Intraepidermal nerve fibre density in patients with small fibrepolyneuropathy with and without simultaneous large fibreaffection

Background and Aims: The diagnosis of small fibre neuropathy (SFN) is currently based on the clinical picture, quantitative sensory testing (QST), and autonomic function assessment. Decreased density of and structural abnormities in intraepidermal innervation seem to be morphological correlates of small-fibre dysfunction, and recent studies emphasize the importance of skin biopsy examination in painful sensory neuropathies. The aim of this study was to compare intraepidermal nerve fibre (IENF) density in skin punch biopsy samples in a group of SFN patients with healthy volunteers, and to assess the influence of simultaneous large nerve-fibre involvement on IENF counts. Methods: PGP 9.5-immunoreactive intraepidermal nerve fibre (IENF) density was measured in 76 patients with painful sensory neuropathy and in 25 healthy controls. All patients suffered from subacete or chronic distal sensory symptoms with burning feet and had abnormal thermal thresholds in QST. 42 of the patients also had abnormities in nerve conduction studies and EMG examination as a sign of large fibre affection. Results: The mean IENF count per mm of epidermis was 11.5+-2.9 in healthy volunteers, 5.7+-4.1 in the patients with, and 6.2+-3.5 in the patients without large nerve fiber affection, respectively. Using a lower limit of normal derived from our group of healthy volunteers of 6.7 fibers per mm, an abnormal IENF count was present in 65% of patients with pure small fiber neuropathy and in 69% of patients with involvement of both small and large nerve fibres. Conclusions: IENF counts seem to particularly reflect small nerve fiber status and were not significantly influenced by large fiber affection. Our findings therefore confirm the hypothesis that cutaneous nerves originate predominatly from small nerve fibers and corroborate the usefulness of IENF examination in small fiber neuropathy patients.