AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mercury has various forms and thousands of industrial uses; however, it is probably best known as the silver liquid in thermometers. Mercury is ubiquitous in nature, occurring as mercuric sulfide or cinnabar.

Mercury has 3 forms: (1) elemental mercury, (2) inorganic salts, and (3) organic compounds. Perhaps the most deadly form of mercury is methyl mercury. Only 2-10% of the ingested mercury is absorbed from the gut, and ingested elemental mercury is not absorbed at all; however, 90% of any methyl mercury ingested is absorbed into the bloodstream from the GI tract.

Organic mercury compounds, specifically methyl mercury, are concentrated in the food chain. Fish from contaminated waters are the most common culprits. Industrial mercury pollution is often in the inorganic form, but aquatic organisms and vegetation in waterways such as rivers, lakes, and bays convert it to deadly methyl mercury. Fish eat contaminated vegetation, and the mercury becomes biomagnified in the fish. Fish protein binds more than 90% of the consumed methyl mercury so tightly that even the most vigorous cooking methods (eg, deep-frying, boiling, baking, pan-frying) cannot remove it.

Methyl mercury poisoning, better known as Minamata disease, is one of the most devastating forms of mercury exposure. It is named for Minamata Bay, a body of water in Japan where, in the early 1950s, the fish contained high concentrations of methyl mercury from the polluted waste of a nearby industrial plant.¹ Local villagers ate the fish and began to exhibit signs of neurologic damage such as visual loss, extremity numbness, hearing loss, and ataxia. Babies exposed to the methyl mercury in utero were the most severely affected members of the village. Furthermore, because mercury was also discovered in the breast milk of the mothers, the babies' exposure continued after birth.

Pathophysiology

Organic forms, specifically methyl mercury, are the most toxic of the 3 classes of mercurials. The GI tract absorbs more than 90% of the methyl mercury ingested, which then enters the bloodstream. Because mercury binds to the body's ubiquitous sulfhydryl groups, toxicity involves multiple organ systems. Structural proteins, membranes, and enzymes are all disrupted.

Methyl mercury exerts its most devastating effect on the CNS by causing psychiatric disturbances, ataxia, visual loss, hearing loss, and neuropathy. Methyl mercury is lipophilic and readily crosses the blood-brain and placentofetal barriers. Neurologic damage in the form of diffuse and widespread neuronal atrophy is most severe in patients exposed in utero.

Necrosis of the proximal tubules is a common direct renal toxic effect. Unexplained renal abnormalities with neuropsychiatric disturbances should prompt the physician to consider Minamata disease or other forms of mercury poisoning.

Frequency

United States

Mercury poisoning is episodic and usually involves the inhalation of elemental mercury vapor or an exposure to inorganic mercuric salts; methyl mercury intoxication has been reported in the United States.

International

Worldwide, outbreaks of methyl mercury intoxication are sporadic. Minamata Bay in Japan was involved in the first and most famous epidemic but not the largest. In the early 1970s, one of the most severe mass poisonings in history occurred in Iraq when nearly 95,000 tons of seed grains treated with a methyl mercury–based fungicide were accidentally baked into bread for human consumption.² More than 6000 individuals were hospitalized, and hundreds died. Many were hospitalized for weeks before methyl mercury intoxication was correctly diagnosed.

Mercury mining areas in China have also contributed to cases of methyl mercury poisoning through the ingestion of rice grown in contaminated soil.³

Mortality/Morbidity

• Of the original 121 individuals from Minamata Bay who were affected (see Frequency), nearly one third died shortly after their initial presentation.¹
• Subsequent investigations over the last 3 decades resulted in the identification of more than 2000 additional patients who were affected by chronic sequelae of Minamata disease.¹
• Of the more than 6000 Iraqi patients (see Frequency), 459 died.²

Sex

Both sexes can be affected.

Age

Although Minamata disease can affect children of all ages, babies exposed in utero are most severely affected.

