Toxic neuropathy refers to neuropathy caused by drug ingestion, drug or chemical abuse, or industrial chemical exposure from the workplace or the environment. Distal axonopathy, causing dying-back axonal degeneration, is the most common form.

Signs and symptoms

Patients with neuropathy typically present with symptoms of pain, tingling, or numbness in their feet, consistent with dysfunction affecting the longest and largest fibers of the peripheral nervous system (PNS). Other manifestations of neurologic dysfunction that may be present include the following:

Hypohidrosis or hyperhidrosis

Diarrhea or constipation

Urinary incontinence or retention

Gastroparesis

Sicca syndrome

Blurry vision

Facial flushes

Orthostatic intolerance

Sexual dysfunction

Cramping

Tachycardia

Rapid alterations in blood pressure

During physical examination, the following symptoms of polyneuropathy may be found:

Sensory loss in a stocking-glove distribution

Distal to proximal progression: Consistent with the commencement of axonal degeneration

Early loss of symmetrical ankle jerk

Motor dysfunction (eg, abnormal gait and foot drop): In severe cases

Central nervous system (CNS) disease can manifest as follows:

Corticospinal tract disease: Hyperreflexia, Babinski responses, and stiff-leg ataxic gait

Dorsal column degeneration: Diffusely decreased proprioceptive and vibratory sensations and gait ataxia

The following examples list the neuropathic signs and symptoms associated with specific toxins:

Thallium: Acute intoxication leads to pain and paresthesias in the distal extremities followed by weakness and eventual atrophy; autonomic dysfunction also may be part of the clinical syndrome; peripheral reflexes are preserved

Dimethylaminopropionitrile (DMAP): Industrial exposure has led to prominent urinary and sexual dysfunction, as well as to distal sensory neuropathy

Alcohol: Ataxia and other systemic symptoms may accompany dysesthesia and weakness of the lower extremities

Carbon disulfide: Reduced or absent sensory nerve action potentials (SNAPs) are common; conduction velocities are usually normal, but they may be borderline low owing to selective involvement of large fibers

Ethylene oxide (EtO): Symptoms suggestive of neuropathy, such as numbness and weakness of extremities, leg cramps, and gait difficulties, are reported mostly after long-term EtO exposures

Mercury: Reportedly causes reduced strength and coordination, tremor, impaired sensation, and higher prevalence of Babinski and snout reflexes

Lead: Acute, high-level exposure can reportedly cause motor neuropathy with minimal sensory involvement and, in rare cases, wrist drop; chronic, lower-level exposures cause axonal dying back neuropathies that appear similar to neuropathies from diabetes or alcohol

See Clinical Presentation for more detail.

Diagnosis

Take a thorough medical history, including the patient’s occupational and environmental history, to consider all sources of exposure to all possible agents. List details of all jobs and specific tasks within these jobs, as well as when various symptoms and medical problems began for the patient.

Quantitative sensory testing in the diagnosis of neuropathy includes the following:

Vibration threshold

Thermal threshold

Portable motor and sensory latency

Current perception threshold (CPT)

Other studies that help to prove the presence of neuropathy include the following:

Intraepidermal nerve fiber density (IENF)

Sympathetic skin reflex

Electromyography (EMG)

Nerve conduction

Laboratory studies in patients with neuropathy can include the following:

Glucose tolerance

Serum, urine, or blood

Vitamin B-12

Monoclonal gammopathy of unknown significance

Axonal neuropathy

Cryoglobins and hepatitis C evaluation

Immunofixation (for paraneoplastic neuropathy)

Cerebrospinal fluid (CSF) protein level: Usually normal in toxic neuropathy

See Workup for more detail.

Management

In addition to advising the patient to avoid the causative drug or occupational or environmental toxin, management of toxic neuropathy can include the following:

Nonpharmacologic measures: Cool soaks, heat, massage, elevation or lowering of the limbs, and/or exercise

Tricyclic antidepressants

Anticonvulsants

Opiates

Topical capsaicin cream

Consistent follow-up care with a neurologist is necessary to monitor the progress of neurologic findings. Follow-up with an occupational medicine specialist may be important to assist with return to work and reduction of exposure.

See Treatment for more detail.