Reduced association between dendritic cells and corneal sub-basal nerve fibers in patients with fibromyalgia syndrome.

Alexander Klitsch,Claudia Sommer,Daniel Kampik,Dominique Thomas,Nurcan Üçeyler,Caren Meyer Zu Altenschildesche,Rayaz A Malik,Marco Sisignano,Nadine Saffer,Dimitar Evdokimov,Johanna Frank

doi:10.1111/jns.12360

Abstract

In our study, we aimed at investigating corneal langerhans cells (LC) in patients with fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) as potential contributors to corneal small fiber pathology. We enrolled women with FMS (n = 134) and SFN (n = 41) who underwent neurological examination, neurophysiology, prostaglandin analysis in tear fluid, and corneal confocal microscopy (CCM). Data were compared with those of 60 age-matched female controls. After screening for dry eye disease, corneal LC were counted and sub-classified as dendritic (dLC) and non-dendritic (ndLC) cells with or without nerve fiber association. We further analyzed corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Neurological examination indicated deficits of small fiber function in patients with SFN. Nerve conduction studies were normal in all participants. Dry eye disease was more prevalent in FMS (17%) and SFN (28%) patients than in controls (5%). Tear fluid prostaglandin levels did not differ between FMS patients and controls. While corneal LC density in FMS and SFN patients was not different from controls, there were fewer dLC in association with nerve fibers in FMS and SFN patients than in controls (P < .01 each). Compared to controls, CNFL was lower in FMS and SFN patients (P < .05 each), CNFD was lower only in FMS patients (P < .05), and CNBD was lower only in SFN patients (P < .001). There was no difference in any CCM parameter between patients with and without dry eyes. Our data indicate changes in corneal innervation and LC distribution in FMS and SFN, potentially based on altered LC signaling.

Highlights

We examined corneal langerhans cells (LC) and sub-basal nerve fibers in fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) patients compared to healthy controls and report on lower numbers of dLC in association with nerve fibers in FMS and SFN patients
We further show lower CNBD in patients with SFN compared to FMS independent of dry eye disease (DED)
We assume that the immune cells observed via confocal microscopy (CCM) are Langerhans cells since corneal epithelial dendritic cells exclusively resemble LC in terms of antigen expression and ultra-structural morphology in healthy human eyes.[40]

Summary

| INTRODUCTION

Small nerve fiber pathology was found in subgroups of patients with fibromyalgia syndrome (FMS).[1,2,3,4,5,6,7,8,9,10,11,12] Applying corneal confocal microscopy (CCM), corneal denervation was reported in FMS patients.[9,13,14]. Integrity of the corneal sub-basal nerve plexus is regulated by interactions between immune cells and nerve fiber endings.[21,22] Their communication is crucial controlling the corneal immune status.[23,24] A disruption of these fine-tuned neuro-immune interactions may alter corneal innervation. They are promising targets for pathophysiological mechanisms in small fiber pathology. In this prospective and controlled study, we investigated corneal immune cells of patients with FMS compared to SFN and healthy controls. We report a reduction of nerve fiber associated LC in patients with FMS compared to healthy controls and even more so in patients with SFN which may contribute to corneal small fiber pathology

| Study participants

| RESULTS

| DISCUSSION

Findings

CONFLICT OF INTEREST