Anti-tumor necrosis factor alpha (anti-TNF α) and demyelinating neuropathy, optic neuropathy (golimumab)
TNF-α inhibitors such as infliximab, adalimumab, certolizumab, and etanercept are commonly used in the treatment of RA. Studies have shown that patients exposed to TNF-α inhibitors have a higher risk of central and peripheral demyelinating disorders.
Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases - PMC
Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications
Among TNF-α inhibitor-related autoimmune disorders (TAIRIDs), the most frequently reported are psoriasis (PsO), inflammatory bowel diseases (IBD), central nervous system (CNS) demyelinating diseases, interstitial lung disease (ILD), vasculitis and lupus. The diagnosis of TAIRID is supported by the temporal relationship between disease onset in patients without previous disease and improvement after discontinuation of the TNF-α inhibitor.
With a frequency that is not particularly high but also not negligible, TNF-α inhibitors can favour the development of systemic and organ-specific autoimmune-mediated disorders.
Acrylamide, Allyl chloride, Arsenic, Bortezomib, 2-t-Butylazo-2-hydroxy, Capsaicin, Carbon disulfide, Carbamate pesticides, Ciguatoxin, Chloramphenicol, Chloroquine, Cisplatin, Colchicine, Dapsone, Dioxin, Digoxin, Dimethyl aminopropionitrile, Diphtheria toxin, Disulfiram, Ethambutol, Ethylene oxide, flecainide. Gold salts, Hexachlorophene, n-Hexane, Hydralazine, Hydrazine, Hymenoptera stings, Isoniazid, IFN-alpha, Karwinskia humboldtiana, Lead, Lithium, Mercury (elemental), Methyl bromide, Metronidazole, Misonidazole, Nitrofurantoin, Nitrous oxide, Nucleoside analogues, Organophosphorus compounds, Oxaliplatin, Perhexiline maleate, Phenytoin, Podophyllotoxin, Polychlorinated biphenyls, Pyridoxine, Rabies vaccine, Suramin, Statins, Taxanes, Thalidomide, Thallium, Vacor, rat poison, Vidarabine, and Vinca alkaloids.
Hydralazine is an antihypertensive agent used commonly in intensive care settings because of its rapid onset of action and short half-life, but it has been known to cause pyridoxine deficiency–related neuropathy.
Demyelinating Neuropathy: Amiodaraone (also causes bluish discoloration of skin - photosensitive), chlorquine, tacrolimus,perhexiline, procainamide, zelmidine, tocilizumab
Drug-Induced Peripheral Neuropathy: A Narrative Review - PMC
Several agents (diphtheria, arsenic, suramin) may be associated with findings suggestive of an acute toxic demyelinating neuropathy (presumably not inflammatory). Exposure to these agents can result in a disabling acute or subacute diffuse, predominantly motor neuropathy with areflexia, and sometimes, cranial nerve dysfunction. This condition resembles the Guillain-Barre´ syndrome. Recovery is usually satisfactory and can be rapid in mild cases. Subacute or chronic predominantly demyelinating neuropathy characterized by conduction slowing and with moderate axonal degeneration is associated with therapy with perhexiline maleate or amiodarone. The conduction slowing may reflect preferential loss of the largest, fastest conducting motor axons.
This common morphologic reaction is encountered after chronic or subacute exposure to many pharmaceutical and occupational agents. Some also cause severe systemic illness (thallium, arsenic), while others are well tolerated and patients feel well (acrylamide, pyridoxine). Most are associated with chronic low-level exposure: onset is insidious, and acral paresthetic sensory symptoms are prominent. With few exceptions (thallium, nucleosides, arsenic) pain is not a dominant feature. A few patients have weakness as an overriding complaint (hexane sniffers, dapsone, disulfiram, lead, organophosphates). The neurophysiologic profile includes low-amplitude sensory or motor responses, minimal decrease in conduction velocity, and denervation potentials in distal limb muscles. This picture is similar to that seen in other metabolic distal axonopathies; it is helpful in ruling out demyelinating and multifocal axonal disorders but is of limited differential diagnostic value. The neuropathologic substrate is nonspecific degeneration of distal regions of axons in the CNS and peripheral nervous system. Nerve biopsy is rarely justified in evaluating toxic neuropathy. Noninvasive quantitative sensory testing, especially vibration, while of little differential diagnostic value, is of considerable help in monitoring recovery; in many instances, improvement can be documented before it is apparent to the patient. Quantitative sensory testing is especially useful in repeated screening of large industrial populations at risk for toxic neuropathy.
