Arsenic is a heavy metal that exists in three metallic forms, alpha or yellow, beta or black and gamma or grey. It also exists in compounds that may be organic or inorganic. Poisoning can occur by ingestion, inhalation and dermal absorption. Inorganic compounds are much more toxic than organic compounds. Elemental arsenic is least toxic. Trivalent arsenic is well absorbed through the skin and is 60 times more toxic than pentavalent arsenic, which is well absorbed by the gut.¹ Arsine gas is highly toxic.

Toxicity is due to arsenic's effect on many cell enzymes, which affect metabolism and DNA repair. Arsenic is excreted in urine, but can also accumulate in many body tissues.²

Arsenic has been used in medicines, as a pigment, a pesticide, and as a weapon of murder. It shares many toxic features with the other heavy metals like mercury and lead. It is used in the production of glass and semiconductors. It is found in some water supplies and seafood, and is used in various industries.

Epidemiology

In Victorian times arsenic was commonly used for murder but nowadays it is used much less as it is more difficult to acquire. Health and safety at work have also improved so that, in this country, both acute and chronic arsenic poisoning are rare.

Contamination of water supplies has occurred in parts of:³

• Bangladesh and West Bengal, affecting millions of people.
• Chile (the Antofagasta region), Argentina, Mexico and the USA.
• China, Taiwan, Thailand.

Aetiology^2,4

Sources of arsenic poisoning include:

• Contaminated drinking water (as above).
• Some ayurvedic medicines⁵ and Chinese herbal medicines.
• Pesticides.
• Herbicides.
• Fungicides.
• Wood preservatives.
• Ceramic enamels.
• Paints.
• Tobacco (there may be as much as 6 mcg per pack).
• Burning of fossil fuels as arsenic is a contaminant.
• In the USA, illicit whiskey ('moonshine').⁶

Occupational exposure can occur in:

• The smelting industry (arsenic is a byproduct of ores containing lead, gold, zinc, cobalt and nickel).
• The microelectronics industry (as gallium arsenide).
• Coal power plants.
• Manufacture of glass and fireworks.
• Use of pesticides.
• Contact with wood treated with arsenic as a preservative.

Note that organic arsenics found in fish and seafood are non-toxic and not a cause of arsenic poisoning. Similarly, the long-term exposure with the cutting and burning of wood preserved with copper chrome arsenate leads to elevated blood levels but no signs or symptoms of toxicity.

Presentation

History

• Arsenic exposure is usually occupational or environmental, but can result from deliberate poisoning.
• Exposure to arsine gas is usually the result of an industrial accident.
• Take a work and travel history when a patient presents with painful peripheral neuropathy.
• Other history: hobbies, unusual forms of alcohol or diet supplements, herbal medicines.
• Many organ systems are involved.

Features of acute arsenic poisoning¹

Overview of acute poisoning features

Symptoms usually start within 30 minutes to 2 hours. Acute arsenic ingestion is typically followed by a severe gastroenteritis, garlic odour and hypersalivation. There is a characteristic sequence of multi-organ failure, with: neurological symptoms (within hours) and cardiac features, succeeded by adult respiratory distress syndrome and renal/liver dysfunction. Marrow suppression develops after a few days to weeks in survivors, as does alopecia and an ascending motor neuropathy.

Details of acute poisoning features

• Garlic odour - often present in breath and body tissues.
• Gastrointestinal (GI):
  • Hypersalivation, abdominal pain, vomiting, diarrhoea leading to hypovolaemic shock.
  • Trivalent arsenic is corrosive - may cause oral burns, dysphagia and GI bleeding.
• Cardiovascular:
  • Myocardial depression.
  • Dehydration, hypovolaemia or shock.
  • ECG changes including ST segment changes, prolonged QT interval, ventricular tachycardia, torsades de pointes and ventricular fibrillation.
  • Gangrene of extremities.
• Respiratory:
  • Pulmonary oedema, adult respiratory distress syndrome and acute respiratory failure.
  • Inhaled arsenic causes irritation, bronchospasm and pulmonary oedema.
• Renal and hepatic:
  • Haematuria or haemoglobinuria (from acute haemolysis), proteinuria, acute tubular necrosis with acute renal failure.
  • Jaundice, hepatomegaly, pancreatitis.
• Neurological:
  • CNS depression, encephalopathy and coma.
  • Seizures.
• Haematological:
  • Acute haemolysis.
  • Bone marrow suppression.
  • Basophilic stippling and rouleaux formation may be seen on a blood film.
• Skin: rashes.

Features of chronic arsenic poisoning^1,2,3,7

The main clinical features and possible complications are:

• Skin lesions:
  • These typically start about ten years after first exposure.
  • Keratoses on the palms and soles are characteristic.
  • Mees' lines (transverse white lines on nails).⁵
  • Hyperpigmentation (especially on the arms and upper chest) - diffuse dark areas or 'raindrop' pigmentation.
  • Also, exfoliative dermatitis, alopecia, conjunctivitis, corneal ulceration.
• GI:
  • Anorexia, weight loss, abdominal pain, diarrhoea.
  • Jaundice, hepatomegaly.
• Cardiac/respiratory:
  • Myocarditis, pericarditis.
  • Hypertension - increased risk.
  • Restrictive or obstructive lung disease.
• Haematological: pancytopenia, aplastic anaemia.
• Neurological:
  • Peripheral neuropathy (sensory and motor at 1-3 weeks).
  • Muscle fasciculation and wasting.
  • Ataxia.
• Diabetes - increased risk.
• Cancer - increased risk of cancers: skin, lung, liver, bladder, kidney, larynx and lymphoid system.

Differential diagnosis

Other forms of poisoning, e.g. lead, mercury; botulism, gastroenteritis and haemolytic uraemic syndrome. The skin lesions look like other forms of dermatitis.

