Rare Complete Restoration of Intraepidermal Nerve Fibre Density by Immunoglobulins in Post-COVID Vaccination Syndrome-Associated Small Fibre Neuropathy: A Case Report and Literature Review.

This report describes the rare complete restoration of reduced intraepidermal nerve fibre density (IENFD) following the administration of intravenous immunoglobulins (IVIG) in a patient with post-acute COVID-19 vaccination syndrome (PACVS) that manifested, among other symptoms, as small-fibre neuropathy (SFN). The patient was a 53-year-old woman who developed SFN in June 2021 following her second BNT162b2 vaccination. Clinically, the SFN presented with symptoms including sensory disturbances, arterial hypotension, and orthostatic tachycardia. After eight cycles of IVIG therapy from June 2024 to February 2025, three years after the onset of PACVS, a significant improvement in the clinical SFN symptoms was observed. Additionally, the IENFD improved from 6 at the ankle and thigh before IVIG therapy to 9 at the ankle and 8 at the thigh after therapy. The skin biopsy in 2026 was unremarkable. The spike protein was detectable in peripheral blood mononuclear cells, as were vaccine plasmid DNA remnants in the skin biopsies before and after IVIG therapy. S100 protein staining was weakly positive before and after IVIG administration. We report the case of a 53-year-old female patient who presented with sensory and autonomic disturbances; following a skin biopsy, she was diagnosed with PACVS-associated SFN. Treatment with IVIG over several months led to an improvement in symptoms and a complete restoration of IENFD. This case highlights the importance of diagnosing PACVS-associated SFN and the beneficial effect of IVIG, which not only improves the clinical manifestations of SFN but also normalises IENFD.