Toxic and drug-induced neuropathies

Peripheral neuropathy is a side effect of several commonly used drugs. The correct diagnosis of medication-induced neuropathy can be difficult, and a high index of suspicion is required to identify a medication as the cause of peripheral neuropathy. This is an important issue, because a delay in recognizing a toxic neuropathy may lead to an unfavorable course and incomplete recovery after drug withdrawal or the beginning of treatment. However, the temporal association between the use of a drug and the onset of peripheral neuropathy does not necessarily indicate a causal relationship. Criteria are proposed to clarify this issue. An association with a medication is considered likely when a strong dose response relationship is present, clinical manifestations are consistent and occur rapidly after drug administration is initiated, amelioration is obtained after drug withdrawal, and similar pathological alterations can be observed in human biopsies and animal models. Further studies are essential to clarify the important issue of the clinical relevance of proteasome inhibitors' peripheral neurotoxicity and to define the mechanisms of this toxic effect, because it potentially may be a dose-limiting side effect in the future clinical use of these substances. © 2007 Elsevier Inc. All rights reserved.