Background & Aims

Fibromyalgia syndrome (FMS) is a chronic pain condition estimated to affect between 2% and 4% of the general population with a female:male ratio of 1-2:1. Although little is known about the pathophysiology of FMS, there is evidence for a peripheral nervous system involvement with numerous studies confirming small fiber pathology in 30 to 70% of women with FMS. However, respective data from men with FMS are missing and to date the involvement of small nerve fibers in male patients with FMS is unknown. In this prospective single-center case-control study, we pioneer the investigation of small fiber impairment in a cohort of men with FMS on a morphological and functional level.

Methods

A cohort of 42 male FMS patients underwent a detailed pain-related interview and neurological examination, questionnaire assessment, nerve conduction studies, and four specialized small fiber tests: quantitative sensory testing (QST) including C-tactile afferents, skin punch biopsy, and corneal confocal microscopy (CCM). Data were compared with those of healthy male control subjects.

Results

Neurological examination and nerve conduction studies were normal in all FMS patients. Men with FMS mainly reported of generalized and constant pressing pain with additional pain attacks. Compared with control subjects, QST revealed that men with FMS had impaired small nerve fiber function with elevated cold (p<0.05) and warm (p<0.001) detection thresholds, increased mechanical pain threshold (p<0.05) and an impairment of C-tactile afferents (p<0.05). Intraepidermal nerve fiber density (IENFD) was reduced at ?1 biopsy site in 83% of men with FMS (controls: 49%). Corneal nerve fiber density was also reduced in male FMS patients versus healthy men (p<0.01), indicating widespread small nerve fiber damage. In comparison to men with FMS with a normal skin innervation, those with pathological reduction in skin innervation at ?1 biopsy site had a higher clinical Widespread Pain Index (p<0.05) indicating a relationship between symptom load and severity of peripheral denervation.

Conclusions

Our study is the first to investigate small nerve fibers in a cohort of men with FMS on a morphological and functional level. We show widespread small nerve fiber dysfunction and pathology in distal and proximal skin and cornea in the majority of male FMS patients. Furthermore, the severity of skin denervation correlated with the severity of pain and male patients with FMS have a distinct pain phenotype and pattern of skin denervation which differs from women with FMS.

References

1. Häuser W, Fitzcharles M. Facts and myths pertaining to fibromyalgia. Dialogues in Clinical Neuroscience. 2018;20:53–62.
2. Grayston R, Czanner G, Elhadd K, et al. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis. Seminars in Arthritis and Rheumatism. 2019;48:933-940.
3. Evdokimov D, Frank J, Klitsch A, et al. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Annals of Neurology. 2019;86:504-516.

Presenting Author

Betty Feulner

Poster Authors

Betty Feulner

University of Würzburg

Lead Author

E-mail

Franziska Gross

MD

Department of Neurology, University of Würzburg, Germany

Lead Author

E-mail

Dimitar Evdokimov

MD

Department of Neurology, University of Würzburg, Germany

Lead Author

E-mail

Rayaz A. Malik

MD

Weill Cornell Medicine – Qatar, Education City, Qatar Foundation, Doha, Qatar

Lead Author

E-mail

Daniel Kampik

MD

Department of Ophthalmology, University of Würzburg, Germany

Lead Author

E-mail

Nurcan Üçeyler

MD

Department of Neurology, University of Würzburg, Germany

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Fibromyalgia