ToxCard: Organic Mercury Poisoning

Authors: Ariana Trautmann, MD (Emergency Medicine Resident, Carolinas Medical Center, Charlotte, NC), Ann-Jeannette Geib, MD (Emergency Medicine Attending; Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: James Dazhe Cao, MD (@JamesCaoMD, Associate Professor of EM, Medical Toxicology, UT Southwestern Medical Center, Dallas, TX); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 48-year-old female presents to the ED for months of progressively worsening gait imbalance. She first noticed herself bumping into walls but attributed it to being absent-minded or not paying enough attention to where she was going. Over time, her family noted she wasn’t speaking quite right, and her handwriting had changed, much more illegible than it had previously been. Her vital signs are stable and exam normal until her neurologic exam. She’s noted to have dysmetria, ataxia, and slurred speech but no aphasia. On further conversations with the patient, she tells you that she works as a chemist who handles dimethylmercury and remembers accidentally dropping two drops of liquid chemical on her gloved hand months prior, just a few weeks prior to her symptoms starting.

Questions:

1. What toxic exposure is responsible for the presentation seen above in both the animals and the humans?
2. What are the most common sources of this toxin?
3. What is a potential treatment?

Background:

• Mercury exists in multiple forms (elemental, inorganic, and organic), all of which are toxic, but the degree and manifestation of toxicity is ultimately dependent on the form and route of exposure. For the sake of this discussion, we will focus only on the organic form and its associated toxicity.
• Methylmercury is widely distributed throughout the environment which is reflected by the fact that most people have trace amounts of methylmercury in their bodies (typically less than 10 micrograms/L in whole blood).
  • Sources of organic mercury include:¹
  • Fish
    • High concentrations: Big eye tuna, king mackerel, shark, swordfish
    • Medium concentrations: Albacore tuna, cod, grouper
    • Low concentrations: Pollock, salmon, tilapia
  • Shellfish
  • Pesticides
  • Fungicides
• The use of thimerosal, an organomercury preservative in multidose vaccine vials, has been shown to have no link to the development of autism, but nonetheless is being phased out in an effort to limit exposure to organic mercury compounds wherever possible.²
• Organic mercury includes the compounds dimethylmercury and methylmercury both of which are highly lipophilic.
  • Recall, that high lipophilicity implies that this compound can readily distribute to the brain.
  • These compounds are also readily absorbed from the GI and respiratory tracts.
• Mercury, in all forms, reacts with sulfhydryl groups in intracellular sites ultimately interfering with multiple enzymatic processes.³

 Clinical Presentation:

• Symptoms of acute organic mercury poisoning, which can be nonspecific and often follow a latency period of several weeks, include:^4,5
  • Cardiac symptoms – Non-specific ECG changes (commonly presenting as ST segment depression or prolongation of the QT as the first and second most common findings, respectively)
  • Dermatitis with mucus membrane involvement
  • Gastrointestinal symptoms – Nausea and vomiting
  • Neurologic symptoms – Profound symptoms are more so seen in the chronic neurotoxicity which develops insidiously over weeks and months. Symptoms include tremor, personality changes, emotional lability, gait disturbance, paresthesias, and ataxia. Further, organic mercury readily crosses the placenta where it acts as a teratogen leading to a wide range of birth defects including developmental delay, blindness, seizures, and limb malformation.
  • Respiratory symptoms from a simple cough to frank respiratory distress
• Because symptoms can be so vague, history will be very important! Suspicion should be higher in those who work with products containing mercury (think about our chemist from the case) or have diets that are predominantly fish-based.

Diagnosis and Management:

• Whole blood mercury concentrations are the most useful for diagnosis of organic mercury poisoning, as organic mercury undergoes little urinary excretion. This would be a send-out test and would be unlikely to help us acutely in the ED.
• Patients should undergo a thorough diagnostic evaluation to rule out other causes of their symptoms and findings and may require admission for ambulatory dysfunction, altered mental status, or to eliminate an ongoing source of exposure.⁶
  • Urine heavy metals screens are not recommended for asymptomatic patients.⁶
• The neurotoxicity caused by organic mercury poisoning is permanent, thus, you must act fast. Commonly, we begin to see neurologic sequalae of mercury toxicity when whole body concentrations approach >200 micrograms/L and 24-hour urine levels exceed 100 micrograms/L.⁷
• We are commonly taught that metals are not amenable to treatment with activated charcoal (AC).However, some suggest that there may be some benefit with acute organic mercury ingestion. In short, there is not a whole lot of evidence to support this, but if patient has had a recent ingestion and is not altered, you can consider gastrointestinal decontamination with AC.⁸
• As always, remember to correct electrolyte abnormalities and provide fluid resuscitation as indicated.
• In acute cases of toxicity, attempts can be made to use chelating agents such as succimer or penicillamine in cases of confirmed mercury poisoning or where there is high suspicion. Chelation works by taking the lipophilic dimethylmercury and methylmercury moieties and making them water soluble and thus, readily excreted in the urine.
• Chelation is generally indicated in cases where patients are experiencing symptoms of toxicity (even the vague, non-specific ones) or there are elevated concentrations of mercury in blood.
• Secondary to its high volume of distribution, mercury is not readily dialyzable.
  • However, in extreme cases with highly toxic levels, one could consider plasma exchange if no other suitable alternative exists.^9,10
  • One case report does describe the successful use of hemodialysis plus oral and IV chelation with 2,3-dimercapto-1-propanesulfonic acid (DMPS), with patient recovering to hospital discharge but ultimately unable to function independently. Mercury concentrations were not measured in dialysate. This was a single case whose conclusions need to be studied further.

