HIV neuropathy: insights in the pathology of HIV peripheral nerve disease

HIV-associated neuropathies (HIV-N) have become the most frequent neurological disorder associated with HIV infection. The most common forms of HIV-N are the distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN), disorders characterized mostly by sensory symptoms that include spontaneous or evoked pain that follow a subacute or chronic course. The main pathological features that characterize DSP and ATN include "dying back" axonal degeneration of long axons in distal regions, loss of unmyelinated fibers, and variable degree of macrophage infiltration in peripheral nerves and dorsal root ganglia. Marked activation of macrophages as well as the effect of pro-inflammatory cytokines appear to be the main immunopathogenic factors in DSP. Interference with DNA synthesis and mitochondrial abnormalities produced by nucleoside antiretrovirals have been hypothesized as pathogenic factors involved in ATN. The use of skin biopsy has become a useful tool in the evaluation of HIV-N. Reduction in fiber density, increased frequency of fiber varicosities and fiber fragmentation are prominent features of skin biopsies from patients with HIV-N. Other forms of HIV-N include acute or chronic inflammatory polyneuropathies, uncommon disorders that may ocur during seroconversion or early stages of HIV infection. Opportunisitic infections, mostly associated with cytomegalovirus or herpes zoster virus infection occur in late stages of AIDS and produce characteristic clinical features such as mononeuritis multiple or radiculopathies.