Reduction of skin innervation is associated with a severe fibromyalgia phenotype

Dimitar Evdokimov, Johanna Frank, Alexander Klitsch, Stefan Unterecker, Bodo Warrings, Jordi Serra, Aikaterini Papagianni, Nadine Saffer, Caren Meyer zu Altenschildesche, Daniel Kampik, Rayaz Malik, Claudia Sommer, Nurcan Üçeyler

Research output: Contribution to journalArticle

Abstract

Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MD-P: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. ANN NEUROL 2019.

Original languageEnglish
JournalAnnals of Neurology
DOIs
Publication statusPublished - 1 Jan 2019

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Fibromyalgia
Phenotype
Skin
Nerve Fibers
Pain
Touch
Evoked Potentials
Pathology
Biopsy
Neurophysiology
Paresthesia
Major Depressive Disorder
Neurologic Examination
Skin Tests
Confocal Microscopy
Chronic Pain
Anxiety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Evdokimov, D., Frank, J., Klitsch, A., Unterecker, S., Warrings, B., Serra, J., ... Üçeyler, N. (2019). Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Annals of Neurology. https://doi.org/10.1002/ana.25565

Reduction of skin innervation is associated with a severe fibromyalgia phenotype. / Evdokimov, Dimitar; Frank, Johanna; Klitsch, Alexander; Unterecker, Stefan; Warrings, Bodo; Serra, Jordi; Papagianni, Aikaterini; Saffer, Nadine; Meyer zu Altenschildesche, Caren; Kampik, Daniel; Malik, Rayaz; Sommer, Claudia; Üçeyler, Nurcan.

In: Annals of Neurology, 01.01.2019.

Research output: Contribution to journalArticle

Evdokimov, D, Frank, J, Klitsch, A, Unterecker, S, Warrings, B, Serra, J, Papagianni, A, Saffer, N, Meyer zu Altenschildesche, C, Kampik, D, Malik, R, Sommer, C & Üçeyler, N 2019, 'Reduction of skin innervation is associated with a severe fibromyalgia phenotype', Annals of Neurology. https://doi.org/10.1002/ana.25565
Evdokimov D, Frank J, Klitsch A, Unterecker S, Warrings B, Serra J et al. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Annals of Neurology. 2019 Jan 1. https://doi.org/10.1002/ana.25565
Evdokimov, Dimitar ; Frank, Johanna ; Klitsch, Alexander ; Unterecker, Stefan ; Warrings, Bodo ; Serra, Jordi ; Papagianni, Aikaterini ; Saffer, Nadine ; Meyer zu Altenschildesche, Caren ; Kampik, Daniel ; Malik, Rayaz ; Sommer, Claudia ; Üçeyler, Nurcan. / Reduction of skin innervation is associated with a severe fibromyalgia phenotype. In: Annals of Neurology. 2019.
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abstract = "Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63{\%} of FMS patients (MD-P: 10{\%}, controls: 18{\%}; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. ANN NEUROL 2019.",
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AU - Serra, Jordi

AU - Papagianni, Aikaterini

AU - Saffer, Nadine

AU - Meyer zu Altenschildesche, Caren

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AB - Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MD-P: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. ANN NEUROL 2019.

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