Abstract
In the last three decades the study of cutaneous innervation through 3 mm-punch-biopsy has provided an important contribution to the knowledge of small fiber somatic and autonomic neuropathies but also of large fiber neuropathies. Skin biopsy is a minimally invasive technique with the advantage, compared to sural nerve biopsy, of being suitable to be applied to any site in our body, of being repeatable over time, of allowing the identification of each population of nerve fiber through its target. In patients with symptoms and signs of small fiber neuropathy the assessment of IntraEpidermal Nerve Fiber density is the gold standard to confirm the diagnosis while the quantification of sudomotor, pilomotor, and vasomotor nerve fibers allows to evaluate and characterize the autonomic involvement. All these parameters can be re-evaluated over time to monitor the disease process and to evaluate the effectiveness of the treatments. Myelinated fibers and their receptors can also be evaluated to detect a “dying back” neuropathy early when nerve conduction study is still normal. Furthermore, the morphometry of dermal myelinated fibers has provided new insight into pathophysiological mechanisms of different types of inherited and acquired large fibers neuropathies. In genetic neuropathies skin biopsy has become a surrogate for sural nerve biopsy, no longer necessary in the diagnostic process, to study genotype–phenotype correlations.
Highlights
In the last three decades, the analysis of cutaneous nerves sampled by means of 3 mm punch biopsy has provided an important contribution to our knowledge of peripheral sensory and autonomic neuropathies [1,2].This because the skin includes a rich network of sensory nerves originating from the dorsal root ganglia and autonomic nerves originating from the postganglionic sympathetic endings.The skin shares with the CNS the embryologic origin from the same layer and represents, beside a physical, chemical, and immunological barrier for the entire body surface, our interface with the outside
The advantages of applying skin biopsy compared to sural nerve analysis are the higher sensibility [12], the minimal invasiveness and the possibility to perform it in any body site and to repeat it over time
This morphological evidence is further corroborated by functional studies that through microneurography demonstrated an abnormal ongoing activity of peripheral C nociceptors and increased mechanical sensitivity in fibromyalgia patients compared to controls [55]
Summary
In the last three decades, the analysis of cutaneous nerves sampled by means of 3 mm punch biopsy has provided an important contribution to our knowledge of peripheral sensory and autonomic neuropathies [1,2]. Due to the close relationship of epidermal nerves with keratinocytes and the presence of common sensory receptors, the epidermis can be considered as a huge sensory organ able to inform our brain on what is happening outside our body and how comfortable, or not, we feel with environmental changes. This implies a continuous flow of information from the periphery to the sensory brain cortex and to limbic areas through the insula (interoception) and to the central autonomic network that through the cutaneous autonomic nerves puts in place emotional and homeostatic responses to outer and inner changes. We assessed the remaining papers based on their relevance to the field and included all the literature that was appropriate for the scheme of this narrative review
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