Objective:

To describe and analyze small fiber neuropathy (SFN) cases with autoantibodies and punch biopsy specimens with inflammation. 

Background:

SFN is increasingly prevalent, and a high proportion of previously idiopathic cases may have TS-HDS, FGFR-3, or Plexin-D1 autoantibodies (seropositive). Previously immunoreactivity of TS-HDS, FGFR-3, and Plexin D1 has been demonstrated on human nerves or animal sensory neurons. No study has shown inflammation on seropositive skin biopsy specimens.

Design/Methods:

A retrospective analysis of all punch biopsies in seropositive cases revealed 83 patients, of which 5 (6%) had superficial lymphocytic perivascular inflammation.  Demographics and clinical features were analyzed.

Results:

Of these 5, 3 were female (60%) and 2 were male (40%). The average age of onset was 39.4 (16-57). Five patients (100%) had pain, 4 had burning (80%), 4 had numbness (80%), 5 had paresthesias (100%), and 2 had dysautonomia (40%). One patient (20%) had facial/head involvement, 2 (40%) had truncal, 4 (80%) had arm, and 5 (100%) had leg involvement. Two patients had TS-HDS and 1 patient had TS-HDS and Plexin D1 antibodies, 1 had FGFR-3 and 1 had FGFR-3 and Plexin D1 antibodies. The average Utah Early Neuropathy Scale score was 3, pain score 4.8/10, SFN-RODS 47.6, SFN-SIQ 12.6 and SFN-SL 31.4. Three patients (60%) had non-length dependent (NLD) inflammation present, whereas 1 (43%) different patient had NLD-epidermal nerve fiber density.2 patients (40%) had CD3-immunostain showing a predominance of T-cells in the infiltrate. No patients received immunomodulatory treatment yet.

Conclusions:

Inflammation was seen in a small portion of seropositive biopsies, but suggests an immune mechanism at the ganglion level, and provides further proof of autoimmunity in seropositive-SFN. These patients often have moderate to severe SFN symptoms and pain, exam findings, and disability. Further studies may be indicated to assess whether biopsy-inflammation is a marker for immunomodulatory treatment responsiveness.