How do you manage IgM related peripheral neuropathy?

First things first, let's make sure it's IgM related. In patients with precursor disease (MGUS or smoldering) and neuropathy, I check B12, HbA1c, TSH, free T4, hepatitis B surface Ag, hepatitis B total core Ab, hepatitis C antibody, and cryoglobulins. In patients with specific risk factors, I check for HIV. For patients with substance use disorder, post-gastrectomy, or unintended weight loss, I check thiamine, folate, copper, and phosphate. Patients with progressive or persistent neuropathy should consider EMG/NCV, TTR genetic testing, and potentially skin biopsy to assess for small fiber neuropathy. Clearly in patients with IgM MGUS, should have anti-MAG and anti-ganglioside antibodies.

How to treat? It's appearing to treat the cell of or...

I see a number of these cases and I can tell you what I have learned through experience.

When the underlying process is LPL/waldenstrom’s, single agent Rituximab for 4 weekly doses can be highly effective. I give it six months to see improvement. I track IgM and not the MAG antibodies for improvement in blood work. But it’s really all about symptoms. If there was a partial improvement after 6 months, I usually do one more cycle of Rituximab.
You would think that it is better to start treatment once a patient’s neuropathy worsens, but the demyelination that occurs is rarely reversible in advanced neuropathies. So treating patients early when their symptoms are more subtle may be a better move. The recent approval of zanubrutinib makes for an...