Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy

M. Polydefkis, Constantin Yiannoutsos, B. A. Cohen, H. Hollander, G. Schifitto, D. B. Clifford, D. M. Simpson, D. Katzenstein, S. Shriver, P. Hauer, A. Brown, A. B. Haidich, L. Moo, J. C. McArthur

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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.

Original languageEnglish (US)
Pages (from-to)115-119
Number of pages5
JournalNeurology
Volume58
Issue number1
StatePublished - Jan 8 2002
Externally publishedYes

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Nerve Fibers
HIV
Neuralgia
CD4 Lymphocyte Count
Nerve Growth Factor
Pain Measurement
Leg
Clinical Trials
RNA
Physicians
Pain
Unmyelinated Nerve Fibers
Viral Load
Routine Diagnostic Tests
Longitudinal Studies
Disease Progression
Acquired Immunodeficiency Syndrome
Placebos
Biopsy
Skin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Polydefkis, M., Yiannoutsos, C., Cohen, B. A., Hollander, H., Schifitto, G., Clifford, D. B., ... McArthur, J. C. (2002). Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology, 58(1), 115-119.

Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. / Polydefkis, M.; Yiannoutsos, Constantin; Cohen, B. A.; Hollander, H.; Schifitto, G.; Clifford, D. B.; Simpson, D. M.; Katzenstein, D.; Shriver, S.; Hauer, P.; Brown, A.; Haidich, A. B.; Moo, L.; McArthur, J. C.

In: Neurology, Vol. 58, No. 1, 08.01.2002, p. 115-119.

Research output: Contribution to journalArticle

Polydefkis, M, Yiannoutsos, C, Cohen, BA, Hollander, H, Schifitto, G, Clifford, DB, Simpson, DM, Katzenstein, D, Shriver, S, Hauer, P, Brown, A, Haidich, AB, Moo, L & McArthur, JC 2002, 'Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy', Neurology, vol. 58, no. 1, pp. 115-119.
Polydefkis M, Yiannoutsos C, Cohen BA, Hollander H, Schifitto G, Clifford DB et al. Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology. 2002 Jan 8;58(1):115-119.
Polydefkis, M. ; Yiannoutsos, Constantin ; Cohen, B. A. ; Hollander, H. ; Schifitto, G. ; Clifford, D. B. ; Simpson, D. M. ; Katzenstein, D. ; Shriver, S. ; Hauer, P. ; Brown, A. ; Haidich, A. B. ; Moo, L. ; McArthur, J. C. / Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. In: Neurology. 2002 ; Vol. 58, No. 1. pp. 115-119.
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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.",
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AU - Yiannoutsos, Constantin

AU - Cohen, B. A.

AU - Hollander, H.

AU - Schifitto, G.

AU - Clifford, D. B.

AU - Simpson, D. M.

AU - Katzenstein, D.

AU - Shriver, S.

AU - Hauer, P.

AU - Brown, A.

AU - Haidich, A. B.

AU - Moo, L.

AU - McArthur, J. C.

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N2 - 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.

AB - 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.

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