Brenna M. Farmer
Seafood has been a dietary staple, safely eaten for thousands of years. However, occasional poisoning from seafood can result in many clinical syndromes, which mainly involve the gastrointestinal (GI) or neurologic systems, and with the popularity of world travel and importation of seafood, seafood toxin–related syndromes may be encountered anywhere. For emergency physicians, understanding the diagnosis and treatment of these syndromes is essential.
Ciguatera poisoning follows ingestion of large carnivorous fish containing high concentrations of ciguatoxin, which is produced primarily by the dinoflagellate, Gambierdiscus toxicus. G. toxicus is found in tropical and subtropical waters along coral reefs. Ciguatoxin is a colorless, tasteless, heat- and acid-stable, lipid-soluble polyether that bioaccumulates in the organs (particularly, the liver and gonads) of predator fish (1). Outbreaks typically occur in the Caribbean, Australia, and the South Pacific but have been reported worldwide, with more than 400 species of fish, mostly reef fish, implicated. Barracuda, grouper, red snapper, amberjack, eel, sea bass, and Spanish mackerel are most commonly involved. Fish larger than 2 kg are more likely to be contaminated with significant quantities of toxin. Ciguatoxin acts to open sodium channels, which increases sodium permeability through voltage-gated sodium channels (1).
Scombroid poisoning occurs with ingestion of fish containing histamine, also known as scombrotoxin (1). Bacteria under the scales of the fish convert histidine, a normal component of fish muscle, into histamine when the fish is poorly stored or improperly refrigerated. The bacteria are commonly found on the surface of dark or red-fleshed fish of the Scombroidae family (tunas, skipjack, bonito, and mackerels) and other fish with dark flesh, such as dolphin fish (mahi mahi), bluefish, amberjack (yellowtail), herring, sardines, and anchovies. Scombrotoxin is heat-stable and can sometimes impart a metallic or peppery taste (1). Patients taking isoniazid or MAOI, inhibitors of diamine oxidase, are more sensitive to scombrotoxin. The histamine content of spoiled flesh can vary considerably throughout a fish, being highest near the gut cavity. Individual sensitivity to scombroid poisoning also varies considerably; females are thought to be more susceptible.
Tetrodotoxin is a heat-stable, water-soluble neurotoxin found in the skin and viscera of puffer fish (saltwater and freshwater varieties), porcupine fish, sunfish, toadfish, the blue-ringed octopus, some species of salamanders, and Atelopid frogs. Puffer fish, the most common source of tetrodotoxin, is eaten as the delicacy fugu in some Asian countries. Although tetrodotoxin is concentrated in the fish’s skin and internal organs, it can be found in all parts of the fish. Most poisonings still occur in Japan, where sushi chefs must be licensed in the proper technique of preparing puffer fish to minimize risk of death with improper preparation. Tetrodotoxin is a sodium-channel inhibitor and reduces neuronal conduction (1,2). Tetrodotoxin bioaccumulates in the liver and gonads of the puffer fish like ciguatera (1).
Paralytic shellfish poisoning results from the ingestion of bivalve and gastropod mollusks (mussels, clams, oysters, scallops, and cockles) and occasionally some univalve mollusks, starfish, crustaceans, and fish (including puffer fish, which are more commonly associated with tetrodotoxin). These creatures become toxic when dinoflagellates, especially Gonyaulax spp., multiply explosively, causing red tides. Red tides are visible marine overgrowths of phytoplankton and dinoflagellates. Ingestion of filter-feeding shellfish from regions with red tides can lead to epidemic poisonings, such as paralytic shellfish poisoning. Toxic shellfish are commonly found in the cold, temperate waters of the Americas, the western coast of Europe, and the coastal waters of Japan but are increasingly reported in warmer climates. Outbreaks have occurred in Nova Scotia, New Brunswick, Maine, and Alaska (3). The toxins do not harm shellfish but are concentrated in viscera and can take several weeks to be eliminated. Seabirds, several fish species, and mammals are susceptible to poisoning. Saxitoxin, a potent, heat-stable, water-soluble neurotoxin of paralytic shellfish poisoning, acts by blockading fast sodium channels in nerve and muscle during depolarization, and results in a conduction block that principally affects motor neurons and muscle (1). There is no reliable taste, smell, or color to identify contaminated shellfish.