Investigations

Acute poisoning¹

• Monitoring - for least four hours after suspected ingestion: pulse, blood pressure, respiratory rate, oxygen saturation and ECG, urine output.
• Haematology, biochemistry and arterial blood gases - as for any acutely ill patient.
• Urinalysis.
• ECG.
• Arsenic levels in blood and urine (see box below for normal levels).
• CXR and plain abdominal X-ray (inorganic arsenic compounds are radio-opaque).

Chronic arsenic poisoning

• Urinary concentrations are useful in chronic exposure.¹
• Hair samples (as above).
• Arsenic levels in drinking water (high drinking water levels in conjunction with relevant clinical features are useful for diagnosis in some settings).
• Investigation and screening for complications may be appropriate (e.g. look for diabetes, hypertension).

Management

Management of chronic arsenic poisoning^3,10

• Provide arsenic-free drinking water, to reduce the risk of further disease developing. Anecdotal evidence suggests that mild-moderate keratoses may improve with cessation of exposure.
• Chelation therapy may have a role, but its effectiveness is uncertain.^11,12 Also, it is of no use if exposure to arsenic continues.
• Micronutrients and antioxidants may be beneficial, especially in undernourished populations.¹¹ It is recommended that all patients with skin lesions be given multivitamins.
• Certain plant compounds may help to remove arsenic from tissues.^11,13
• Skin care for keratoses and any associated bacterial or fungal infections.
• Screen and treat for complications, e.g. diabetes, hypertension.
• Other household members:
  • Check other members of the family, as they may also have been exposed.
  • Pregnancy and breast-feeding: arsenic is probably transferred to the baby via the placenta and breast milk.²

Staging

Arsenic poisoning has been classified into 4 stages, 7 grades and 20 subgrades¹⁴ but this is not common practice.

Prognosis^2,10

• The prognosis varies with the amount and rate of arsenic ingestion.
• Effects and complications can occur at different times after exposure - from days to years later.

Prevention

• Test all groundwater sources of drinking water for arsenic.
• Provision of uncontaminated water for all is essential, but not yet achieved.¹⁵Some plants have the ability to remove arsenic from the environment.¹⁶

History and politics

Historically, arsenic was used medicinally;² prolonged use led to chronic skin effects. This was noted by Hutchinson in 1888. Arsenic in poison gas ('Lewisite') was used in World War I. The agent used to treat it, dimercaprol, was known as British anti-Lewisite (BAL).⁸

Bangladesh was proud that 97% of its population had access to clean water from wells. This was free of the bacterial contamination that caused so much disease, but it later transpired that much of the water was high in arsenic. Millions of people in Bangladesh, West Bengal and possibly other areas, are at risk of arsenic poisoning.¹⁷ According to some estimates, arsenic in drinking water will cause 5 million deaths in Bangladesh. The World Health Organization (WHO) has called it the "largest mass poisoning of a population in history" and a public health emergency.³ Chronic arsenic poisoning is likely to become an international health issue and requires research and awareness worldwide.

Document references

1. Toxbase; (Registration is free for doctors who are employed by an NHS practice)
2. Ratnaike RN; Acute and chronic arsenic toxicity. Postgrad Med J. 2003 Jul;79(933):391-6. [abstract]
3. Smith AH, Lingas EO, Rahman M; Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ. 2000;78(9):1093-103. [abstract]
4. Marcus S; Arsenic Toxicity in Emergency Medicine, Medscape, Sep 2010
5. Anand, K and Varadarjalu, R. Photograph showing Mees lines. In: Minerva. British Medical Journal 2004: 329;1112 (6 November).
6. Gerhardt RE, Crecelius EA, Hudson JB; Moonshine-related arsenic poisoning.; Arch Intern Med. 1980 Feb;140(2):211-3. [abstract]
7. Chronic arsenic poisoning, DermNet NZ; Information and pictures on symptoms of chronic poisoning
8. Dyro, FM; Neurological Manifestations of Arsenic Intoxication, Medscape, Jan 2010
9. Murray L, Daly F, Little M & Cadogan M. Toxicology Handbook 2nd Ed. Churchill Livingstone 2011
10. Rahman MM, Chowdhury UK, Mukherjee SC, et al; Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary. J Toxicol Clin Toxicol. 2001;39(7):683-700. [abstract]
11. Kalia K, Flora SJ; Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning. J Occup Health. 2005 Jan;47(1):1-21. [abstract]
12. Guha Mazumder DN, De BK, Santra A, et al; Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water. J Toxicol Clin Toxicol. 2001;39(7):665-74. [abstract]
13. Misbahuddin M, Islam AZ, Khandker S, et al; Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: a randomized placebo-controlled study. Clin Toxicol (Phila). 2006;44(2):135-41. [abstract]
14. Saha KC; Diagnosis of arsenicosis.; J Environ Sci Health A Tox Hazard Subst Environ Eng. 2003 [abstract]
15. sos-arsenic.net; A campaigning website about arsenic poisoning in India and Bangladesh.
16. Alkorta I, Hernandez-Allica J, Garbisu C; Plants against the global epidemic of arsenic poisoning.; Environ Int. 2004 Sep;30(7):949-51. [abstract]
17. Kumar S; News Roundup BMJ. Millions more at risk of arsenic poisoning than previously thought. BMJ 2003;326:466 ( 1 March )

Internet and further reading

• Smith AH, Lingas EO, Rahman M; Contamination of drinking-water by arsenic in Bangladesh: a public health emergency, World Health Organization
• Murray L, Daly F, Little M & Cadogan M. Toxicology Handbook 2nd Ed. Churchill Livingstone 2011

Acknowledgements