Sensory neuropathy affecting small unmyelinated nerve fibers can be hard to detect during a standard clinical examination. Measuring the nerve fibers within the epidermis can be used to diagnose the condition and monitor its response to therapy. The sooner that the condition is recognized and treated, the better the patient's long-term outcome.


Conditions associated with loss of small unmyelinated nerve fibers include:

(1) diabetes

(2) HIV infection

(3) cancer chemotherapy


These small fibers can be detected in punch biopsies of skin stained with a neuron-specific immunostain to ubiquitin hydrolase (anti-protein gene product 9.5, or PGP 9.5).


An alternative method is corneal confocal microscopy, which can be used to monitor nerve fibers in the cornea.


Measurement of nerve fiber findings may be reported as:

(1) a linear density (number of fibers per mm)

(2) an area density (number of fibers per square mm)

(3) fiber branch length in microns (using laser scanning confocal microscopy)


Damage to epidermal nerve fibers:

(1) may appear prior to the diagnosis of the underlying condition

(2) tends to parallel the severity of the neuropathy

(3) should stabilize or even improve with effective therapy



• To give reliable results the method must be carefully standardized with sections of a controlled thickness done on punch biopsies from the same area (since nerve fiber density may vary with body site).


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