A variety of illnesses can occur after ingestion of, and less commonly from dermal or inhalational contact with, fish or shellfish toxins. The most common types of seafood-related toxins include ciguatera, scombroid, neurotoxic shellfish poisoning, paralytic shellfish poisoning, and tetrodotoxin. Less commonly encountered toxins will be discussed briefly. Shellfish-induced bacterial gastroenteritis is described (Table II-27).

The mechanism varies with each toxin. Marine toxins are generally tasteless, odorless, and heat-stable. Therefore, cooking the seafood does not prevent illness.

1. Ciguatera. Several ciguatoxins have been identified. They are produced by dinoflagellates, which are then consumed by reef fish. Ciguatoxin binds to voltage-sensitive sodium channels, causing increased sodium permeability and depolarization of excitable membranes. Stimulation of central or ganglionic cholinergic receptors may also be involved.
2. Diarrheic shellfish poisoning is caused by several identified toxins, all of which appear to be produced by marine dinoflagellates. Suspected toxins include okadaic acid, dinophysistoxins, and pectenotoxins. Azaspiracids and yessotoxin are often classified as a diarrheic toxin, although laboratory testing suggests broader cytotoxic activity.
3. Domoic acid, the causative agent for amnesic shellfish poisoning, is produced by phytoplankton, which are concentrated by filter-feeding fish and shellfish. The toxin is a potent glutamate receptor agonist, causing neuroexcitatory responses. It also damages the hippocampus and amygdala through uncontrolled influx of calcium into neurons.
4. Neurotoxic shellfish poisoning is caused by ingestion of brevetoxins, which are produced by “red tide” dinoflagellates. The mechanism appears to involve stimulation of sodium channels, resulting in depolarization of nerve fibers.
5. Palytoxin and its analogs are potent toxins first isolated from the coral genus Palythoa and produced by the dinoflagellate genus Ostreopsis. Through complicated mechanisms, one of which is disruption of the Na⁺/K⁺-ATPase pump, the toxin alters normal ion homeostasis, causing abnormal depolarization and contraction of smooth, skeletal, and cardiac muscles. It is also a potent vasoconstrictor.
6. Paralytic shellfish. Dinoflagellates (“red tide”), and less commonly cyanobacteria from fresh water, produce saxitoxin and 21 other related toxins, which are concentrated by filter-feeding clams and mussels and rarely by nontraditional vectors such as puffer fish, crabs, and lobsters. Saxitoxin binds to voltage-gated, fast sodium channels in nerve cell membranes, blocking neuromuscular transmission.
7. Scombroid. Scombrotoxin is a mixture of histamine and histamine-like compounds produced when histidine in fish tissue decomposes.
8. Tetrodotoxin, produced primarily by marine bacteria, is found in puffer fish (fugu), California newts, some gastropod mollusks, the blue-ringed octopus, horseshoe crab eggs, and some South American frogs. It blocks the voltage-dependent sodium channel in nerve cell membranes, interrupting neuromuscular transmission.

The concentration of toxin varies widely, depending on geographic and seasonal factors. The amount of toxin necessary to produce symptoms is unknown in most cases. An oral dose of 0.1 mcg of ciguatoxin can produce symptoms in a human adult. Saxitoxin is extremely potent; the estimated lethal dose in humans is 0.3-1 mg, and contaminated mussels may contain 15-20 mg. For many marine toxins (eg, ciguatoxin, tetrodotoxin), ingestion of the organs or viscera is associated with greater symptom severity than eating only the fillet.

The onset of symptoms and clinical manifestations vary with each toxin (Table II-28). In the majority of cases, the seafood appears normal, with no adverse smell or taste (scombroid may have a peppery taste; palytoxin may be bitter).