Another seafood toxin–associated illness seen with red tides is neurotoxic shellfish poisoning, which also results in a ciguatera-like syndrome but is generally less severe. It is caused by brevetoxins from Ptychodiscus brevis, a dinoflagellate found off the coast of southeastern North America and Western Europe during algae blooms. The toxins are accumulated by clams and oysters. Brevetoxin opens sodium channels similarly to ciguatoxin (1).
A third shellfish poisoning, amnestic shellfish poisoning, a toxic encephalopathy, is caused by ingestion of shellfish, mainly mussels, containing domoic acid (1). The largest outbreak was in Prince Edward Island, Canada. The heat-stable toxin is derived from Nitzschia pungens, another dinoflagellate that causes red tides. Domoic acid acts as an excitatory neurotransmitter at the glutamate receptor (4).
Diarrheic shellfish poisoning can occur after ingestion of mussels, Dinophysis spp., containing okadaic acid and dinophysistoxins. Outbreaks have been reported in the Netherlands, Japan, Europe, and most recently in Greece (1,5). Okadaic acid and dinophysistoxins are lipophilic, fat-soluble, and inhibit essential protein phosphatases (1).
A syndrome similar to diarrheic shellfish poisoning occurs with ingestion of azaspiracid-contaminated mussels, Mytilus edulis. Outbreaks have occurred in the Netherlands and Ireland. Azaspiracid is a lipophilic, highly oxygenated polyether found in Protoperidinium spp., another dinoflagellate (6).
Another poorly understood seafood toxic syndrome is hallucinatory fish poisoning, ichthyoallyeinotoxism. It is reported around the world, particularly in areas near the Indian and Pacific Oceans and the Mediterranean Sea. The sea bream, Sarpa salpa, related to the porgie is implicated in carrying an unknown toxin responsible for this type of seafood poisoning (7).
CLINICAL PRESENTATION
Seafood toxin poisoning typically affects the GI and neurologic systems.
Ciguatera poisoning typically occurs 2 to 30 hours after ingestion of ciguatoxic fish. Patients characteristically present with circumoral and/or extremity paresthesias, arthralgias, myalgias, diarrhea, vomiting, bradycardia, and pruritus. A classic, though uncommon, finding is hot–cold temperature sensation reversal in which a burning or painful sensation is associated with touching cold objects (8). Patients may present initially with only neurologic symptoms; which may be delayed up to 72 hours after ingestion or may occur without GI symptoms. Hypotension is common and may be due to fluid loss, bradycardia, peripheral vasodilatation, or myocardial depression. Symptoms vary among different patients and depend on where the fish were caught and what parts were eaten. More severe toxicity, especially hypotension and bradycardia, occurs in patients who have been previously poisoned by ciguatera. Other common neurologic symptoms include asthenia, paresis, tremors, and pain affecting the joints, head, and abdomen. The paresthesias do not conform to dermatomal or peripheral nerve distribution. A sensation of looseness of the teeth is another unusual symptom. Insomnia, neurosis, depression, and hallucinations may occur. Other features include dyspnea, diaphoresis, salivation, tearing, chills, neck stiffness, pruritus, rashes, and tachycardia. In pregnant patients, violent fetal movements have been described. Less commonly, transient blindness, convulsions, rhabdomyolysis, polymyositis, or paralysis may occur. Death, although uncommon, may result from severe dehydration or cardiac or respiratory failure (8).
The onset of scombroid poisoning is normally within 1 hour of ingestion. The presentation is similar to, but generally less severe than, IgE-mediated allergic (anaphylactic) or anaphylactoid reactions. Patients experience intense flushing of the upper trunk and face, nausea, vomiting, hives, pruritus, tachycardia, bronchospasm, and occasionally hypotension. Severe reactions, such as bronchospasm, hypotension, and supraventricular tachyarrhythmias, are more likely to occur in patients with pre-existing cardiac or respiratory disease. Findings usually resolve within 6 to 12 hours from the time of ingestion.