Metronidazole is a member of the nitroimidazole group. It is associated with painful paresthesias in a length-dependent pattern. It results in loss of large and small fiber sensory modalities, distal weakness and sometimes autonomic dysfunction as well. There is axonal degeneration of large myelinated fibers, axonal swellings. NCS/EMG: low amplitude or unobtainable SNAPs with normal or slightly reduced CMAP amplitudes. The cumulative dose at which neuropathy occurs is wide, ranging from 3.6 to 228 gm. Neuropathy is know to occur in individuals receiving greater than 1.5 gm daily of metronidazole for 30 or more days. The neuropathy improves after discontinuation of the drug, but there is a coasting effect such that the symptoms may continue to worsen for several weeks. Some patient are left with residual sensory symptoms. Of note metronidazole is also associated with encephalopathy which resembles thiamine deficiency.
Misonidazole: same as metronidazole.
Chloroquine and hydroxychloroquine have amphiphilic properties and may lead to drug-lipid complexes that are indigestible and result in accumulation of autophagic vacuoles. It can cause paresthesia and pain with loss of large and small fiber sensory modalities and distal weakness in a length-dependent pattern; superimposed myopathy leading to proximal weakness. It causes axonal degeneration with autophagic vacuoles in nerves as well as muscle fibers. EMG/NCS: low or unobtainable SNAPs with normal or reduced CMAPs amplitudes; slow CVs, distal denervation of EMG; irritability and myopathic MUAPs proximally in patients with superimposed toxic myopathy.
Amiodarone
It is an amphiphilic drug and leads to to drug-lipid complexes that are indigestible and which result in accumulation of autophagic vacuoles.
Symptoms of amiodarone-induced neuropathy usually begin between 18 - 30 months after starting the medication. It can cause paresthesia and pain in distal limbs. There is loss of large and small fiber sensory modalities and distal weakness in a length-dependent pattern; superimposed myopathy leading to proximal weakness. It can cause sensory ataxia. MSR are reduced or absent. ON is seen in some patients. Amiodarone can cause hypothyroidism, which contributes to proximal weakness. Patients with renal failure are prone to develop toxic neuromyopathy.
The most frequent neurotoxic findings were tremor, peripheral neuropathy, and ataxia . Five patients developed unusual neurotoxic manifestations: brainstem dysfunction characterized by downbeat nystagmus, hemisensory loss and ataxia, severe dyskinesia, jaw tremor, and proximal myopathy
It causes axonal degeneration and segmental demyelination (like CIDP) with myeloid inclusions in nerves and muscle fibers. Nerve pathology (sural) shows demyelination with axonal degeneration; lysosomal inclusions in Schwann cells.
Serum CK is elevated.
EMG/NCS: low or unobtainable SNAPs with normal or reduced CMAPs amplitudes; prolonged DML and F wave responses. Slow CVs, distal denervation of EMG; irritability and myopathic MUAPs proximally in patients with superimposed toxic myopathy.
Following cessation of drug, improvement usually follows a delay of many weeks, but satisfactory recovery occurs within 3-12 months in most cases, depending on initial severity. Recovery may be incomplete sometimes.
