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Intraepidermal Nerve Fiber Density: Diagnostic and Therapeutic Relevance in the Management of Chronic Pruritus: a Review

View Article: PubMed Central - PubMed

ABSTRACT

In recent years, measurement of the intraepidermal nerve fiber (IENF) density has gained relevance in the diagnostics of chronic pruritus. This method allows the objectification and quantification of a small-fiber neuropathy, which may manifest clinically with pruritus, pain or dysesthetic sensory symptoms, such as burning, stinging and tingling sensations or numbness. Upon suspicion of a small-fiber neuropathy as a cause for chronic pruritus, targeted diagnostic procedures are essential for the early detection of the neuroanatomical changes. After a punch biopsy of the lower leg, the obtained tissue undergoes an immunofluorescence staining process with a primary antibody against the protein gene product 9.5. The IENFs can thus be detected and are quantified according to pre-determined guidelines based on an international consensus. In addition to morphological changes, functional impairment of small-fibers can be assessed using quantitative sensory testing by assessing detection and pain thresholds of various thermal and mechanic modalities. This method, however, is time-consuming and requires a specialized investigator, and thus it is not routinely used in the diagnostic investigation of chronic pruritus. Diagnosing a small-fiber neuropathy underlying chronic pruritus has therapeutic relevance. If possible, the underlying cause of the neuropathy should be treated. Alternatively, symptomatic therapy options include topical (capsaicin) and systemic (anticonvulsants and/or antidepressants) agents. Chronification processes may lead to refractory pruritus, and thus treatment should be initiated as soon as possible. The aim of this review is to present and discuss the measurement of the IENF density as a diagnostic tool and its role in the management of patients with chronic pruritus. A brief case report is presented to better illustrate the role of this diagnostic method in the clinical setting.

No MeSH data available.


PGP 9.5 intraepidermal nerve fibers. a Example of PGP 9.5 intraepidermal nerve fibers (red arrows). b Only single intraepidermal nerve fibers crossing the dermoepidermal junction (arrowhead) are taken into account. Secondary branching (asterisks) or c fragments (white arrow) are not counted. Magnification: ×200, scale bar 100 µm in (a); ×400, scale bar 100 µm in (b, c). PGP 9.5 protein gene product 9.5
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Fig1: PGP 9.5 intraepidermal nerve fibers. a Example of PGP 9.5 intraepidermal nerve fibers (red arrows). b Only single intraepidermal nerve fibers crossing the dermoepidermal junction (arrowhead) are taken into account. Secondary branching (asterisks) or c fragments (white arrow) are not counted. Magnification: ×200, scale bar 100 µm in (a); ×400, scale bar 100 µm in (b, c). PGP 9.5 protein gene product 9.5

Mentions: Precise instructions on how to quantify the IENFD have been established in an international consensus. Per tissue samples, three sections in high magnification (×200–400) are considered. Only single intraepidermal nerve fibers that cross the dermoepidermal junction are taken into account while secondary branching or fragments are not counted. The IENFD is then determined by dividing the number of intraepidermal nerve fibers crossing the dermoepidermal junction to the length of the dermoepidermal junction (Fig. 1) [16, 17].Fig. 1


Intraepidermal Nerve Fiber Density: Diagnostic and Therapeutic Relevance in the Management of Chronic Pruritus: a Review
PGP 9.5 intraepidermal nerve fibers. a Example of PGP 9.5 intraepidermal nerve fibers (red arrows). b Only single intraepidermal nerve fibers crossing the dermoepidermal junction (arrowhead) are taken into account. Secondary branching (asterisks) or c fragments (white arrow) are not counted. Magnification: ×200, scale bar 100 µm in (a); ×400, scale bar 100 µm in (b, c). PGP 9.5 protein gene product 9.5
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5120635&req=5

Fig1: PGP 9.5 intraepidermal nerve fibers. a Example of PGP 9.5 intraepidermal nerve fibers (red arrows). b Only single intraepidermal nerve fibers crossing the dermoepidermal junction (arrowhead) are taken into account. Secondary branching (asterisks) or c fragments (white arrow) are not counted. Magnification: ×200, scale bar 100 µm in (a); ×400, scale bar 100 µm in (b, c). PGP 9.5 protein gene product 9.5
Mentions: Precise instructions on how to quantify the IENFD have been established in an international consensus. Per tissue samples, three sections in high magnification (×200–400) are considered. Only single intraepidermal nerve fibers that cross the dermoepidermal junction are taken into account while secondary branching or fragments are not counted. The IENFD is then determined by dividing the number of intraepidermal nerve fibers crossing the dermoepidermal junction to the length of the dermoepidermal junction (Fig. 1) [16, 17].Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

In recent years, measurement of the intraepidermal nerve fiber (IENF) density has gained relevance in the diagnostics of chronic pruritus. This method allows the objectification and quantification of a small-fiber neuropathy, which may manifest clinically with pruritus, pain or dysesthetic sensory symptoms, such as burning, stinging and tingling sensations or numbness. Upon suspicion of a small-fiber neuropathy as a cause for chronic pruritus, targeted diagnostic procedures are essential for the early detection of the neuroanatomical changes. After a punch biopsy of the lower leg, the obtained tissue undergoes an immunofluorescence staining process with a primary antibody against the protein gene product 9.5. The IENFs can thus be detected and are quantified according to pre-determined guidelines based on an international consensus. In addition to morphological changes, functional impairment of small-fibers can be assessed using quantitative sensory testing by assessing detection and pain thresholds of various thermal and mechanic modalities. This method, however, is time-consuming and requires a specialized investigator, and thus it is not routinely used in the diagnostic investigation of chronic pruritus. Diagnosing a small-fiber neuropathy underlying chronic pruritus has therapeutic relevance. If possible, the underlying cause of the neuropathy should be treated. Alternatively, symptomatic therapy options include topical (capsaicin) and systemic (anticonvulsants and/or antidepressants) agents. Chronification processes may lead to refractory pruritus, and thus treatment should be initiated as soon as possible. The aim of this review is to present and discuss the measurement of the IENF density as a diagnostic tool and its role in the management of patients with chronic pruritus. A brief case report is presented to better illustrate the role of this diagnostic method in the clinical setting.

No MeSH data available.