title: Painful sensory neuropathy: prospective evaluation using skin biopsy.
abstract: OBJECTIVE
  In patients presenting with painful, burning feet with minimal signs of neuropathy, the following questions were addressed: 1) How many of these patients have a peripheral neuropathy? 2) What is the role of skin biopsy in establishing a diagnosis of neuropathy? 3) What conditions are associated with the neuropathy? and 4) What laboratory studies are useful in this patient population?
  
  
  METHODS
  A total of 117 consecutive patients referred for evaluation were prospectively studied. All underwent nerve conduction studies (NCS) and a battery of blood tests, including antinerve antibodies. If NCS were normal, a punch biopsy of the skin of the distal leg was performed to ascertain the intraepidermal nerve fiber (IENF) density. In a subset of 32 patients, the sensitivity of skin biopsy was compared to quantitative sudomotor axon test (QSART) and quantitative sensory tests (QST).
  
  
  RESULTS
  Three groups emerged. Group 1, with abnormal NCS (n = 60, 34 F/26 M, mean age 60 +/- 14 years), represented 51% of the cohort. The majority had neuropathies of undetermined cause, but 18 (30%) had associated conditions. Group 2, with normal NCS and reduced IENF density (n = 44, 29 F/15 M, mean age 57 +/- 14 years), represented 38% of the cohort. Three in this group had associated conditions. Group 3, with normal NCS and IENF density (n = 13, 6 F/7 M, mean age 53 +/- 13 years), represented 11% of the cohort; most had no diagnoses but two had MS. In a comparative subset analysis, skin biopsy was more sensitive than QSART or QST in diagnosing a neuropathy.
  
  
  CONCLUSIONS
  Patients presenting with painful feet are heterogeneous, consisting of both large and small fiber sensory neuropathies. In rare cases, a central cause for pain can be found. Over one-third of patients required a skin biopsy to diagnose a small fiber sensory neuropathy. A limited battery of blood tests facilitated diagnosis, but serum antinerve antibodies were not helpful.
authors.affiliation: Department of Neurology, The Ohio State University, Columbus 43210, USA. periquet1@osu.du
authors.forename: M I
authors.initials: MI
authors.lastname: Periquet
authors.forename: V
authors.initials: V
authors.lastname: Novak
authors.forename: M P
authors.initials: MP
authors.lastname: Collins
authors.forename: H N
authors.initials: HN
authors.lastname: Nagaraja
authors.forename: S
authors.initials: S
authors.lastname: Erdem
authors.forename: S M
authors.initials: SM
authors.lastname: Nash
authors.forename: M L
authors.initials: ML
authors.lastname: Freimer
authors.forename: Z
authors.initials: Z
authors.lastname: Sahenk
authors.forename: J T
authors.initials: JT
authors.lastname: Kissel
authors.forename: J R
authors.initials: JR
authors.lastname: Mendell
mesh_terms: D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D003943:Diagnostic Techniques, Neurological; D004817:Epidermis / Q000294:innervation; D005260:Female; D005528:Foot; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications; D009412:Nerve Fibers / Q000473:pathology; D009422:Nervous System Diseases / Q000175:diagnosis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D009431:Neural Conduction; D010146:Pain / Q000503:physiopathology*; D011446:Prospective Studies; D012677:Sensation; D012867:Skin / Q000473:pathology*