Immunofixation Electrophoresis in Bilateral Foot Burning/Numbness

Rationale for IFE Testing

The American Academy of Physical Medicine and Rehabilitation recommends immunofixation electrophoresis (IFE) for patients with bilateral foot burning/numbness as it can detect monoclonal gammopathies that may cause peripheral neuropathy, which are found in approximately 10% of patients with polyneuropathy of unknown etiology 1
IFE is more sensitive than serum protein electrophoresis (SPEP), especially for detecting small or non-malignant monoclonal gammopathies 1
In patients with polyneuropathy of otherwise unknown etiology, approximately 10% have monoclonal gammopathy, which is a significant increase over the general population 1

Waldenström's macroglobulinemia, which often presents with neuropathy, can be detected by IFE 2
AL amyloidosis, which can cause peripheral neuropathy with autonomic features, can be detected by IFE 3
Multiple myeloma with neuropathic manifestations can be detected by IFE 4, 5

IFE has superior sensitivity compared to SPEP, with studies showing IFE can detect monoclonal proteins in approximately 30% of cases that were missed by SPEP 1
IFE can detect IgM antibodies associated with myelin-associated globulin (anti-MAG), which are found in approximately 50% of patients with demyelinating symmetric sensory peripheral neuropathy 2

Initial laboratory evaluation should include serum protein immunofixation electrophoresis (IFE) to detect monoclonal gammopathies 1
If IFE detects a monoclonal protein, collaborate with a hematologist to determine whether findings represent MGUS, AL amyloidosis, or multiple myeloma 3

Relying solely on SPEP can miss approximately 30% of monoclonal gammopathies that would be detected by IFE 1
It's essential to differentiate polyclonal increases in immunoglobulins from monoclonal gammopathies when evaluating polyneuropathy 6