Colchicine inhibits polymerization of tubulin in microtubules and impairs axoplasmic flow. It causes numbness and paresthesia with loss of large fiber sensory modalities in a length-dependent fashion; superimposed myopathy may lead to proximal in addition to distal weakness. There is axonal degeneration; muscle fibers reveal axonal degeneration; and muscle fibers reveal vacuoles. EMG/NCS: low or unobtainable SNAPs with normal or reduced CMAPs amplitudes; slow CVs, distal denervation of EMG; irritability and myopathic MUAPs proximally in patients with superimposed toxic myopathy.
Podophyllin binds to microtubules and impairs axoplasmic flow. It causes sensory loss, tingling, muscle weakness, and diminished muscle stretch reflexes in a length-dependent pattern; autonomic neuropathy. Nerve histopathology shows axonal degeneration. EMG/NCS: low or unobtainable SNAPs with normal or reduced CMAP amplitudes.
Thalidomide mechanism is unknown. It causes numbness, tingling, burning pain, and weakness in a length-dependent pattern. There is axonal degeneration; degeneration of DRG. EMG/NCS: low or unobtainable SNAPs with normal or reduced CMAP amplitudes.
Disulfiram results in accumulation of neurofilaments and impaired axoplasmic flow. It causes numbness, tingling, and burning pain in a length-dependent pattern. It causes axonal degeneration and accumulation of neurofilaments in the axons. EMG/NCS: low amplitude or unobtainable SNAPs with normal or reduced CMAPs.
Dapsone mechanism is unknown. It produces a nonlength-dependent motor-predominant neuropathy or even a mononeuropathy multiplex that causes weakness in upper more than lower extremities, which is unusual for a toxic neuropathy.EMG/NCS: low amplitude or unobtainable CMAPs with normal or reduced SNAPs amplitudes.
Leflunomide mechanism is unknown. Leflunomide use is associated with peripheral neuropathy in some patients. This neuropathy is usually axonal, affecting multiple sensory or motor nerves of distal extremities. It causes paresthesia and numbness in a length-dependent pattern. EMG/NCS: low amplitudes or unobtainable SNAPs with normal or reduced CMAP amplitudes. Patients who stopped leflunomide use within 30 days of symptom onset were more likely to have improvement of symptoms or complete recovery than patients who continued to use the drug for longer periods.
Nitrofurantoin mechanism is unknown. It causes numbness, painful paresthesia, and severe weakness that may resemble GBS. There is axonal degeneration; degeneration of DRG and AHC. EMG/NCS: low amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes. It may present with a wide spectrum of manifestations, more commonly large-fiber sensorimotor neuropathy and smallfiber neuropathy. It can also cause non–length-dependent neuropathy and ganglionopathy is rarely described. In some cases the neuropathy is not reversible.
Pyridoxine (vitamin B6) mechanism is unknown. Severe sensory neuropathy can be caused by taking 2 - 6 gms of pyridoxine daily for 2 to 40 months. Patients show profound loss of most sensory modalities and almost all improve within 2-3 years when pyridoxine is stopped. Vitamin B6 in high doses is probably toxic to the dorsal root ganglia. It causes dysesthesia and sensory ataxia; impaired large fiber sensory modalities on examination. There is marked loss of sensory axons and cell bodies in DRG. EMG/NCS: reduced amplitudes or absent SNAPs.
Isoniazid inhibits pyridoxal phosphokinase leading to pyridoxine deficiency. It causes dysesthesia and sensory ataxia; impaired large fiber sensory modalities on examination. There is marked loss of sensory axons and cell bodies in DRG and degeneration of dorsal columns. EMG/NCS: reduced amplitudes or absent SNAPs and to a lesser extent CMAPs.
Ethambutol mechanism is unknown. It can cause numbness with loss of large fiber modalities on exam. EMG/NCS: reduced amplitudes or absent SNAPs.
Statins can cause neuropathy in less than 1% of patients. but its potential toxicity must be recognized when no other etiologies can be found in patients referred for an idiopathic polyneuropathy evaluation.
Special body burden toxicity tests (blood, urine, breath, hair, fat biopsy) are of limited help in many situations and may be misleading, even following analysis by an experienced toxicologist.
