Primary Raynaud Phenomenon and Small-Fiber Neuropathy: Is There a Connection? A Pilot Neurophysiologic Study

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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.