• Autopsy evidence reveals that brain atrophy is significantly worse in children than in adults.
• Exposure to mercury has been suggested to contribute to the development of autism in children.
• • Although the mechanism for this disorder has many hypotheses, no evidence has confirmed or disproved a causal relationship between mercury exposure and the development of autism. In fact, in one recent study, the discontinuation of thimerosal-containing vaccines in Denmark seemed to be followed by an increase in incidence of autism.⁴
  • Further studies are needed to elucidate a link, if any, between mercury exposure and autism development.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• If methyl mercury intoxication is suspected, inquire about the patient's diet, including the following:
• • Amount of fish consumed
  • Frequency of consumption
  • Types of fish consumed
  • Source of fish consumed
  • Source of water supply
• Also inquire about classic symptoms, including the following:  
• • Perioral and facial paresthesias
  • Extremity numbness
  • Dysarthria
  • Headache
  • Constriction of the visual fields
  • Difficulty in hearing
  • Memory loss
  • Problems with walking
• Methyl mercury exerts its most devastating effect on the CNS by causing the following:  
• • Psychiatric disturbances
  • Ataxia
  • Visual loss
  • Hearing loss
  • Neuropathy

Physical

• Clinical examination typically reveals the following:
• • Deficits in the visual field relative to confrontation
  • Ataxia
  • Tremor
  • Psychiatric disturbances such as anxiety and agitation
  • Seizures
• Respiratory distress and dermatitis can occur acutely.
• Neurotoxicity is the most damaging syndrome.
• Severe poisoning eventually causes the patient to lie in a mute semirigid posture that is broken only by episodes of crying or primitive reflexive movements.
• Unexplained renal abnormalities with neuropsychiatric disturbances should prompt the physician to consider Minamata disease or other forms of mercury poisoning.
• The most damaging effect of ingested inorganic mercury (eg, mercuric chloride) is caustic gastroenteritis.
• Ingested elemental mercury is considered nontoxic because of its poor absorption in the gut; it is most dangerous as a vapor because it can cause acute lung injury and respiratory failure.

Causes

• Classic methyl mercury intoxication occurs as the result of ingesting contaminated seafood, usually fish.
• • Organic mercury compounds, specifically methyl mercury, are concentrated in the food chain.
  • Fish from contaminated waters are the most common culprits.
  • Larger species, such as swordfish, shark, and large tuna, have higher concentrations of methyl mercury in their tissues.
• Other sources of mercury include batteries and thermometers.
• • Mercury-containing disk batteries are a concern because of their ability to cause corrosion and ulceration of the GI mucosa. With a battery ingestion, one would expect signs of inorganic mercury exposure, such as hypersalivation and vomiting, rather than signs of organic mercury poisoning.
  • Digital thermometers are electronic and do not use mercury columns to measure temperature; therefore, they are not factors in mercury poisoning.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Stroke
Illicit drug use
Parkinson disease

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

History and physical examination findings consistent with mercury poisoning are helpful, but blood, urine, and (sometimes) tissue analyses are required to confirm the diagnosis of mercury intoxication. In most laboratories, mercury quantification is not performed on a routine basis; therefore, contact the laboratory to verify the specific collection and precautionary protocols before blood and urine samples are collected.

• Blood analysis
• • Methyl mercury concentrates in RBCs. Consequently, a direct determination of the blood mercury concentrations is essential.
  • The normal range of mercury concentrations in whole blood is 0-10 mcg/L. Early signs and symptoms may occur with concentrations greater than 35 mcg/L.
  • The severity of mercury poisoning is not always correlated with the blood concentration because of the redistribution of mercury in the tissues, specifically those of the central nervous system.
• Urinalysis
• • The detection of mercury in the urine demonstrates that exposure has occurred; however, it does not indicate the severity of mercury poisoning.
  • Methyl mercury is primarily excreted through the feces; the urinary excretion of mercury is minimal.
  • Chelated mercury is excreted primarily through the kidneys. Therefore, urinary assays are useful in monitoring chelation therapy.

Other Tests

• Neuropsychiatric and nerve conduction studies may be helpful.
• Hair analysis can be performed to detect mercury, but its routine use in clinical management is controversial. Proponents state that the concentrations found in organs at autopsy are correlated with concentrations found in scalp hairs. Opponents claim that the concentrations in hair represent past exposure and also that hair can simply absorb mercury from the environment.

Histologic Findings

• Necrosis of the proximal tubules is a common direct renal toxic effect.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The general management measures in Minamata disease are the same as in those of any other toxicologic exposure. After initial assessment and stabilization of the patient's condition, eliminate the patient's exposure to the source of the mercury. Provide general supportive measures, including monitoring, the performance of baseline laboratory studies, and the creation of a differential diagnosis.

Once the neurologic consequences of Minamata disease appear, they are, unfortunately, irreversible. The goal of medical management in Minamata disease is to reduce the total body burden of mercury and minimize further damage.