Case Follow-Up:

This is a real case of a researcher who worked with dimethylmercury in her lab.¹¹ The patient was ultimately treated with succimer, but unfortunately, her neurologic status continued to progressively decline to the point where she became completely unresponsive to verbal and tactile stimuli. She ultimately became comatose and ultimately died. On autopsy, high levels of mercury were found in her frontal lobes, and she globally had extensive neuronal loss. It is suspected that given the exposure occurred months before her presentation, chelation or other therapies could not reverse the damage that had unfortunately already been done. It is now recommended that those who handle dimethylmercury wear “A highly resistant laminate glove (SilverShield or 4H)…under a pair of long-cuffed, unsupported neoprene, nitrile, or similar heavy-duty gloves.”¹²

Clinical Pearls:

• Organic mercury exposure generally occurs from chronic exposure, with a subacute to chronic presentation
• The primary organ system involved is the CNS.
• Exposures are usually from occupational or environmental exposures.
• A medical toxicologist can help with diagnosis. Whole blood mercury concentrations should be measured.
• This condition is difficult to reverse; supportive measures should be undertaken, with chelation considered.

Resources:

1. S. Food and Drug Administration. (2022, February 25). Mercury levels in commercial fish and shellfish (1990-2012). https://www.fda.gov/food/environmental-contaminants-food/mercury-levels-commercial-fish-and-shellfish-1990-2012
2. S. Food and Drug Administration. (2018, February 1). Thimerosal and Vaccines. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/thimerosal-and-vaccines
3. Ajsuvakova OP, Tinkov AA, Aschner M, Rocha JBT, Michalke B, Skalnaya MG, Skalny AV, Butnariu M, Dadar M, Sarac I, Aaseth J, Bjørklund G. Sulfhydryl groups as targets of mercury toxicity. Coord Chem Rev. 2020 Aug 15;417:213343. doi: 10.1016/j.ccr.2020.213343. Epub 2020 May 7. PMID: 32905350; PMCID: PMC7470069.
4. Dahhan SS, Orfaly H, Electrocardiographic Changes in Mercury Poisoning. Am J Cardiol. 1964 Aug;14:178-83. doi: 10.1016/0002-9149(64)90130-4. PMID: 14204762.
5. Winship KA. Organic mercury compounds and their toxicity. Adverse Drug React Acute Poisoning Rev. 1986 Autumn;5(3):141-80. PMID: 3538823.
6. American College of Medical Toxicology. (2015, March 26). Ten Things Physicians and Patients Should Question. https://www.acmt.net/wp-content/uploads/2022/09/ChoosingWisely.pdf
7. Clarkson TW, Magos L, Myers GJ. The toxicology of mercury–current exposures and clinical manifestations. N Engl J Med. 2003 Oct 30;349(18):1731-7. doi: 10.1056/NEJMra022471. PMID: 14585942.
8. Rafati-Rahimzadeh M, Rafati-Rahimzadeh M, Kazemi S, Moghadamnia AA. Current approaches of the management of mercury poisoning: need of the hour. Daru. 2014 Jun 2;22(1):46. doi: 10.1186/2008-2231-22-46. PMID: 24888360; PMCID: PMC4055906.
9. Napp LC, Moelgen C, Wegner F, Heitland P, Koester HD, Klintschar M, Hiss M, Schaper A, Schieffer B, Bauersachs J, Schäfer A, Tongers J. Multimodal Elimination for Intoxication with a Lethal Dose of Organic Mercury. Case Rep Crit Care. 2019 Jan 16;2019:4275918. doi: 10.1155/2019/4275918. PMID: 30792928; PMCID: PMC6354150.
10. Lund ME, Banner W Jr, Clarkson TW, Berlin M. Treatment of acute methylmercury ingestion by hemodialysis with N-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate. J Toxicol Clin Toxicol. 1984 Jul;22(1):31-49. doi: 10.3109/00099308409035080. PMID: 6492229.
11. Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, Toribara TY, Cernichiari E, Clarkson T. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med. 1998 Jun 4;338(23):1672-6. doi:1056/NEJM199806043382305. PMID: 9614258.
12. Blayney MB, Winn JS, Nierenberg DW. Handling dimethylmercury. Chemical & Engineering News (12 May 1997) Vol. 75, No. 19, pp. 7. http://pubsapp.acs.org/cen/safety/19970512.html Accessed 21 November 2022