Cutaneous nerve biopsy in patients with symptoms of small fiber neuropathy: a retrospective study

We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences.

Nerve conduction studies (NCS), skin biopsy for determination of intraepidermal nerve fiber density (IENFD) and quantitative sensory testing (QST) were performed. Z-scores were calculated from reference materials to adjust for the effects of age and gender/height.

Two hundred and three patients, 148 females and 55 males had normal NCS and were considered to have possible SFN. 45.3 % had reduced IENFD, 43.2 % of the females and 50.9 % of the males. Mean IENFD was 7.3 ± 2.6 fibers/mm in females and 6.1 ± 2.3 in males (p<0.001), but the difference was not significant when adopting Z-scores. Comparison of gender differences between those with normal and abnormal IENFD were not significant when Z-scores were applied. QST was abnormal in 50 % of the patients (48.9 % in females and 52.9 % in males). In the low IENFD group 45 cases out of 90 (50 %) were recorded with abnormal QST. In those with normal IENFD 51 of 102 (50 %) showed abnormal QST.

Less than half of these patients had reduced IENFD, and 50 % had abnormal QST. There were no gender differences. A more strict selection of patients might have increased the sensitivity, but functional changes in unmyelinated nerve fibers are also known to occur with normal IENFD. Approval to collect data was given by the Norwegian data protection authority at University Hospital of North Norway (Project no. 02028).