One issue is that laboratory tests do not exist for the body burden of many neurotoxins.
Another is that many compounds are harmless until metabolized to other substances that are toxic.
A third is that, usually by the time the neurologist sees the patient, exposure is long since over; few genuine neurotoxins are retained for weeks.
In our experience, a heavy metal determination in the evaluation of nonspecific chronic peripheral neuropathies is an especially frequent problem. The yield is essentially zero unless there are clear exposure and accompanying features, such as systemic illness, as in association with arsenic and thallium exposure, or a postural tremor in association with elemental mercury exposures. Industrial and environmental exposures occur, but the settings are usually known, and unsuspected exposures are extraordinarily rare. The common exceptions are intentional suicidal or homicidal poisoning. Despite these facts, determination of heavy metal levels is a common last-resort diagnostic procedure in the peripheral neuropathy evaluation; this can be confusing when mild or moderate elevations are found and patients request chelation therapy. For example, many persons in the community have mildly elevated levels of total arsenic (inorganic and organic). Organic arsenic is a pentavalent form of As and is innocuous, whereas, inorganic arsenic is trivalent and is toxic. Organic arsenic is present in many types of seafood and is harmless; the determination of potentially inorganic arsenic is expensive and only available in special laboratories. Exposure level assessments, except in obvious high-level instances, are an especially difficult issue, are beyond the scope of most neurologic investigations, and are best left to industrial hygienists and clinical toxicologists. Unfortunately, a neurologist’s ability to establish a neurotoxic cause of a particular problem may be limited by the absence of a definite measure of exposure. As previously stated, many individuals have chronic low-level contact with potentially neurotoxic substances at work or in the environment and may display increased body burdens of uncertain significance. Prominent examples include welders with elevated blood manganese levels, cigarette-smoking truck drivers with raised carbon monoxide levels, and solvent workers with elevated urinary toluene metabolites. This is an especially difficult issue when such persons develop a naturally occurring neurologic disease with similar manifestations, eg, Parkinson's disease in welders, multiple sclerosis workers with solvents. The consequences of chronic or acute low-level exposures have been clouded by flawed epidemiologic studies of some agents. Examples include the Gulf War syndrome/organophosphates, multiple sclerosis-like syndrome/dental amalgams, dysimmune neuropathy/silicone breast implants, painters encephalopathy/organic solvents, and peripheral neuropathy/dioxin. In sum, simply confirming exposure does not ensure that the toxin produced an adverse effect.
Heavy Metals: Arsenic, cadmium, mercury, lead, thallium, hexacarbon, N-hexane, methy-butyl ketone
Hexacarbons are water-insoluble industrial organic solvents, which also are present in some glues. Exposure through inhalation or skin absorption can lead to sensorimotor polyneuropathy primarily characterized by axon loss, although partial demyelinating conduction block has been reported. Nerve biopsy reveals loss of myelinated and giant axons filled with 10-nm filaments.
Organophosphates: Tricresyl phosphate.
Miscellaneous: Acrylamide, Bukthorn toxin, carbon disulfide, ciguatera toxin, diethyl glycol, ethylene oxide, ethylene glycol, hexachlorophane, methyl bormide, puffer fish toxin.
Metal chemistry: Arsenic is a naturally occurring ubiquitous element that is odorless, colorless, and nearly tasteless. Inorganic arsenic exists in a trivalent form called arsenite and in a pentavalent form called arsenate. Arsenic in food, particularly seafood, occurs predominantly as nontoxic organic compounds. Arsine is a toxic, colorless, nonirritating gas that evolves from arsenic-containing metal alloys exposed to acidic conditions during smelting of various ores. Arsenic is absorbed by the oral and inhalational routes. The latter route is responsible for toxicity due to occupational exposure. Arsenic is rapidly cleared from the blood. Inorganic arsenic is methylated in the liver to less toxic forms, which are excreted in the urine. Blood levels may become unmeasurable while urine levels remain elevated a few weeks after exposure cessation. Arsenic body burden is mainly found in the skin, hair, nails, bone, and teeth. Only a small amount of arsenic crosses the bloodbrain barrier. The primary mechanism of arsenic toxicity is related to sulfhydryl binding and disruption of protein structure and enzyme activity. An additional mechanism is replacement of phosphate molecules in “high-energy” compounds.
