Quantitative and qualitative normative dataset for intraepidermal nerve fibers using skin biopsy.

BACKGROUND: Skin biopsy is the most relevant tool to diagnose small-fiber neuropathy. A well-documented normal dataset for intraepidermal nerve fiber in the distal leg is required to improve its diagnostic value. METHODS: Three hundred healthy subjects were enrolled in the study, after clinical and biological screening to exclude neurological and systemic pathologies. A distal leg biopsy was taken and intraepidermal nerve fiber density after protein gene product-9.5 immunocytochemistry with brightfield microscopy was determined. Morphological variations of intraepidermal nerve fibers, previously described in small-fiber neuropathies, were analyzed. One hundred biopsies were also analyzed at the ultrastructural level. FINDINGS: The median number of fibers was lower in men compared to women and decreased with age. Using statistical modeling taking into account age and gender, we calculated the 5th percentile of intraepidermal nerve fiber density as follows: 7.6156-0.0769 x age (years) + 1.5506 x gender (woman = 1; man = 0). We observed a low frequency of large swellings or horizontal branchings but an increasing frequency of small swellings of intraepidermal nerve fibers and irregular distribution along the dermal-epidermal junction with age. Axonal diameter of unmyelinated fibers of the papillary dermis did not vary with age or gender. Ultrastructural analysis also showed that fiber endings in close apposition to Merkel cells should not be mistaken for small-fiber swellings. CONCLUSIONS: Our dataset allows accurate calculation of the normal density of intraepidermal nerve fibers for each year of age and provides original morphological observations that improve the diagnostic value of skin biopsy in the distal leg for small-fiber neuropathy.

[Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017, overview of systematic review articles and overview of studies on small fiber neuropathy in FMS subgroups]. / Ätiologie und Pathophysiologie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten sowie eine Übersicht über Studien zur Kleinfaserpathologie bei Subgruppen des FMS.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was planned for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective population-based studies and systematic reviews with meta-analyses of case control studies were taken into consideration for the statements. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The statements were generated by multiple step formalized procedures. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS: Current data do not enable identification of distinct factors in the etiology and pathophysiology of fibromyalgia syndrome. Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases, gene polymorphisms, life style factors (e.g. smoking, obesity and lack of physical activity), depressive disorders as well as physical and sexual abuse in childhood and adulthood. CONCLUSION: Fibromyalgia syndrome is most probably the end result of various pathogenetic factors and pathophysiological mechanisms.