TABLE II-28. FISH AND SHELLFISH INTOXICATIONS

1. Ciguatera. Intoxication produces vomiting and watery diarrhea 1-6 hours after ingestion, followed by headache, malaise, myalgias, paresthesias of the mouth and extremities, ataxia, blurred vision, photophobia, temperature-related dysesthesia (hot and cold sensation reversal), extreme pruritus, hypotension, bradycardia, and rarely seizures and respiratory arrest. Although symptoms generally resolve after several days, some sensory and neuropsychiatric symptoms can last for weeks to months. Ciguatoxins in contaminated fish from the Pacific and Indian Oceans are generally more potent and cause more neurologic symptoms than those in fish from the Caribbean; the latter are associated with more prominent GI symptoms in the initial stages.
2. Diarrheic shellfish poisoning causes nausea, vomiting, stomach cramps, and severe diarrhea. The illness is usually self-limiting, lasting 3-4 days. In animal studies, pectenotoxins cause liver necrosis, and yessotoxins damage cardiac muscle.
3. Domoic acid. Symptoms begin from 15 minutes to 38 hours after ingestion and consist of gastroenteritis accompanied by unusual neurologic toxicity, including fasciculations, mutism, severe headache, hemiparesis, and myoclonus. Coma, seizures, hypotension, and profuse bronchial secretions have been reported with severe intoxication, with a human fatality rate estimated at 3%. Long-term sequelae include persistent severe anterograde memory loss, motor neuropathy, and axonopathy.
4. Neurotoxic shellfish. Onset is within a few minutes to 3 hours. Gastroenteritis is accompanied by paresthesias of the mouth, face, and extremities; muscular weakness and spasms; seizures; and rarely respiratory arrest. Hot and cold sensation reversal has been reported. Inhalation of aerosolized brevetoxins can cause throat irritation, sneezing, coughing, and irritated eyes, and it may worsen respiratory symptoms in persons with asthma. Dermal exposure to contaminated ocean waters or aerosols can cause skin irritation and pruritus.
5. Clinical presentation of palytoxin poisoning may initially mimic that of ciguatera poisoning. However, palytoxin produces greater morbidity and mortality as a result of severe muscle spasms, seizures, rhabdomyolysis, coronary vasospasm, hypertension, arrhythmias, and acute respiratory failure. Severe hyperkalemia and hyperphosphatemia were seen in a fatal case of palytoxin poisoning confirmed by laboratory analysis. Milder versions of human poisonings have occurred from dermal and inhalational exposure to the toxin; respiratory symptoms include hypoxia and persistent dyspnea. Clupeotoxism, a highly toxic marine poisoning associated with ingestion of sardines and herring, is thought to be caused by palytoxin. Symptoms include abrupt onset of generalized paralysis, convulsions and acute respiratory distress.
6. Paralytic shellfish. Vomiting, diarrhea, and facial paresthesias usually begin within 30 minutes of ingestion. Headache, myalgias, dysphagia, weakness, and ataxia have been reported. In serious cases, respiratory arrest may occur after 1-12 hours.
7. Scombroid. Symptoms begin rapidly (minutes to 3 hours) after ingestion. Gastroenteritis, headache, and skin flushing sometimes are accompanied by urticaria, bronchospasm, tachycardia, and hypotension.
8. Tetrodotoxin. Symptoms occur within 30-40 minutes after ingestion and include vomiting, paresthesia, salivation, twitching, diaphoresis, weakness, and dysphagia. Hypotension, bradycardia, flaccid paralysis, and respiratory arrest may occur up to 6-24 hours after ingestion.
9. Other unusual poisonings from marine toxins include Haff disease, unexplained rhabdomyolysis after ingestion of buffalo fish or salmon; hallucinatory fish poisoning (ichthyoallyeinotoxism), characterized by hallucinations and nightmares from ingestion of several families of fish (sometimes known locally as “dreamfish”); and chelonitoxism, a potentially fatal poisoning involving multiorgan-system failure resulting from ingestion of marine turtles. The causative toxins in these poisonings have not been definitively identified.

Depends on a history of ingestion and is more likely to be recognized when multiple victims present after consumption of a seafood meal. Scombroid may be confused with an allergic reaction because of the histamine-induced urticaria.

1. Specific levels are generally unavailable. However, when epidemic poisoning is suspected, local and federal health agencies may provide sample analysis. The Food and Drug Administration can conduct ciguatoxin testing of suspected fish.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, CPK, arterial blood gases, ECG monitoring, and stool for bacterial culture.

1. Emergency and supportive measures. Most cases are mild and self-limited and require no specific treatment. However, because of the risk for respiratory arrest, all patients should be observed for several hours (except patients with diarrheic shellfish poisoning).
   1. Maintain an open airway and assist ventilation if necessary.
   2. Replace fluid and electrolyte losses from gastroenteritis with IV crystalloid fluids.
2. Specific drugs and antidotes
   1. Ciguatera. There are anecdotal reports of successful treatment with IV mannitol 20%, 0.5-1 g/kg infused over 30 minutes, particularly when instituted within 48-72 hours of symptom onset. Although a randomized study showed no difference in outcome between mannitol and saline therapy, inclusion of late-presenting patients may have clouded the data. Gabapentin, 400 mg 3 times daily, has been anecdotally reported to relieve symptoms of neuropathy.
   2. Neurotoxic shellfish.Atropine may help reverse bronchospasm and bradycardia due to brevetoxin.
   3. Scombroid intoxication can be treated symptomatically with both H₁ and H₂ histamine blockers, such as diphenhydramine and cimetidine, 300 mg IV. Rarely, bronchodilators may also be required.
   4. Tetrodotoxin. Some authors recommend IV neostigmine for the treatment of muscle weakness. However, its effectiveness is unproven, and its routine use is not recommended.
3. Decontamination procedures are not indicated in most cases. However, consider using activated charcoal if immediately available after ingestion of a highly toxic seafood (eg, fugu fish).
4. Enhanced elimination. There is no role for these procedures.