IntroductionArsenic is a semi-metallic poison known since ancient times. Geber, an Arab alchemist of eighth century produced arsenious oxide, from realgar which is a naturally occurring ore found in lead and iron mining, and thus one of the most cruel, deadly and widely administered poisons during the medieval history was made available to the humanity. In the modern times, the nature of arsenic threat has changed. Instead of an acute poison used as insecticide, rodenticide or homicidal/suicidal purpose, it has become a chronic poison mobilized by natural or anthropogenic reasons.

Clinical description
Acute ingestion of toxic amounts of inorganic arsenic typically causes severe gastrointestinal signs and symptoms (e.g., vomiting, abdominal pain, and diarrhea). These signs and symptoms might rapidly lead to dehydration and shock. Different clinical manifestations might follow, including dysrhythmias (prolonged QT, T-wave changes), altered mental status, and multisystem organ failure that might ultimately result in death.

Laboratory criteria for diagnosis
• Biologic: A case in which elevated urinary arsenic levels (>50 µg/L for a spot or >50 µg total for a 24-hour urine) exist, as determined by commercial laboratory tests. Speciation is required in all cases where total urine arsenic is elevated to differentiate the amount of organic and inorganic arsenic.
-OR-
• Environmental: Detection of arsenic in environmental samples above typical background levels, as determined by NIOSH or FDA.

Case classification• Suspected: A case in which a potentially exposed person is being evaluated by health-care workers or public health officials for poisoning by a particular chemical agent, but no specific credible threat exists.
• Probable: A clinically compatible case in which a high index of suspicion (credible threat or patient history regarding location and time) exists for arsenic exposure, or an epidemiologic link exists between this case and a laboratory-confirmed case.
• Confirmed: A clinically compatible case in which laboratory tests have confirmed exposure. The case can be confirmed if laboratory testing was not performed because either a predominant amount of clinical and nonspecific laboratory evidence of a particular chemical was present or a 100% certainty of the etiology of the agent is known.

PresentationAcute poisoning:
-symptoms may develop in minutes or hours
-usually GI first with nausea, vomiting, abdominal pain and diarrhea
-garlic odor of breath and stool in severe poisoning
-develop dehydration, hypotension, irregular pulse and cardiac instability (even shock, ARDS, death)
-Some cases, acute encephalopathy over days, with delirium, coma, and seizures; renal injury with proteinuria, hematuria, and ATN.
- If survive, usually develop hepatitis and pancytopenia (usually reversible) in a week;
sensorimotor peripheral neuropathy at 1-3 weeks later (occasional partial recovery possible)
-Other symptoms: patchy alopecia, diffuse pruritic macular rash, herpetic-like ulcers in mouth, dry hacking cough, Mees lines
Subacute poisoning:
-persistent gastroenteritis and mild hypotension
-metallic taste and irritated mucous membranes that mimic pharyngitis
Chronic poisoning:
-peripheral neurologic and skin symptoms more prominent than GI
-skin: hyper/hypo pigmentation (may be early), hyperkeratosis and scaling particularly
palms and soles, eczematous lesions, skin carcinomas, peripheral vascular disease with gangrene
-neuro: symmetric sensorimotor polyneuropathy with sensory first and more prominent
(starting vibratory sense; progressive symptoms in stocking/glove distribution with decreased pain, touch, temperature, symmetrical weakness, decreased DTRs
-cancer: skin, bladder, lung, kidney, nasal, liver, and prostate
-increased risk of HTN
-liver: hepatic angiosarcoma, hepatomegaly, noncirrhotic portal fibrosis
-endocrine: association with developing DM.

EvaluationAcute exposure: abdominal X-rays may show radiopaque material, measurement of urine arsenic levels (preferable to blood which is cleared quickly) which are usually in the thousands of micrograms/L (fish or shellfish intake <48hrs may elevate levels of nontoxic “fish arsenic”, can speciate total, organic, and inorganic)
Chronic exposure: 24hr or spot urine (after pt abstains from fish/shellfish 48-72hrs); hair and nail analyses not standardized and difficult to remove exogenous arsenic in industrial exposures; cbc, renal and liver function tests.

Treatment
Acute: First eliminate exposure – decontaminate skin, hair, and clothes. Activated charcoal (efficacy debated), monitor fluid/electrolyte balance, avoid agents that prolong Qt, consider chelation therapy with dimercaprol or succimer
Chronic: may benefit from succimer.

Teaching points1. In cases where etiology of polyneuropathy is unclear, EMG testing should be considered earlier rather than later in workup. It can really help to narrow differential.
2. Arsenic testing: clears from blood quickly, so urine preferred and patient should abstain at least 48hrs from shellfish and fish prior to testing.
3. Chronic arsenic poisoning not only give neurologic and skin effects, but also increases risk of multiple malignancies, HTN, and DM.