Serum protein electrophoresis (SPEP) is sometimes ordered when investigating paresthesia—tingling, numbness, or burning sensations—because it can help identify underlying conditions that may affect the nerves. Paresthesia can stem from various causes, including systemic diseases, vitamin deficiencies, or neurological issues, and SPEP is particularly useful for detecting abnormalities in blood proteins that might point to specific disorders. Here’s why it’s relevant:
Multiple Myeloma Screening: SPEP is often used to check for monoclonal gammopathy, a hallmark of multiple myeloma or related plasma cell disorders. These conditions can cause peripheral neuropathy, leading to paresthesia. Myeloma may damage nerves through paraproteins (abnormal antibodies) or amyloid deposits, which SPEP can indirectly suggest by detecting abnormal protein spikes.

Monoclonal Gammopathy of Undetermined Significance (MGUS): MGUS, a benign condition with abnormal proteins, can also cause neuropathy and paresthesia in some cases. SPEP helps identify these proteins, guiding further evaluation.

Chronic Inflammatory Conditions: Diseases like chronic inflammatory demyelinating polyneuropathy (CIDP) or other immune-mediated neuropathies can present with paresthesia. SPEP may reveal abnormal protein patterns, such as elevated gamma globulins, suggesting an inflammatory or autoimmune process.

Vitamin B12 Deficiency: While SPEP itself doesn’t diagnose B12 deficiency, it’s sometimes part of a broader workup for paresthesia caused by neuropathy. If macrocytic anemia (linked to B12 deficiency) is suspected, SPEP might be used to rule out other causes of abnormal proteins or to assess for related conditions.

Other Systemic Diseases: SPEP can detect protein abnormalities associated with systemic conditions like liver disease, kidney disease, or connective tissue disorders, which might indirectly contribute to neuropathic symptoms.

Why It’s Ordered
Paresthesia has a wide differential diagnosis, and SPEP is typically not a first-line test. It’s ordered when clinical suspicion arises for conditions like multiple myeloma or amyloidosis—especially if paresthesia is accompanied by symptoms like fatigue, bone pain, weight loss, or abnormal bloodwork (e.g., elevated calcium, anemia, or kidney dysfunction). It’s also considered if nerve conduction studies or initial tests (like B12 levels, glucose, or thyroid function) are inconclusive.
Limitations
SPEP alone won’t directly explain paresthesia in most cases. It’s a screening tool, and abnormal results (e.g., a monoclonal spike) often require follow-up tests like immunofixation, bone marrow biopsy, or imaging. Common causes of paresthesia, like diabetes, carpal tunnel syndrome, or medication side effects, aren’t diagnosed with SPEP.