• Because mercury binds to the body's ubiquitous cellular sulfhydryl groups, chelating agents should be administered early in treatment. These agents are thought to competitively bind the mercury by using its thiol groups. Currently, the best agent for the treatment of Minamata disease is 2,3-dimercaptosuccinic acid (DMSA). Its toxicity is low, and animal trials have shown that it is superior to older chelating agents such as dimercaprol (BAL) and d-penicillamine (DPCN). Even in cases of inorganic mercuric salt exposure, DMSA is preferred over DPCN.
• GI decontamination may be useful only in acute recent ingestions. The absorption of organic forms of mercury, such as methyl mercury, is more than 90% in the GI tract. Inorganic mercuric salts (eg, mercuric chloride) are absorbed at a substantially lower rate of about 10%.
• • Because of the high propensity for neurologic impairment, patients with acute mercury ingestion should undergo gastric lavage with solutions that contain proteins such as those from milk or egg whites.
  • In addition, activated charcoal should be administered although it does not absorb heavy metals well in general. However, a 1948 in vitro study demonstrated that 1 g of activated charcoal could bind 800 mg of mercuric chloride.⁵
• Whole bowel irrigation, along with the administration of polyethylene glycol solution, has been shown to be useful in clearing residual mercury, as depicted on serial abdominal radiography.
• Hemodialysis is not effective in reducing the total-body mercury burden. However, acute renal failure can occur after inorganic mercuric salt ingestion, and hemodialysis may become necessary.

Surgical Care

• Surgery does not have a role in the treatment of Minamata disease; however, in other forms of mercury exposure, surgical intervention is occasionally warranted.
• Rare cases of mercury implantation into the soft tissue either accidentally or in suicide attempts are reported. In all such cases, early definitive surgical excisions of the mercury deposits result in good outcomes with minimal toxicity.

Consultations

• Clinical toxicologists are available for consultation through many regional poison control centers.
• Consultation with a toxicologist is advised in any patient in whom a significant toxicologic exposure to mercury or any other toxin is suspected.

Diet

• In some studies, the levels of mercury in shark, swordfish, and large tuna steaks exceeded the Food and Drug Administration (FDA) safety limit of 1 part per million; however, most other fish sold in the United States have clearly lower levels of approximately 0.3 part per million.
• Because of the high morbidity and mortality rates associated with methyl mercury poisoning, especially in utero, pregnant women and nursing mothers should avoid consuming larger fish because their mercury concentrations tend to be higher than those in smaller fish.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Chelating agents

These are administered early in treatment because mercury binds to the body's ubiquitous sulfhydryl groups. These agents are thought to compete with sulfhydryl groups in binding methyl mercury by using its thiol groups. Chelation has been used to increase the elimination of mercury; however, its effectiveness in preventing or treating neurologic toxicity has not been well evaluated.

Drug Category: Gastrointestinal decontaminants

These agents are empirically used to minimize systemic absorption of the toxin. They may be of benefit only if they are administered within 1-2 h of ingestion.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• All patients in unstable condition should be admitted to an ICU.
• After the patient is admitted, continue supportive measures, decontamination, and careful monitoring.
• In cases of inorganic mercuric salt ingestion, carefully monitor the patient's renal function.

Further Outpatient Care

• After chelation therapy is completed and the patient's condition is stable, careful follow-up with the patient's regular physician is mandatory.
• Monitor the patient's blood mercury concentrations for several months to ensure that the exposure is not ongoing.

In/Out Patient Meds

• After inpatient chelation therapy is completed, outpatient chelation therapy is unnecessary.

Transfer

• After initial stabilization, transfer the patient to a higher level of care is indicated if the capabilities of the treating hospital are inadequate.
• For example, transfer is advised in the following situations:
• • No ICU is available.
  • No chelating agents are in stock.
  • Mercury concentrations cannot be tested in the laboratory.

Deterrence/Prevention

• Minamata disease is best prevented by reducing or eliminating one's consumption of fish caught from bodies of water that are contaminated with high concentrations of mercury.
• Other forms of mercury exposure, such as elemental mercury vapor inhalation, occur when people vacuum or sweep mercury spills in an enclosed space. The proper authorities must handle any spill with the appropriate mercury decontamination kits and procedures.

