Autonomic small-fiber pathology in patients with fibromyalgia

In this clinical and skin biopsy study we aimed to investigate whether fibromyalgia-associated small-fiber pathology, consisting of an intraepidermal nerve fiber loss, implies a damage of dermal autonomic nerve fibers and how this damage is associated with autonomic symptoms that patients with fibromyalgia syndrome experience. Using skin biopsy, we investigated intraepidermal nerve fiber density, piloerector muscle, and sweat gland nerve fiber density in 138 participants - i.e. 58 patients with fibromyalgia syndrome, 48 healthy subjects, and 32 patients with small-fiber neuropathy. In patients with fibromyalgia-associated small-fiber pathology we also investigated how the different skin biopsy variables correlated with autonomic symptoms, as assessed with the Composite Autonomic Symptom Score (COMPASS-31) questionnaire. We found that in patients with fibromyalgia-associated small-fiber pathology, the piloerector muscle and sweat gland nerve fiber density was lower than that in healthy subjects. However, the autonomic small-fiber damage had no correlation with autonomic symptoms severity. In patients with small-fiber pathology the intraepidermal, piloerector muscle, and sweat gland nerve fiber density was higher than that in patients with small-fiber neuropathy. Our clinical and skin biopsy study shows that patients with fibromyalgia have a reduction of dermal autonomic small fibers paralleling the intraepidermal nerve fiber loss, thus indicating that small-fiber pathology also implies autonomic small nerve fiber damage. However, the autonomic small-fiber damage we found had no correlation with the severity of autonomic symptoms, and thus its clinical impact is still undetermined. PERSPECTIVE: In patients with fibromyalgia, small-fiber pathology also affects autonomic fibers. These novel data provide additional insights on the pathophysiology of fibromyalgia syndrome, highlighting the complex role of small-fiber damage in the clinical picture of fibromyalgia.