Ingestion of pufferfish (called fugu or "river pig" in Japanese), considered to be one of the most delicious fish in Japan, can lead to life-threatening intoxication that is often described in the literature as fugu poisoning [1] [2] [3]. The pathogenesis stems from the presence of tetrodotoxin (TTX) in the internal organs of the fugu (the liver, the intestines, and gonads, but also the skin), a powerful heat-stable neurotoxin that blocks sodium channel action, thus diminishing neuronal activity [1] [4]. In most cases, the onset of symptoms appears shortly after ingestion of the toxin (<30 minutes) [1], with initial signs being gastrointestinal complaints (nausea, vomiting) and mild paresthesia of the perioral area [2] [3]. As the activity of TTX increases, paresthesia and weakness spread to the chest and both upper and lower extremities, whereas headaches, vertigo, ataxia, and blurred vision also appear [2] [3] [4]. Other common complaints are diaphoresis, dysphagia, excessive salivation, seizures, and muscle spasms, whereas hypotension, bradycardia, and fixed dilated pupils are markers of severe poisoning [2] [4]. Respiratory difficulties, arising from progressive paralysis of the breathing muscles, develop in advanced stages, and can be fatal within 24 hours [3] [4]. In fact, fatality rates of severe fugu poisoning are estimated at 60% according to certain reports [4].

• El Salvador

  Cholera associated with food transported from El Salvador -- Indiana, 1994. MMWR 1995; 44:385-6. Table_1 Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size. TABLE 1. [cdc.gov]

• Dyspnea

  […] activity and include (in order of appearance): numbness of lips and tongue dizziness tingling increasing paraesthesias gastrointestinal symptoms such as nausea, vomiting and diarrhea (often severe) impaired heart rate paralysis: impaired speech, increasing dyspnea [flipper.diff.org]

• Food Poisoning

  Nationwide, there were 338 food poisoning cases in Japan related to fugu consumption that killed 23 people from 2000 to 2009. [japantimes.co.jp]

  The men, whose names were not released because of medical confidentiality laws, were lucky: They survived severe food poisoning from a notorious source--fugu. [articles.latimes.com]

  Despite careful preparation, fugu remains a common cause of fatal food poisoning in Japan, accounting for approximately 50 deaths annually (7). [cdc.gov]

  How to spot food poisoning The symptoms of fugu poisoning are slightly different from the typical food poisoning symptoms. [es.favy-jp.com]

  Puffer fish account for the majority of Japan's food poisoning deaths but the delicacy shows no sign of dying out, although it is heavily regulated. [dailymail.co.uk]

• Chest Pain

  Chest pains followed, as did shaking, nausea and vomiting. Shortly thereafter, his legs buckled and he collapsed. Paramedics called to the Japanese restaurant in San Diego recognized his symptoms as a classic food poisoning case. [articles.latimes.com]

  Other manifestations include salivation, muscle twitching, diaphoresis, pleuritic chest pain, dysphagia, aphonia, and convulsions. Severe poisoning is indicated by hypotension, bradycardia, depressed corneal reflexes, and fixed dilated pupils. [cdc.gov]

• Red Eye

  Some Malays pretend there are different species which are more deadly than others; those with the “red eyes” ( mata mirah ) are certain to cause death, and the proceedings as in the case of the fortman above mentioned would, if he had partaken of the [leminhkhai.wordpress.com]

• Flushing

  Approximately 10-15 minutes later, he had onset of tingling in his mouth and lips followed by dizziness, fatigue, headache, a constricting feeling in his throat, difficulty speaking, tightness in his upper chest, facial flushing, shaking, nausea, and [cdc.gov]

• Flushing

  Approximately 10-15 minutes later, he had onset of tingling in his mouth and lips followed by dizziness, fatigue, headache, a constricting feeling in his throat, difficulty speaking, tightness in his upper chest, facial flushing, shaking, nausea, and [cdc.gov]

• Paresthesia

  As the activity of TTX increases, paresthesia and weakness spread to the chest and both upper and lower extremities, whereas headaches, vertigo, ataxia, and blurred vision also appear. [symptoma.com]

  Paresthesias begin 10-45 minutes after ingestion, usually as tingling of the tongue and inner surface of the mouth. Other common symptoms include vomiting, lightheadedness, dizziness, feelings of doom, and weakness. [cdc.gov]

  Toxic manifestations start with perioral paresthesias, quickly followed by generalized weakness, ascending paralysis, and respiratory failure. To read my Emergency Medicine News column on fugu, click here. [thepoisonreview.com]

  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. [podolsky.ca]

  If a rapid onset of one of the following neurologic and gastrointestinal signs or symptoms occurs, the clinical description for tetrodotoxin poisoning has been met: 1) oral paresthesias (might progress to include the arms and legs), 2) cranial nerve dysfunction [lamag.com]

• Flaccid Paralysis

  paralysis” – and unable to speak, but your head is weirdly clear. [ranker.com]

Because of the high fatality rate of fugu poisoning, a prompt diagnosis could be life-saving. For this reason, the physician must conduct a thorough physical examination, and most importantly, obtain a detailed patient history, which is perhaps the vital step in the workup [3] [4]. Fugu poisoning has been reported mainly in countries of Southeast Asia (Bangladesh, Taiwan, Cambodia, Hong Kong), but cases in the United States were also described in the literature [3] [4] [5] [6]. Very recent ingestion of pufferfish should be disclosed during the interview, whereas a complete neurological assessment provides sufficient clues to make a presumptive diagnosis of a sudden and progressive paralysis. Since several outbreaks have occurred in association with TTX from fugu [1], physicians must check if similar symptoms are present in friends or persons who ate the same food. The diagnosis of fugu poisoning rests on clinical grounds, but when possible, levels of TTX can be measured in the patient's serum or urine (or in leftover food, if available) [3] [4] [6] [7]. Mass spectrometry (MS) is able to detect tetrodotoxin in these samples and confirm the diagnosis [7].

1. Lago J, Rodríguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses. Long P, ed. Mar Drugs. 2015;13(10):6384-6406.
2. Ahasan HA, Mamun AA, Karim SR, Bakar MA, Gazi EA, Bala CS. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singap Med J. 2004;45:73–74
3. Yong YS, Quek LS, Lim EK, Ngo A. A Case Report of Puffer Fish Poisoning in Singapore. Case Reports in Medicine. 2013;2013:206971.
4. Centers for Disease Control and Prevention (CDC). Tetrodotoxin poisoning associated with eating puffer fish transported from Japan--California 1996. MMWR Morb Mortal Wkly Rep. 1996;45(19):389-391.
5. Ngy L, Taniyama S, Shibano K, Yu C-F, Takatani T, Arakawa O. Distribution of tetrodotoxin in puffer fish collected from coastal waters of Sihanouk Ville, Cambodia. Journal of the Food Hygienic Society of Japan. 2008;49(5):361–365.
6. Homaira N, Rahman M, Luby SP, et al. Multiple outbreaks of puffer fish intoxication in Bangladesh, 2008. American Journal of Tropical Medicine and Hygiene. 2010;83(2):440–444.
7. Leung KSY, Fong BMW, Tsoi YK. Analytical challenges: determination of tetrodotoxin in human urine and plasma by LC-MS/MS. Mar Drugs. 2011;9(11):2291–2303.