Symptoms and diagnosis

The primary symptom of peripheral sensory neuropathy is pain, which can range from mild discomfort to a sharp burning or ‘shooting’ sensations. Pain may be constant or may come and go in bursts. Some patients describe a tingling or prickly feeling similar to a limb ‘falling asleep,’ while others say they feel like they are wearing gloves and stockings all the time. Perception of touch, vibration, and temperature may also be altered, and reflexes may stop working normally.

In some cases, the pain may be so severe that patients find it impossible to wear socks and shoes and even the pressure of bedclothes can be unbearable. Some individuals have difficulty walking due to muscle weakness, loss of balance, and reduced sensation in their feet and legs.

The lower extremities are most often affected, starting with the toes and soles of the feet and moving up through the ankles and lower legs. Less commonly, as neuropathy progresses, it may also involve the hands. Symptoms tend to be symmetrical, affecting both sides of the body equally.

Patients with peripheral autonomic neuropathy may develop symptoms including dizziness, fainting due to blood pressure changes, diarrhoea, changes in urination, and sexual dysfunction.

Peripheral neuropathy is diagnosed based on symptoms. Electromyography and nerve conduction studies can also detect nerve problems. A skin-punch biopsy can reveal damaged nerves; antiretroviral toxic neuropathy is typically characterised by damaged axons, the part of the nerve cell that transmits impulses.

Neurological tests and biopsies usually cannot distinguish drug-induced neuropathy from similar nerve damage due to other causes. The best way to confirm the diagnosis is to discontinue a potentially neurotoxic drug and see if symptoms improve.

Testing of blood lactate has been proposed as a method for distinguishing nucleoside reverse transcriptase inhibitor (NRTI)-induced neuropathy from other causes. In one study, 13 out of 15 patients with d4T (stavudine, Zerit)-related neuropathy had an elevated serum lactate level suggestive of mitochondrial toxicity, which was seen in only one person with non-drug-related HIV neuropathy. However, not all patients taking d4T who had elevated lactate levels also had peripheral neuropathy.¹