@phdthesis{Klitsch2021,
  author    = {Klitsch, Alexander},
  title     = {Corneal and cutaneous factors contributing to small fiber pathology in fibromyalgia syndrome},
  doi       = {10.25972/OPUS-22439},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224398},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {We examined 143 patients suffering from FMS, a syndrome characterized by chronic widespread pain, sleep disturbances, and fatigue. Etiology and pathophysiology of FMS are scarcely understood. In recent years abnormalities of small Aδ- and C-nerve fibers have been found in subgroups of FMS patients. It is yet unclear how such SFP is caused in FMS patients and how it contributes to FMS symptoms. We used CCM to analyze corneal small nerve fibers and associated LC, comparing FMS patients' results to those from 65 healthy controls and 41 disease controls suffering from SFN. We, further, assessed expression levels of mRNA and miRNA in keratinocytes taken from skin punch biopsies of FMS patients and healthy controls kept as monocellular cell cultures. A screening was performed using NGS in a small cohort of 12 FMS patients and 5 healthy controls. Results were validated in larger cohorts by qRT-PCR. As in previous studies IENFD and CNFD were reduced in a subgroup of FMS patients. We found identical LC densities in FMS patients, healthy controls, and SFN patients. The subpopulation of dLCfiber contact in FMS and SFN patients was lower than in healthy controls. Our RNA expression analysis revealed one mRNA that was expressed higher in FMS patients than in controls: PRSS21. We conclude that reduced neurotrophic signaling of LC may contribute to SFP in the cornea. Epidermal PRSS21 expression and dLCfiber contact density are promising biomarker candidates for FMS diagnosis.},
  subject      = {Fibromyalgie},
  language  = {en}
}
@article{EgenolfAltenschildescheKressetal.2021,
  author    = {Egenolf, Nadine and Altenschildesche, Caren Meyer zu and Kreß, Luisa and Eggermann, Katja and Namer, Barbara and Gross, Franziska and Klitsch, Alexander and Malzacher, Tobias and Kampik, Daniel and Malik, Rayaz A. and Kurth, Ingo and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study},
  series = {Therapeutic Advances in Neurological Disorders},
  volume    = {14},
  journal   = {Therapeutic Advances in Neurological Disorders},
  issn      = {1756-2864},
  doi       = {10.1177/17562864211004318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232019},
  year      = {2021},
  abstract  = {Background and aims: Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard. Methods: In this case-control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART). Results: Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70\%) and neurological examination (53/86, 62\%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85\%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16\%) index patients. QST, QSART, and proximal IENFD were of lower impact. Conclusion: We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.},
  language  = {en}
}