Primary Raynaud phenomenon and small-fiber neuropathy: is there a connection? A pilot neurophysiologic study

Abstract

The pathophysiologic factors of primary Raynaud phenomenon (RP) are unknown. Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in primary RP. We aimed to quantitatively assess SFN in participants with primary RP. Consecutive patients with an a priori diagnosis of primary RP presenting to our outpatient rheumatology clinic over a 6-month period were invited to participate. Cases of secondary RP were excluded. All participants were required to have normal results on nailfold capillary microscopy. Assessment for SFN was accomplished with autonomic reflex screening, which includes quantitative sudomotor axonal reflex test (QSART), and cardiovagal and adrenergic function testing, thermoregulatory sweat test (TST), and quantitative sensory test (QST) for vibratory, cooling, and heat-pain sensory thresholds. Nine female participants with a median age of 38 years (range 21-46 years) and a median symptom duration of 9 years (range 5 months-31 years) were assessed. Three participants had abnormal results on QSART, indicating peripheral sudomotor autonomic dysfunction. Two participants had evidence of large-fiber involvement with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep breathing, Valsalva maneuver, and 70° tilt were normal for all participants. Also, all participants had normal TST results. In total, three of the nine participants had evidence of SFN. The presence of SFN raises the possibility that a subset of patients with primary RP have an underlying, subclinical small-fiber dysfunction. These data open new avenues of research and therapeutics for this common condition.

Small fiber neuropathy: Getting bigger!

“…Autoimmune causes of SFN are commonly seen in Sjögren syndrome, but may also occur in systemic lupus erythematosus, isolated vasculitis of the peripheral nervous system, and primary Raynaud syndrome …”

“…[69][70][71] Autoimmune causes of SFN are commonly seen in Sj€ ogren syndrome, [72][73][74] but may also occur in systemic lupus erythematosus, 75 isolated vasculitis of the peripheral nervous system, 76 and primary Raynaud syndrome. 77 How fibromyalgia and SFN are related has generated considerable controversy. Recently, studies looking for evidence of small nerve fiber neuropathy in primary fibromyalgia patients showed that up to 50% of them had SFN according to IENFD.…”

Analysis of peripheral nerve and autonomic nervous system function and the stage ofmicroangiopathy in patients with secondary Raynaud’s phenomenon in the course of connective tissue diseases

“…Previous research into nervous system disorders in the pathogenesis of RP has been performed on patients with PRP, and these studies have shown that the pathogenesis of PRP is multifactorial and includes the sympathetic peripheral nervous system, central neural abnormalities and local defects. 15,[20][21][22] Mondelli et al showed dysregulation of cholinergic sympathetic fibers innervating the fingers in PRP. Abnormal SSR habituation has suggested that the central mechanism should also be considered.…”

Primary and secondary Raynaud’s phenomenon: does small neuropathy remain the same?

“…Dear Sir, We took great interest in reading Manek and Coll paper's [1], who hypothesize the presence of a small-fiber neuropathy in primary Raynaud's phenomenon (RP). Indeed, we reached similar results testing 12 patients with secondary RP in systemic sclerosis (SSc) when compared to a group of healthy controls [2].…”

“…Peripheral neuropathy is intriguingly common evidence of very different diseases such erythromelalgia [6], connective tissue diseases [2,5,7,8], and RP [1,2,4,5,9]. It seems unlikely that the same postganglionic neuropathy is involved in all these conditions, unless the small fiber neuropathy is considered as a sign of neuropeptidic dysfunction that may manifest in different pathophysiologic ways thereby leading to a different clinical presentation.…”