Sources of toxicity: Arsenic toxicity is common in Bangladesh and West Bengal since the majority of the rural population relies on ground water for daily use. Arsenic from natural geologic sources leaches into aquifers. Deep wells that tap groundwater contaminated with arsenic provide a source for chronic exposure. The major man-made sources of arsenic include nonferrous metal smelting, mining, abrasive blasting, pesticide manufacturing, combustion of coal, and burning of agricultural wastes. Burning of chromated copper arsenate-treated wood in fireplaces or wood stoves can be a source of arsenic toxicity. Arsenic is used in the manufacture of semiconductors, light-emitting diodes, transistors, lasers, computer microchips, and microwave circuits. It is also used in the glass and ceramic industry and in the manufacture of pigments. Arsenic is a constituent of some herbal medicines. In the past, trivalent forms of arsenic were commonly used for medicinal purposes.
Agricultural use of arsenic, such as its use in insecticides, pesticides, fungicides, herbicides, rodenticides, ant poisons, and fertilizers, has declined. The incidence of accidental, homicidal, and suicidal arsenic poisoning has greatly decreased. Arsenic trioxide used to be a common cause of poisoning. It now has use in the management of acute promyelocytic leukemia. The trivalent organic arsenic melarsoprol is used in the management of the meningoencephalitic phase of human African trypanosomiasis due to trypanosoma brucei rhodesiense.
Clinical features:
Acute arsenic toxicity. The neurotoxic effects of arsenic differ, depending on whether or not patients are subjected to an acute massive exposure or a chronic, low-level exposure.
A gastrointestinal illness is often the presenting symptom of acute arsenic poisoning. Colicky abdominal pain, profuse diarrhea, nausea, vomiting. It may mimic an acute abdominal emergency. Excessive salivation occurs and may be the presenting complaint in the absence of other gastrointestinal symptoms. The voluminous watery stools are described as “choleroid diarrhoea”. In cholera the stools are described as “rice water”, but in acute arsenic poisoning, because of blood in the gastrointestinal tract, the term“bloody rice water” diarrhoea is used. The cause of death is massive fluid loss due to secretion from the gastrointestinal tract eventuating in severe dehydration, reduced circulating blood volume, and consequent circulatory collapse. On autopsy esophagitis, gastritis, and hepatic steatosis are reported.
The acute GI features may be seen along or followed by an encephalopathy, renal failure, pulmonary edema, cardiovascular instability, bone marrow suppression, hemolysis, skin rash, and rhabdomyolysis. Multiorgan failure may ensue. Patients may complain of a metallic taste and have a garlic odor to the breath. High-dose exposure can lead to a syndrome that can mimic AIDP. Neuropathy begins 5 to 10 days after exposure and progresses over weeks. The PN may be delayed in onset by days to weeks and may progress for up to 6 weeks postexposure. The cranial nerves are typically not involved. Recovery is often incomplete. As with many toxic neuropathies, there may be a ‘‘coasting’’ effect, with continued progression of disease for a period of weeks after removal from exposure. Patients can develop flaccid areflexic quadriparesis, bifacial weakness, and even diaphragm paralysis, requiring ventilatory support.