Complications

• Minamata disease has devastating neurologic consequences as a primary outcome of methyl mercury intoxication; unfortunately, these are relatively resistant to treatment.
• • Acute perioral and facial paresthesias develop.
  • Respiratory distress and nonspecific dermatitis can also occur.
  • Extremity numbness eventually appears along with headache, fatigue, and tremor.
  • Ataxia and dysarthria can also be observed.
  • Severe poisoning eventually causes the patient to lie in a mute semirigid posture that is broken only by episodes of crying or primitive reflexive movements.
• Babies exposed in utero are the most severely affected.
• • They are affected by low birth weight, seizure disorders, profound developmental delay, incomplete visual loss (including tunnel vision), total blindness, and hearing loss.
  • Long-term studies indicate that even prenatal exposure at low concentrations can cause subtle but detectable decrements in the areas of motor function, language, and memory.
  • Children so affected may have long-term stigmata, including motor impairment, visual loss, hearing loss, developmental delay, and seizure disorders.

Prognosis

• Once the neurologic sequelae of Minamata disease are evident, the damage is irreversible, and severe intoxications have been fatal. However, the damage may be minimized if detected early enough.
• Effects of long-term exposure are only now being fully recognized. Most survivors of Minamata disease have chronic neuropathologic conditions such as the following:
• • Ataxia
  • Psychiatric disturbances
  • Sensory loss
  • Chronic paresthesias
• Compared with other patients, babies exposed to Minamata disease in utero have a more dismal prognosis. Their sequelae include the following:
• • Severe developmental delay
  • Low birth weight
  • Persistent cognitive impairment

Patient Education

• Minamata disease typically occurs in areas in which the population depends on seafood as a dietary staple and in areas in which industrial wastes contaminate the drinking water. Educate patients about alternative food sources and about eliminating their intake of contaminated fish.
• Outbreaks of methyl mercury poisoning also have occurred after the introduction of fungicide-treated grain into the food supply. Neither humans nor livestock should eat seed grain treated with mercurial fungicides.
• For excellent patient education resources, visit eMedicine's Poisoning Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning and Activated Charcoal.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose mercury poisoning is the most likely medicolegal pitfall in the management of Minamata disease.
• • The disease is rare in the United States and is uncommon internationally.
  • Testing for mercury exposure is warranted if examination findings consistent with Minamata disease, particularly if the disease occurs in multiple patients without clear etiology, especially true in populations in whom fish is a major part of their diet.
• Consider mercury intoxication in the differential diagnosis when unexplained neuropsychiatric disturbances are coupled with renal abnormalities.

Special Concerns

• Although Minamata disease can affect children of all ages, babies exposed in utero are most severely affected (see Complications).
• • Methyl mercury is lipophilic and readily crosses the blood-brain and placentofetal barriers.
  • Neurologic damage in the form of diffuse and widespread neuronal atrophy is most severe in patients exposed in utero.
• Because of the high morbidity and mortality rates associated with methyl mercury poisoning, especially in utero, pregnant women and nursing mothers should avoid consuming larger fish because their mercury concentrations tend to be higher than those in smaller fish.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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4. Madsen KM, Lauritsen MB, Pedersen CB, et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics. Sep 2003;112(3 Pt 1):604-6. [Medline]. [Full Text].
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10. Isik S, Güler M, Oztürk S, Selmanpakoglu N. Subcutaneous metallic mercury injection: early, massive excision. Ann Plast Surg. Jun 1997;38(6):645-8. [Medline].
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12. Magos L. Three cases of methylmercury intoxication which eluded correct diagnosis. Arch Toxicol. Nov 1998;72(11):701-5. [Medline].
13. Malm O. Gold mining as a source of mercury exposure in the Brazilian Amazon. Environ Res. May 1998;77(2):73-8. [Medline].
14. Mayo Clinic Health Letter. Mercury in fish: concerns shouldn't dampen your appetite. 1996 Apr.
15. Morgan JN, Berry MR, Graves RL. Effects of commonly used cooking practices on total mercury concentration in fish and their impact on exposure assessments. J Expo Anal Environ Epidemiol. Jan-Mar 1997;7(1):119-33. [Medline].
16. Sue, Young-Jin. Mercury. In: Goldfrank LR, Flomenbaum NE, Lewin NA, eds. Goldfrank's Toxicologic Emergencies. 1319-29.
17. Uchino M, Tanaka Y, Ando Y, Yonehara T, Hara A, Mishima I, et al. Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging. J Environ Sci Health B. Sep 1995;30(5):699-715. [Medline].
18. Yotsuyanagi T, Yokoi K, Sawada Y. Facial injury by mercury from a broken thermometer. J Trauma. May 1996;40(5):847-9. [Medline].

Article Last Updated: Jul 21, 2008