The clinical manifestations of arsenic exposure depend on the level of exposure. High-dose exposure results in rapid onset of severe gastrointestinal disturbance (eg, abdominal pain, vomiting, and diarrhea), as well as tachycardia, hypotension, and vasomotor collapse with possible death (Ghariani et al 1991; Berger and Schaumburg 1996). In addition, CNS dysfunction may occur, which can be transient (eg, organic psychosis, somnolence, or stupor) (O'Shaughnessy and Kraft 1976), or prolonged (eg, behavioral and cognitive problems). If the subject survives acute high-level exposure, the neuropathy begins to manifest within weeks and may continue to worsen for a period of weeks after removal from exposure (coasting). Sensory symptoms including painful paresthesias and numbness predominate. Burning, aching, and tingling are positive sensory phenomena that occur first in the toes and feet, but later in the fingers. Similarly, weakness follows a length-dependent pattern, starting with the feet and later involving the hands. With high-dose exposure or inadequate treatment, the weakness may progress to involve the respiratory muscles and mimic Guillain-Barré syndrome. The deep tendon reflexes are depressed or absent early in the process. In addition to nervous system manifestations, high-dose toxicity often causes bone marrow suppression and skin changes.
Chronic exposure to lower levels of arsenic results in dermatologic manifestations prior to overt clinical neuropathy. The patient may complain about symptoms of anorexia, malaise, generalized weakness, and vomiting. This is followed by hyperpigmentation of the skin, white transverse lines in the nails (Mee lines), hyperkeratosis, and irritation of the mucous membranes. Although asymptomatic at this point, neuropathy may be detected by careful examination and electrophysiologic testing. Clinical neuropathy characterized by burning and numbness of the feet and later the hands results from continued exposure. This involves both small and large fiber sensory disturbance with resultant difficulties with proprioception, in addition to the dysesthesias. Weakness tends to be mild and limited to the most distal muscles. Recovery is related to the severity of the neuropathy at the onset of treatment. Mild cases recover completely, whereas more serve cases may have significant residua.
The large group of arsenic toxicity patients identified in India by Mukherjee and colleagues and Rahman and colleagues were divided into those that had chronic exposure and those that had subacute evolution of toxicity (Rahman et al 2001; Mukherjee et al 2003). Those with subacute exposure had a much higher incidence of neuropathy (33 of 38 versus 154 of 413). The neuropathy manifestations were similar in both groups with painful paresthesias and other sensory complaints occurring more commonly than motor symptoms or signs. The prognosis of patients in this large cohort conforms to previous experience as described above. The most recent report of a large-group exposure to arsenic involved workers in a copper smelting facility in China (Xu et al 2008). In that series, 45 of 104 workers developed symptoms suggestive of peripheral neuropathy approximately 3 weeks after a subacute (3- to 5-day) exposure to arsenic, and 25 of those 45 workers had abnormal sensory and motor nerve conduction velocity.