What are the diagnostic steps for chronic arsenic exposure?

Diagnosing Chronic Arsenic Exposure

Diagnose chronic arsenic exposure through 24-hour urine arsenic testing combined with clinical assessment of characteristic skin changes (melanosis and hyperkeratosis), while critically distinguishing between toxic inorganic arsenic and benign organic arsenic from seafood consumption. 1, 2, 3

Laboratory Testing Approach

Primary Diagnostic Test

• 24-hour urine collection is the gold standard for diagnosing chronic arsenic exposure, as it reflects ongoing exposure better than blood levels, which are transitory 3, 4
• Spot urine samples are acceptable alternatives when 24-hour collection is impractical 3
• Testing must be performed by OSHA-designated laboratories using inductively coupled plasma-mass spectrometry (ICP-MS) 3

Critical Interpretation Caveat: The Seafood Problem

• Seafood consumption can dramatically elevate urinary arsenic levels without any clinical toxicity, creating a major diagnostic pitfall 1, 2
• Organic arsenic compounds (arsenobetaine, arsenosugars, arsenolipids) from seafood are relatively non-toxic and rapidly excreted unchanged in urine within 24-48 hours 5
• Do not dismiss elevated urinary arsenic in patients reporting high seafood consumption, as organic arsenic can mask concurrent toxic inorganic arsenic exposure 2
• Instruct patients to avoid all seafood for 3-5 days before urine collection to eliminate this confounding factor 5

Supplementary Biomarkers

• Hair and nail arsenic analysis reflects past exposure (weeks to months) rather than current levels, useful for confirming chronic exposure history 3, 6
• Hair analysis has significant limitations due to external contamination that cannot be reliably distinguished from ingested arsenic 4
• Bone arsenic load measurement, when available, provides the most accurate assessment of total body burden in chronic exposure 7

Clinical Diagnostic Criteria

Essential Cutaneous Manifestations

Skin changes are the most sensitive and earliest indicators of chronic arsenic toxicity and can establish diagnosis even without laboratory confirmation 6, 8:

• Melanosis: Diffuse hyperpigmentation with characteristic "raindrop" pattern of hypopigmented macules on hyperpigmented background, typically on trunk and extremities 9, 6
• Hyperkeratosis: Palmar and plantar keratoses appearing as punctate, corn-like lesions on pressure points 9, 6, 8
• Skin lesions may appear at exposure levels as low as 0.005-0.01 mg/L arsenic in drinking water 8

Systemic Manifestations to Assess

• Gastrointestinal: Metallic taste, nausea, abdominal pain, diarrhea 9
• Neurological: Peripheral neuropathy (stocking-glove distribution), toxic encephalopathy 9, 8
• Hematologic: Anemia, bone marrow depression, pancytopenia 9
• Hepatic: Liver disease, noncirrhotic portal hypertension with esophageal varices 9
• Vascular: Raynaud's phenomenon, acrocyanosis, peripheral vascular disease ("blackfoot disease") 9, 8
• Mee's lines: Transverse white bands on fingernails appearing 4-6 weeks after exposure 9

Exposure Source Investigation

Water Testing

• Test drinking water sources in high-risk geographic areas including Southwest, New England, upper Midwest, and Western United States where groundwater naturally contains elevated arsenic 2
• Water arsenic levels consumed in the last 6 months are diagnostically valuable 6
• The WHO guideline for safe drinking water is 10 μg/L (0.01 mg/L) 8

Occupational and Environmental History

• Document exposure to chromated copper arsenate (CCA)-treated wood, pesticides, herbicides, or industrial processes 9
• Assess for contaminated groundwater in endemic regions (Bangladesh, India, Pakistan, Taiwan) 9, 8

Diagnostic Algorithm

1. Obtain detailed exposure history focusing on water sources, occupation, and seafood consumption 1, 2
2. Perform thorough skin examination for melanosis and hyperkeratosis patterns 6, 8
3. Order 24-hour urine arsenic after 3-5 days of seafood avoidance 5, 3
4. Test drinking water source for arsenic concentration 2, 6
5. Consider hair/nail analysis for chronic exposure confirmation if urine results are equivocal 3, 6
6. Assess for systemic complications including peripheral neuropathy, liver disease, and vascular changes 9, 8

Long-Term Monitoring Considerations

• Patients with confirmed chronic arsenic exposure require lifelong surveillance for malignancies, particularly skin, lung, and bladder cancers 2, 8
• Skin cancer risk is elevated even years after exposure cessation 8
• Regular dermatologic examination is essential for early cancer detection 6