Skin biopsy for diagnosis of small fiber neuropathy: a critically appraised topic.
BACKGROUND
Patients with lower extremity sensory symptoms and pain but without clinical or standard neurophysiological examination abnormalities may have a small fiber neuropathy. Skin biopsy with intraepidermal nerve fiber density (IENFD) assessment has been promoted as a diagnostic tool for such patients.


OBJECTIVE
To evaluate the diagnostic utility of skin biopsy with IENFD in patients with suspected small fiber neuropathy.


METHODS
The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology.


RESULTS
One primary article was selected for review. A retrospective study using skin biopsy with IENFD detected abnormalities in 88.1% of 67 patients who had symptoms suggestive of sensory neuropathy but normal nerve conduction studies compared with 10% of healthy controls. Skin biopsy was more often abnormal in this setting than either the clinical examination (signs of small fiber impairment) or quantitative sensory testing but formal evaluation of sensitivity and specificity are compromised by inclusion of the diagnostic tests within the definition of the reference standard. Skin biopsy with IENFD was abnormal in 81% of patients clinically diagnosed with mixed large and small fiber neuropathy, 0/22 patients with large fiber neuropathy and 0/16 patients with nonperipheral neuropathic disorders.


CONCLUSIONS
Detection of reduced IENFD using skin biopsy may be sensitive and specific for clinically-defined syndromes consistent with small fiber neuropathy. Skin biopsy appears to have greater diagnostic utility than the neurologic examination and quantitative sensory testing, both of which rely heavily on subjective patient perception. Prospective studies that evaluate quantitative methodology (rather than modalities that rely on patient report) and do not include the diagnostic tests in the reference standard are needed. Consensus is needed regarding a reference standard definition for small fiber neuropathy.
Hlubocky
Ales
A
Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA.
Wellik
Kay
K
Ross
Mark A
MA
Smith
Benn E
BE
Hoffman-Snyder
Charlene
C
Demaerschalk
Bart M
BM
Wingerchuk
Dean M
DM
D001706:Biopsy; D006801:Humans; D009412:Nerve Fibers / Q000473:pathology*; D009431:Neural Conduction; D009460:Neurologic Examination; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D012680:Sensitivity and Specificity; D012867:Skin / Q000294:innervation* / Q000473:pathology