title: Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy.
abstract: OBJECTIVE
  To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease.
  
  
  BACKGROUND
  SN affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy.
  
  
  METHODS
  Sixty-two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase.
  
  
  RESULTS
  IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time.
  
  
  CONCLUSIONS
  IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials.
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. mpolyde@jhmi.edu
authors.forename: M
authors.initials: M
authors.lastname: Polydefkis
authors.forename: C T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: B A
authors.initials: BA
authors.lastname: Cohen
authors.forename: H
authors.initials: H
authors.lastname: Hollander
authors.forename: G
authors.initials: G
authors.lastname: Schifitto
authors.forename: D B
authors.initials: DB
authors.lastname: Clifford
authors.forename: D M
authors.initials: DM
authors.lastname: Simpson
authors.forename: D
authors.initials: D
authors.lastname: Katzenstein
authors.forename: S
authors.initials: S
authors.lastname: Shriver
authors.forename: P
authors.initials: P
authors.lastname: Hauer
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: A B
authors.initials: AB
authors.lastname: Haidich
authors.forename: L
authors.initials: L
authors.lastname: Moo
authors.forename: J C
authors.initials: JC
authors.lastname: McArthur
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use; D018450:Disease Progression; D004817:Epidermis / Q000294:innervation*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009437:Neuralgia / Q000209:etiology; D009475:Neurons, Afferent / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000473:pathology*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015224:Dideoxynucleosides