Small-fibre neuropathy in coeliac disease: a cross-sectional study

Coeliac disease (CD) is associated with neurological manifestations, including peripheral neuropathy. While sensorimotor neuropathy has been described, objective evidence for small-fibre neuropathy (SFN) in CD remains limited. We aimed to assess large- and small-fibre involvement in patients with CD with and without neuropathic symptoms using contemporary diagnostic standards.

In this cross-sectional study, 36 adults with biopsy-proven CD were recruited nationwide and stratified by the Neuropathy Symptom Score into symptomatic (pwCD(NS+), NSS ≥ 3) and asymptomatic (pwCD(NS-), NSS < 3) groups. All participants underwent neurological examination, sural nerve conduction studies (NCS), quantitative sensory testing (QST), distal leg skin biopsy for intraepidermal nerve fibre density (IENFD), and autonomic testing.

pwCD(NS+) predominantly reported distal symmetric sensory complaints with neuropathic pain characteristics. NCS were normal in both groups, arguing against relevant sensorimotor neuropathy. Both groups showed a loss-of-function QST profile with impaired thermal detection. IENFD was lower in pwCD(NS+) than in pwCD(NS-) and correlated with symptom severity. Autonomic testing was largely unremarkable. 50% of pwCD(NS+) fulfilled the diagnostic criteria for SFN, while all remaining patients showed abnormalities in at least one small fibre-related domain (clinical examination, IENFD or QST). In pwCD(NS-), isolated abnormalities in QST or IENFD were frequently observed despite the absence of neuropathic symptoms.

In CD, neuropathic symptoms are associated with small-fibre pathology rather than sensorimotor neuropathy. SFN should be considered in the diagnostic work-up of neuropathic complaints in CD, and symptom-oriented treatment is warranted.