Neurology 2002;58:115-119
© 2002 American Academy of Neurology
Articles
Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy
M. Polydefkis, MD,
C.T. Yiannoutsos, PhD,
B.A. Cohen, MD,
H. Hollander, MD,
G. Schifitto, MD,
D.B. Clifford, MD,
D.M. Simpson, MD,
D. Katzenstein, MD,
S. Shriver, MS,
P. Hauer, BA,
A. Brown,
A.B. Haidich, MSc,
L. Moo, MD and
J.C. McArthur, MBBS MPH
From the Departments of Neurology (Drs. Polydefkis, Moo, and McArthur, and P. Hauer and A. Brown) and Epidemiology (Dr. McArthur), Johns Hopkins University, Baltimore, MD; Harvard School of Public Health (Dr. Yiannoutsos and A. Haidich) Boston, MA; Department of Neurology (Dr. Schifitto), University of Rochester, NY; Department of Neurology (Dr. Simpson), Mount Sinai School of Medicine, New York, NY; AIDS Clinical Trials Group Operations (S. Shriver), Rockville, MD; Department of Neurology (Dr. Cohen), Northwestern University, Chicago, IL; Department of Neurology (Dr. Katzenstein), Stanford University, Palo Alto, CA; Department of Medicine (Dr. Hollander), University of California, San Francisco; and Department of Neurology (Dr. Clifford), Washington University, St. Louis, MO.
Address correspondence and reprint requests to Dr. M. Polydefkis, Department of Neurology, The Johns Hopkins Hospital, Pathology 509, 600 North Wolfe Street, Baltimore, MD 21287; e-mail: mpolyde{at}jhmi.edu
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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