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February 2001
Answer: Peripheral neuropathy; neuropathic pain
At the time of the visit to the clinic John rates his pain as a “6” on a scale of 1 to 10. He describes the pain as a burning sensation in the soles of both feet. On physical examination his gait is tentative, and he is unable to walk on his heels. His deep tendon reflexes are decreased (+2/5), and equal throughout. He is unable to dorsiflex his feet past 90 degrees. On sensory examination the pain increases when the soles of his feet are touched, but his cranial nerve and motor function appear intact.
Individuals with HIV infection are at risk for developing various types of peripheral neuropathy, including Guillain-Barré syndrome, ganglioneuritis, sensory axonal neuropathy, lumbosacral polyradiculoneuropathy, chronic inflammatory demyelinating polyneuropathy, and nucleoside-related neuropathy. The most common type of neuropathy that affects HIV-infected individuals is a painful sensory axonal neuropathy. Adults are affected more frequently than children.
Neuropathic pain is caused by altered excitability of the peripheral or central nervous system, usually caused by dysfunction or injury. It is frequently described as a burning, stabbing or shooting sensation. Pain is felt along the distribution of the peripheral nerves. A complete neurologic exam is essential to evaluate sensory, motor, cranial nerve, deep tendon reflex, cerebellar, cognitive and emotional function. Sensory evaluation may demonstrate hyperalgesia (increased sensitivity to pain), or allodynia (pain caused by benign stimuli such as touch). Motor function is often impaired, and patients may have difficulty ambulating or bearing weight. Distal weakness may be present. Deep tendon reflexes may be diminished or absent in the affected extremities. Foot drop may occur in advanced cases.
The etiology of peripheral neuropathy in HIV-infected individuals is varied. At the cellular level, HIV can generate a tissue-specific autoimmune attack on the peripheral nerves. When this occurs, the disease itself is the cause of the neuropathy. Other viruses also have been implicated in causing peripheral neuropathy. The reactivation of varicella-zoster virus results in herpes zoster infection (shingles), and the patient may experience neuropathic pain along the involved sensory dermatome(s). Cytomegalovirus-related polyradiculoneuropathy (inflammation of the nerve roots) and acute febrile polyneuritis (Guillain-Barré syndrome) also cause peripheral neuropathy to occur. HIV-infected children who are deficient in vitamin B12 or pyridoxine may develop distal polyneuropathy. In addition, the use of antiretroviral nucleoside analogues may exacerbate or trigger peripheral neuropathy in patients.
Diagnosis of peripheral neuropathy is generally made on the basis of physical findings and diagnostic studies. At the initial sign of neuropathy, exposure to peripheral neurotoxins should be identified. Agents that are neurotoxic and are often used in patients with HIV include isoniazid, pyridoxine, ethambutol, metranidazole and nucleoside analogs. Nerve conduction studies may be required to determine whether the neuropathy is demyelinating or axonal in order to determine therapy. Nerve biopsy can also be performed if the clinical and electrodiagnostic studies are not conclusive and the patient continues to have pain and physical complaints that are a hindrance to daily activities.
Opioid analgesics, such as acetaminophen with codeine, or acetaminophen with hydrocodone, may be useful in partially controlling neuropathic pain, but the addition of co-analgesic adjuvant drugs, such as antidepressant or anticonvulsant medications, may boost the effect. Amitryptyline and carbamazepine provide analgesia by blocking re-uptake of serotonin and norepinephrine, possibly slowing the transmission of pain signals. Clonidine is an alpha-agonist that modulates ascending pain sensations. The combination of opioids and adjuvant medications gives the patient the best chance for complete pain relief.
Prior to each dose of medication it is important to have the patient determine their level of pain on a consistent pain rating scale. This will help to determine the degree of baseline pain prior to intervention, and then later to determine pain relief. Often, medication doses must be titrated to achieve optimal pain control, so it is very important to assess the patient’s pain quantitatively and frequently.
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