Patients with tetrodotoxin poisoning usually present within 10 to 45 minutes after ingesting the toxic seafood. However, case presentations delayed up to 20 hours are reported. Early symptoms include a feeling of exhilaration. Four stages of poisoning have been described. Initially, circumoral paresthesias, salivation, nausea, and vomiting occur, followed by peripheral paresthesias and numbness. Sensory symptoms then become more generalized, with ascending paralysis of the extremities, although deep-tendon reflexes remain intact. In the third stage, ataxia and paralysis of peripheral and bulbar muscles occur. Finally, respiratory muscles are affected, although patients may still be conscious. Patients may become unconscious and completely paralyzed, with dilated nonreactive pupils and loss of all brainstem reflexes. Because of its effect on the sodium channel, cardiac arrhythmias, including A-V blocks, are also reported (2). Recovery occurs over a period of days and, unless complicated by anoxia, is complete. Death is usually due to paralysis of the respiratory muscles.
Paralytic shellfish poisoning occurs within minutes of ingestion and usually begins with neurologic symptoms including perioral, hand, and finger paresthesias, with associated nausea and abdominal pain. These are followed by paresthesias of the face and extremities and progressive muscle paralysis. Bulbar muscles are often affected, causing dysarthria, dysphagia, diplopia, and loss of the gag reflex. Other features include vertigo, ataxia, transient blindness, altered temperature perception, hypotension, headache, and low back pain. The paresthesias then become generalized, and a progressive paralysis including loss of deep-tendon reflexes and fixed-dilated pupils develops. Respiratory paralysis may be fatal without rapid intervention. Complete recovery typically occurs within 24 to 48 hours (3).
Neurotoxic shellfish poisoning causes a syndrome similar to ciguatera. Circumoral paresthesias that generalize, headache, tachycardia, and muscle cramps are common. Nausea, abdominal pain, vomiting, and diarrhea also occur. Seizures and coma have occurred with severe poisonings.
Amnestic shellfish poisoning also produces neurologic and GI findings, with onset of effects from minutes to 38 hours. Abdominal pain, nausea, and diarrhea, with loss of memory, severe headache, confusion, and disorientation commonly occur. Severe intoxication can result in seizures and coma. Improvement occurs 24 hours to 12 weeks after ingestion of mussels containing domoic acid (4).
The main symptoms from diarrheic shellfish poisoning and azaspiracid poisoning are GI. Onset occurs from 30 minutes to 10 hours after ingestion of seafood (5), and the predominant effects are diarrhea, nausea, vomiting, abdominal cramps, and chills. Patients usually do not have a fever (5,6). Full recovery from this self-limited illness occurs within 3 to 4 days (1).
Ichthyoallyeinotoxism, hallucinatory fish poisoning, begins within minutes to 2 hours of ingestion of toxic fish. Initial symptoms resemble ethanol intoxication and include ataxia, incoordination, and general malaise/weakness. Within hours, patients report hallucinations (visual and/or auditory) and become delirious. Nightmares can occur. Some patients experience less common symptoms of vomiting and diarrhea. Symptoms usually resolve within 24 to 36 hours, although weakness can persist for days (7).
DIFFERENTIAL DIAGNOSIS
Patients who present with illness related to seafood toxins generally have a predominance of GI and neurologic signs and symptoms. The clinical presentations of ciguatera, neurotoxic shellfish, tetrodotoxin, and paralytic shellfish poisoning may be difficult to distinguish, as all may involve symptoms of paresthesias, weakness, and ataxia. Geographic location, predominant symptoms, and the type of fish eaten are used to determine the specific etiology. A common shellfish origin has been found for toxins associated with tetrodotoxin and paralytic shellfish poisoning.
Infectious viral and bacterial gastroenteritis must also be considered in any patient presenting with GI complaints. Common seafood pathogens include hepatitis A, Norwalk virus, and Vibrio spp. (including V. cholerae, V. parahaemolyticus, and V. vulnificus).
Encephalitis, meningitis, Guillain–Barre, botulism, and transient ischemic attack, or stroke, should be considered in patients presenting with paralysis or other neurologic findings. In patients presenting with seizures, electrolyte and metabolic abnormalities, other toxins or an underlying seizure disorder should also be considered.