Clinical manifestations can help distinguish arsenic toxicity from inflammatory demyelinating neuropathy, including a variety of systemic symptoms that may develop before the onset of neuropathy. Gastrointestinal disturbance with abdominal pain and vomiting, tachycardia, and hypotension are common, although these symptoms also may be seen in AIDP. Nonspecific systemic manifestations may follow, including hepatomegaly, renal failure, anemia, and cardiomyopathy, which are atypical for AIDP. Other systemic features are more specific to arsenic toxicity, such as brownish desquamation of the hands and feet (arsenical dermatitis) and Mees’ lines on fingernails and toenails. Unfortunately, the skin and nail changes may not appear until a month or more after isolated ingestion of arsenic, by which time the diagnosis rarely is still in question. If an initial EMG is performed within days, decreased motor unit recruitment may be the only finding. Over the first few weeks, EMG may show motor greater than sensory neuropathy with reduced amplitudes, borderline–low conduction velocities, prolonged F waves, and even partial conduction block in several motor nerves. The nerve conduction studies even may fulfill criteria for the diagnosis of an acquired demyelinating neuropathy. Cases even are reported in which the sural sensory response is normal, but the median sensory response is absent, a finding often found in AIDP . Follow-up studies are more consistent with a typical dying-back axonopathy, with absent sensory and motor responses and denervation/reinnervation changes on needle EMG.
The classic triad of acute arsine gas exposure includes abdominal pain, hematuria, and jaundice.
Clinical features manifest in virtually all body systems.
Acute arsenic poisoning:
Prominent features are nausea, vomiting, colicky abdominal pain, profuse watery diarrhea, and excessive salivation.
Other features are acute psychosis, a diffuse skin rash, toxic cardiomyopathy, and seizures.
Hematological abnormalities occur and renal failure, respiratory failure, and pulmonary edema are common.
Neurological manifestations include peripheral neuropathy or encephalopathy.
Urinary arsenic concentration is the best indicator of recent poisoning (1–2 days).
Chronic arsenic toxicity is a multisystem disease. The typical presentation is a gradual-onset sensorimotor PN with delayed onset of skin changes (hyperpigmentation, palmar and plantar hyperkeratosis, skin malignancies), alopecia, and Mees lines. Mees lines are transverse white lines across nails that represent growth disruption, not arsenic deposition. The delayed onset and limited specificity limits their diagnostic utility. Other manifestations of chronic toxicity include malaise, anorexia, weight loss, metallic taste, bone marrow suppression, pulmonary disease, diarrhea, constipation, hepatomegaly, portal hypertension, and possibly cognitive impairment. “Blackfoot disease” is a peripheral vascular disease that is characterized by foot gangrene. It is endemic in Taiwan and is probably due to arsenic-contaminated well water. Raynaud phenomenon and acrocyanosis also may occur in this disease. Inorganic arsenic is a human carcinogen. Arsenic trioxide, when used in the management of acute promyelocytic leukemia, may cause cardiac arrhythmias, skin rash, hyperglycemia, or PN. The recognized neurotoxicity of melarsoprol includes a reactive encephalopathy, a GBS-like neuropathy, and MRI evidence of a multifocal inflammatory illness.
Chronic arsenic poisoning:
The clinical features manifest in virtually all body systems.
Absorbed arsenic accumulates in the liver, kidneys, heart and lungs, with smaller amounts in the muscles, nervous system, gastrointestinal tract, spleen, and lungs.
Arsenic is deposited in the keratin-rich tissues: nails, hair, and skin.
Mee’s lines occur in the fingernails and toenails.
The most serious consequence is malignant change in almost all organs of the body.
Dermatological changes are common, such as hyperpigmentation and both palmar and solar keratoses.
There is increased risk of cardiovascular disease, peripheral vascular disease, respiratory disease, diabetes mellitus, and neutropenia.
Effective treatment of chronic arsenic toxicity is not yet established.
Investigations: Laboratory evaluation in arsenic toxicity may show anemia, pancytopenia, basophilic stippling, elevated hepatic transaminases, and evidence of renal insufficiency. The radiopaque metal can be visualized as patchy infiltrates on abdominal radiographs. Blood arsenic levels are of limited utility because serum arsenic is cleared within hours. Hence, urinary arsenic excretion rates are more useful than blood arsenic levels in acute intoxication. Nerve conduction studies in the initial stages show evidence of a demyelinating polyradiculoneuropathy. Later the findings are consistent with a distal axonopathy.
