Introduction
Background
Poisoning with the neurotoxin tetrodotoxin (TTX) occurs after ingestion of various species of puffer fish (see Media file 1). The flesh of the puffer fish (ie, fugu) is considered a delicacy in Japan. It is prepared by chefs specially trained and certified by the government to prepare the flesh free of the toxic liver, gonads, and skin. Despite these precautions, many cases of tetrodotoxin poisoning are reported each year in patients ingesting fugu.
Poisonings usually occur after eating fish caught and prepared by uncertified handlers.
The toxic dose is not clear because puffer fish have different concentrations of tetrodotoxin. A dose of 1-2 mg of purified toxin can be lethal. Reported cases from the Centers for Disease Control and Prevention (CDC) have documented toxicity with ingestion of as little as 1.4 ounces of puffer fish.
Tetrodotoxin also is found in the gastropod mollusc; in the eggs of horseshoe crabs; in newts of the genus Taricha; in the skin of Atelopid frogs; and in the skin and viscera of porcupine fish, globefish, balloon fish, blowfish, sunfish, toadfish, blue-ringed octopus, and some species of salamanders.
Pathophysiology
Puffer fish contain the potent neurotoxin tetrodotoxin. TTX is thought to be synthesized by a bacterial or dinoflagellate species associated with the puffer fish.
The toxin is concentrated in the liver, gonads, and skin. The level of toxicity is seasonal, and, in Japan, fugu is served only from October through March.
Tetrodotoxin is a heat-stable (except in alkaline environments) and water-soluble nonprotein.
Tetrodotoxin is a heterocyclic, small, organic molecule that acts directly on the electrically active sodium channel in nerve tissue (see Media file 2). Tetrodotoxin blocks diffusion of sodium through the sodium channel, preventing depolarization and propagation of action potentials in nerve cells.
All of the observed toxicity is secondary to the action potential blockade. Tetrodotoxin acts on the central and the peripheral nervous systems (ie, autonomic, motor, sensory nerves).
Tetrodotoxin also stimulates the chemoreceptor trigger zone in the medulla oblongata and depresses the respiratory and vasomotor centers in that area.
Recent study using tetrodotoxin therapeutically shows that tetrodotoxin used in conjunction with bupivacaine prolonged the local anesthetic effect.1 If tetrodotoxin begins to be used clinically, the incidence of toxicity may increase.
Frequency
United States
Reports of tetrodotoxin poisoning are rare in the United States, but a 1996 report in the Morbidity and Mortality Weekly Report (MMWR) documents 3 cases of tetrodotoxin toxicity from persons who ingested contaminated fugu imported by a coworker from Japan.2
International
Despite the careful training and certification of fugu chefs in Japan, cases of mortality and morbidity from puffer fish ingestion continue to be reported. Estimates vary, but up to 50 deaths may occur each year from tetrodotoxin poisoning in Japan.
Mortality/Morbidity
Mortality rates are difficult to calculate, but estimates of mortality approach 50%, even with modern supportive medical care. Patients who live through the acute intoxication (ie, first 24 h) usually recover without residual deficits. Recovery takes days to occur.
Race
No known racial predilection exists. However, the poisoning is more common in Japanese people because of their dietary preferences for fugu.
Clinical
History
- The first symptoms occur 15 minutes to several hours postingestion of tetrodotoxin-containing food. A recent report on toxicity found that initial symptoms may occur up to 20 hours after ingestion.
- Initial symptoms include lip and tongue paresthesias, followed by facial and extremity paresthesias and numbness.
- Salivation, nausea, vomiting, and diarrhea with abdominal pain develop early.
- Motor dysfunction with weakness, hypoventilation (may be from dysfunction of central and peripheral nervous systems), and speech difficulties then develop. A rapid ascending paralysis occurs over 4-24 hours. Extremity paralysis precedes bulbar paralysis, which is followed by respiratory muscle paralysis. Deep tendon reflexes are preserved early in the course of paralysis.
- Finally, cardiac dysfunction with hypotension and dysrhythmias (bradycardia), central nervous system (CNS) dysfunction (eg, coma), and seizures develop. Patients with severe toxicity may have deep coma, fixed nonreactive pupils, apnea, and loss of all brain stem reflexes.
- Death can occur within 4-6 hours. Typically, death occurs from respiratory muscle paralysis and respiratory failure.
Physical
- Loss of sensory and motor neuron function is a prominent finding.
- Ascending paralysis with respiratory depression.
- Cyanosis occurs with respiratory failure.
- Hypotension can occur with myocardial dysfunction.
- Cardiac rhythm disturbances, especially bradycardia, atrioventricular (AV)–nodal block, and bundle-branch block, can be life threatening.
- GI effects are not prominent, but vomiting and abdominal tenderness can occur.
Causes
- Ingestion of tetrodotoxin causes the syndrome.
- Almost all toxicity is caused by the ingestion of fugu, but other species of animals have been shown to produce tetrodotoxin (eg, California newt, parrot fish, blue-ringed octopus). A death from ingestion of tetrodotoxin from a California newt has been documented.
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References
Padera RF, Tse JY, Bellas E, Kohane DS. Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity. Muscle Nerve. Dec 2006;34(6):747-53. [Medline].
San Diego Department of Environmental Health, FDA. Tetrodotoxin poisoning associated with eating puffer fish transported from Japan--California, 1996. MMWR Morb Mortal Wkly Rep. May 17 1996;45(19):389-91. [Medline].
Rivera VR, Poli MA, Bignami GS. Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice. Toxicon. Sep 1995;33(9):1231-7. [Medline].
Chang FC, Spriggs DL, Benton BJ, et al. 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs. Fundam Appl Toxicol. Jul 1997;38(1):75-88. [Medline].
Ahasan HA, Mamun AA, Karim SR, et al. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singapore Med J. Feb 2004;45(2):73-4. [Medline].
FDA/CFSAN resources page. Pufferfish poisoning. Food and Drug Administration Web site. Available at: http://vm.cfsan.fda.gov/~mow/chap39.html. Accessed January 20, 2005. [Full Text].
How CK, Chern CH, Huang YC, et al. Tetrodotoxin poisoning. Am J Emerg Med. Jan 2003;21(1):51-4. [Medline].
Karalliedde L. Animal toxins. Br J Anaesth. Mar 1995;74(3):319-27. [Medline].
Lange WR. Puffer fish poisoning. Am Fam Physician. Oct 1990;42(4):1029-33. [Medline].
Mills AR, Passmore R. Pelagic paralysis. Lancet. Jan 23 1988;1(8578):161-4. [Medline].
Sims JK, Ostman DC. Pufferfish poisoning: emergency diagnosis and management of mild human tetrodotoxication. Ann Emerg Med. Sep 1986;15(9):1094-8. [Medline].
Sun KO. Management of puffer fish poisoning. Br J Anaesth. Oct 1995;75(4):500. [Medline].
Xu QH, Zhao XN, Wei CH, Rong KT. Immunologic protection of anti-tetrodotoxin vaccines against lethal activities of oral tetrodotoxin challenge in mice. Int Immunopharmacol. Jul 2005;5(7-8):1213-24. [Medline].
Further Reading
Keywords
TTX, Japanese puffer fish, fugu, tetrodotoxin, tetrodotoxin toxicity, tetrodotoxin exposure, tetrodotoxin poisoning, tetrodotoxin ingestion, neurotoxin
