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IgM paraprotein-associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B-cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein-associated PN identified five patients with small pathological MYD88 L265P and CD20-positive B-cell clones in their bone marrow using multi-parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi-parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein-associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B-cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall.

The bottom line A previously well 25 year old man presents to his general practitioner with a six month history of crampy abdominal pain, bloating, and diarrhoea, with passage of loose stools up to six times a day. There is urgency but no incontinence. On clinical examination he has mild lower abdominal tenderness, but digital rectal examination is normal. Chronic diarrhoea can be defined pragmatically as the passage of loose stools more than three times a day for at least four weeks.1 A patient’s own perception of diarrhoea may be markedly different, and it is essential to clarify—for example, faecal incontinence is commonly misconstrued as diarrhoea.1 Irritable bowel syndrome (IBS), a functional disorder, is the most prevalent cause of chronic diarrhoea.2 Other important causes include inflammation (inflammatory bowel disease (IBD), microscopic colitis, and more rarely infection), bile acid diarrhoea, malabsorption (coeliac disease, lactose intolerance, and pancreatic insufficiency), drugs, food additives, and endocrine conditions (thyrotoxicosis and diabetes). Clinicians should always be mindful of an underlying cancer, particularly in patients over 45 years, and …