Management: In high-risk areas, levels of arsenic in water sources should be tested and maintained within the acceptable range. Appropriate precautions and restriction are required with chromated copper arsenate-treated wood. Standard decontamination procedures have a limited role. Hemodialysis may have a role for enhancing elimination in the presence of renal failure. Alkalinization of the urine may prevent the deposition of red cell breakdown products in the renal tubules. The suggested indications for chelation include a severely symptomatic patient after confirmed acute ingestion, symptomatic patients with urinary arsenic greater than 50 g/L, and asymptomatic patients with urinary arsenic greater than 200 g/L. The utility of chelation in preventing progression of acute arsenic neuropathy is unknown. Patients with significant gastrointestinal distress should be started on a parenteral chelator such as British anti-Lewisite (BAL) therapy or dimercaptopropanesulfonic acid (DMPS). Subsequently, an oral chelator such as DMPS, 2,3-dimercaptosuccinic acid (DMSA), or penicillamine may be used. Neuropathy may be prevented if therapy is instituted within hours of exposure. DMPS has also been reported to cause improvement in PN associated with chronic arsenic poisoning. BAL is not effective in treating established neuropathy and may increase the brain arsenic content. DMSA does enhance elimination of arsenic after acute poisoning but may not be beneficial in chronic arsenic toxicity. With arsine gas exposure, chelating agents are ineffective. Exchange transfusion and forced alkaline diuresis may be required for arsine poisoning.
Laboratory testing can aid in the diagnosis of arsenic poisoning in acute and chronic settings. Urine arsenic levels greater than 25 mg in a 24-hour specimen generally are considered abnormal, although levels may be elevated falsely by the ingestion of seafood, in particular bottom-feeding finfish. Small amounts of arsenic bind to keratin in growing tissues, allowing diagnosis to be made by measuring levels in hair and nails. This is useful particularly in the setting of chronic or low-level exposure or for detecting a remote exposure that has since ceased. Blood arsenic levels are not helpful, because serum arsenic is cleared within 2 to 4 hours; ingestion of seafood results in elevated urine arsenic due to the nontoxic organic form. Within hours of seafood ingestion total urinary arsenic concentration may be in the range of 100 g/L to 10,000 g/L. Seafood should be avoided for 3 to 4 days prior to a urine arsenic determination.
Chelation with penicillamine or dimercaprol should be started as soon as possible after exposure. The usefulness of chelation in preventing progression of acute arsenical neuropathy is unknown, however.
Zinc is an essential trace element that is required in daily quantities of 5.5 to 9.5 mg for men, and 4 to 7 mg for women.
Axonopathy: Almitrine, amiodarone, amitryptiline, Ara-C, bortezomib, carbimide, chloramphenicol, chloroquine, cimetidine, clioquinol, colchicine, clofibrate, cyanate, cyclosporine, didanosine (ddI), dichloroacetate, disopyramide, disulfiram, ifosfamide, enalapril, ethambutol, ethionamide, etretinate, fialuridine (FIAU), fluoroquinolone, hydralazine, gold, glutethimide, isoniazid, lamivudine (3TC), lansprazole, leflunomide. linezolid, lithium, mefloquine, mercury, methaqualone, metronidazole, misonidazole, nitrofurantoin, nitrous oxide, paclitaxel, phenelzine, phenytoin, podophyllin, propafenone, sulfapyridine, sulfadiazine, statins, stavudine (d4T), suramin, tacrolimus, thalidomide, tumor necrosis factor-alpha antagonists, vancomycin, vincristine, zalcitabine (ddC).
AHC: Dapsone
DRG: Cisplatin, carboplatin, ifofosfamide, etoposide (VK-16), oxaliplatin, pyridoxine.
Schwann Cell: Allopurinol, amiodarone, Ara-C, gentamicin, griseofulvin, indomethacin, L-tryptophan, perhexiline, streptokinase, suramin, tacrolimus, TNF-apha antagonist, L-tryptophan, zimeldine.