Peripheral Neuropathy in IgA Gammopathy: Prevalence And Red Flags

Key Takeaways

• Neuropathy was documented in 13.5% of the cohort, and most affected patients were classified as having neuropathy unrelated to IgA.
• The rare IgA-related subgroup was observed mainly in AL amyloidosis and POEMS syndrome rather than across the broader neuropathy spectrum.
• Lambda light chains, pain, autonomic dysfunction, and fatigue or weight loss were observed in IgA-related cases within this retrospective single-center study.

In a retrospective cohort of IgA gammopathy and peripheral neuropathy, neuropathy was documented in 79 of 585 patients newly diagnosed with IgA gammopathy. After specialist review, most cases were not attributed directly to the gammopathy, leaving IgA-related neuropathy as an uncommon finding within a diagnostically mixed group. Across the newly diagnosed cohort, direct IgA-related neuropathy was uncommon, and the overall neuropathy burden was etiologically heterogeneous.

This retrospective single-center French study included all patients with newly diagnosed IgA gammopathy identified by serum immunofixation from January 2016 through December 2020. Among 647 identified patients, 62 were excluded because of missing data, leaving 585 patients for analysis. Neuropathy ascertainment came from electronic medical records, and two neurologists or peripheral nerve specialists reviewed the likely etiologic classification. The median age at IgA onset was 65 years, and mean follow-up from diagnosis was 4 years, providing the basis for prevalence and classification estimates.

Etiologic review divided neuropathy cases into 10 IgA-related cases, 64 IgA-unrelated cases with an identified alternative cause, and 5 neuropathies of uncertain relationship with IgA. That translated to 1.7% of the entire cohort, 12.7% of neuropathy cases, 81% classified as unrelated, and 6.3% considered uncertain. Chemotherapy-induced neuropathy accounted for 34 cases and diabetic neuropathy for 15, while alcoholism, vitamin deficiency, chronic kidney disease, genetic disease, and vasculitis were also reported. Most of the observed neuropathy burden therefore reflected alternative etiologies rather than direct IgA-related disease.

This IgA-related subgroup comprised 8 AL amyloidosis and 2 POEMS syndrome cases, and all carried lambda light chains. Within these AL amyloidosis and POEMS syndrome cases, neuropathic pain and autonomic dysfunction were each reported in 70%, while fatigue or weight loss appeared in 80%. The median monoclonal peak in IgA-related cases was 8.2 g/L, and lambda light chains appeared in 50.6% of the overall cohort. Confirmation of AL amyloidosis often required more than one tissue sample, and these features clustered in the rare IgA-related cases identified here.

Five patients were classified as NURIA, including four mild sensory-predominant length-dependent axonal neuropathies and one severe progressive motor-predominant axonal neuropathy. Limitations included the retrospective design, dependence on medical records, missing-data exclusions, possible undercapture of pauci-symptomatic neuropathy in a hospital-based cohort, and no direct comparison with other gammopathy types. The small number and limited characterization of uncertain cases also constrained interpretation of that subgroup.

Overall, neuropathy in IgA gammopathy showed low prevalence and a broad etiologic spectrum, with AL amyloidosis and POEMS syndrome accounting for the reported IgA-related subset.