What are the etiologies of distal symmetric painful polyneuropathy?
• Diabetes is the most commonly established cause. While it is not clear why pain severity varies among people with diabetic neuropathy, evidence of some genetic factors is emerging.
• There is also evidence that prediabetes (impaired glucose tolerance or impaired fasting glucose) is prevalent among nondiabetic people with distal symmetric painful polyneuropathy, often in the context of the metabolic syndrome, or a combination of glucose dysmetabolism, hypertension, hyperlipidemia, and obesity. For this reason, a 2-hour oral glucose tolerance test and fasting lipid panel are commonly performed in nondiabetic people presenting with painful polyneuropathy. In such cases one can only say that there is an association between the metabolic syndrome or prediabetes and neuropathy, but given the fact that these are modifiable risk factors for vascular events, it is important to consider the development of unexplained painful polyneuropathy as an opportunity to test for these conditions.
• Infections: Most commonly, chronic hepatitis C and HIV.
• Neurotoxins: Alcohol is perhaps the most common neurotoxin to cause a painful polyneuropathy. The other major class is medications. Principal among these are antiretroviral drugs and several cancer treatments, including oxaliplatin, cis-platinum, and taxanes.
• Ιnflammatory disorders: Most notably Sjogren’s syndrome, which can cause either a non-length-dependent ganglionopathy or a distal symmetric sensory polyneuropathy.
• The precise cause of distal symmetric painful polyneuropathy is often undiscovered despite appropriate investigations.