclonal process remains high despite apparent polyclonal increase, perform more sensitive testing such as serum immunofixation electrophoresis (SIFE) or serum free light chain assay. 3
• In adults ≥50 years with complement-mediated glomerular disease, evaluate for monoclonal proteins even if the initial pattern appears polyclonal. 1
• In patients with polyneuropathy of unknown etiology, approximately 10% have monoclonal gammopathies that may initially appear as polyclonal increases, requiring immunofixation electrophoresis. 1, 4

Specialty Referral Algorithm

Nephrology Referral

• Refer to nephrology if there is evidence of immune complex-mediated glomerulonephritis with polyclonal immunoglobulin and complement deposition. 2

Infectious Disease Referral

• Consider infectious disease consultation for complex or chronic infections identified during workup. 1

Rheumatology Referral

• Refer to rheumatology when autoimmune serologies are positive or clinical features suggest systemic autoimmune disease. 1

Pulmonology Referral

• Consider pulmonology for chronic inflammatory lung conditions such as bronchiectasis with polyclonal rises in IgG and IgA. 3

Common Pitfalls to Avoid

• Do not reflexively refer to hematology for polyclonal patterns, as these represent reactive processes rather than clonal disorders. 3, 1
• Rare cases may show malignancy as a source of chronic antigenemia, though this is uncommon. 1
• In renal disease with polyclonal B-cell activation, there may be increased levels of both κ and λ light chains but with a normal ratio, unlike monoclonal disorders. 3