SPEP Should Be Ordered for Peripheral Neuropathy Evaluation
Serum protein immunofixation electrophoresis (IFE) should be ordered as part of the initial laboratory workup for peripheral neuropathy evaluation, as it is one of the tests with the highest yield of abnormality in determining the cause of distal symmetric polyneuropathy. 1, 2
Rationale for SPEP/IFE Testing in Peripheral Neuropathy
- Monoclonal gammopathies are more common in patients with polyneuropathy than in the normal population, with approximately 10% of patients with polyneuropathy of unknown etiology having a monoclonal gammopathy 1, 3
- Serum protein immunofixation electrophoresis (IFE) is more sensitive than serum protein electrophoresis (SPEP), especially for detecting small or non-malignant monoclonal gammopathies 1, 4
- Studies show that IFE can detect monoclonal proteins in approximately 17% of cases that were missed by SPEP alone, including 30% of cases with IgM < 5g/L 1
- Failure to screen for monoclonal proteins can lead to missed diagnoses of conditions like AL amyloidosis and POEMS syndrome, which can have significant impacts on morbidity and mortality 5
Conditions Detectable by SPEP/IFE That Can Cause Neuropathy
- IgM monoclonal gammopathies may be associated with autoantibody activity, type I or II cryoglobulinemia, macroglobulinemia, or chronic lymphocytic leukemia 1
- IgG or IgA monoclonal gammopathies may be associated with myeloma, POEMS syndrome, primary amyloidosis, or chronic inflammatory conditions 1
- Waldenström's macroglobulinemia often presents with neuropathy and can be detected by IFE 1, 4
- In patients with peripheral neuropathy and IgM paraprotein, testing for anti-myelin-associated glycoprotein (anti-MAG) antibodies should be considered 2, 3
Recommended Laboratory Workup for Peripheral Neuropathy
- Blood glucose (fasting blood glucose and/or hemoglobin A1c) to screen for diabetes mellitus, the most common cause of peripheral neuropathy 2
- Serum B12 with metabolites (methylmalonic acid with or without homocysteine) to identify vitamin B12 deficiency 1, 2
- Serum protein immunofixation electrophoresis to evaluate for monoclonal gammopathy 1, 2
- Consider glucose tolerance testing in patients with distal symmetric sensory polyneuropathy if routine blood glucose testing is not clearly abnormal 1
- Additional testing based on clinical presentation may include HIV, hepatitis B and C screening 2
Clinical Implications of Positive Findings
- If a monoclonal protein is detected, collaboration with hematology is recommended to determine whether findings represent monoclonal gammopathy of undetermined significance (MGUS), AL amyloidosis, multiple myeloma, or other conditions 3
- Patients with IgM paraprotein-associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti-MAG antibody 3
- Patients with lambda monoclonal protein and a clinical phenotype resembling chronic inflammatory demyelinating polyneuropathy (CIDP) should be evaluated for POEMS syndrome 3
- Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis 3
Common Pitfalls to Avoid
- Relying solely on SPEP without IFE can miss approximately 17% of monoclonal gammopathies 1, 4
- Failing to screen for monoclonal proteins in patients with peripheral neuropathy of unknown etiology 5, 6
- Overlooking the possibility that a monoclonal gammopathy may be directly related to the neuropathy rather than coincidental 3, 7
- Not considering free light chain testing when SPEP/IFE are normal in patients with peripheral neuropathy of unknown etiology 5
In conclusion, SPEP/IFE testing is a crucial component of the evaluation of peripheral neuropathy and should be included in the initial laboratory workup along with blood glucose and vitamin B12 testing to identify potentially treatable causes of neuropathy and prevent missed diagnoses of serious conditions.