Anaphylaxis to seafood should be considered, especially in patients with signs and symptoms of scombroid poisoning. A metallic or strong peppery taste to the fish and the type of fish may distinguish scombroid from a true allergic reaction. Skin flushing can occur with scombroid poisoning but also with red man syndrome, niacin ingestion, monosodium glutamate ingestion, and ethanol–disulfiram interactions.
ED EVALUATION
One should obtain a history of foods ingested in patients with the combination of GI and neurologic symptoms. Special attention should be paid to the type of seafood ingested, locale, time of ingestion, and onset of symptoms. The origin of the seafood should be identified if possible, as this may help to differentiate poisonings specific to certain regions. Public health officials may be able to assist in this process and provide information about similar cases or known quarantined fishing areas.
Physical examination should focus on vital signs, respiratory function, and the neurologic examination, including deep-tendon reflexes and sensation. Patients with tachycardia or hypotension should be evaluated for hypovolemia.
KEY TESTING
• Fingerstick glucose: To assess for cause of altered mental status
• Electrolytes: To exclude nontoxin-related neurologic problems, or disturbances due to vomiting and diarrhea
• Forced vital capacity/negative inspiratory force: To assess for severity of neuromuscular involvement or impending respiratory failure in patients with severe neurologic involvement
• Seafood toxin assay: To assess for toxin in the seafood (if any food is available)
ED MANAGEMENT
Supportive care is the mainstay of therapy in all seafood toxin–related syndromes. Airway, breathing, and circulation (ABCs) should be addressed initially. Patients should have intravenous access and cardiac monitoring as appropriate. In patients with abnormal ventilation as demonstrated by decreased vital capacity, negative inspiratory force, or hypopnea or apnea, intubation and mechanical ventilation should be considered. Abnormal heart rhythms such as bradycardia should be addressed (see Chapter 84, Bradydysrhythmias). Patients with tachycardia or hypotension should initially receive intravenous saline, but vasopressors such as dopamine, norepinephrine, or phenylephrine may be required if hypotension is unresponsive to saline.
In patients who may still have seafood in their stomach, activated charcoal (1 g/kg) should be considered. Antiemetics should be used for nausea and vomiting.
Specific therapy has been used in ciguatera poisoning. Although there are conflicting data on its efficacy, mannitol, 1 g/kg, is often recommended for patients with severe neurologic toxicity such as coma (9,10). Amitriptyline, which may act by blocking sodium channels, usually provides some relief from the chronic neurologic symptoms of ciguatera poisoning. Other agents used with varying degrees of success include fluoxetine, nifedipine, vitamins B12and C, calcium gluconate (1 to 3 g intravenously over 24 hours), lidocaine, and tocainide. Two patients who were treated with gabapentin (400 mg orally three times daily) experienced a rapid improvement and recurrence of symptoms after therapy was discontinued. Other medications commonly used for neuropathic pain have been used for persistent paresthesias. Indomethacin and cyproheptadine are commonly used to relieve arthralgia and pruritus, respectively.
For scombroid poisoning, treatment includes H1- and H2-receptor antagonists. H2-blockers such as cimetidine appear more effective than type 1 blockers such as diphenhydramine (3). Epinephrine may benefit the rare severely ill patient with hypotension who is not responsive to intravenous saline or with bronchospasm not responsive to albuterol. Corticosteroids are of little benefit, as this poisoning is due to histamine only (i.e., no secondary mediators such as leukotrienes are released). Once stabilized, patients with scombroid poisoning can be discharged on oral antihistamines for 48 hours.
Benzodiazepines are useful to manage the disturbing hallucinations and nightmares experienced by patients with hallucinatory fish poisoning. Edrophonium and neostigmine have been used to reverse motor paralysis due to tetrodotoxin poisoning but have not been studied in controlled trials.
Besides supportive care, prevention is the best treatment of all. Fish weighing >2 kg or of those types known to be frequently affected should be avoided to prevent ciguatera. Patients should also avoid eating specific organs in which the toxins accumulate, such as the liver and gonads for ciguatera and tetrodotoxin. The government bans the sale of certain fish known to carry the toxin. In Miami, barracuda is banned from sale due to the risk of ciguatera poisoning. The local health department also periodically tests shellfish for certain toxins and when red tides occur, and quarantines are instituted as appropriate.
CRITICAL INTERVENTIONS
• Assess ABCs and evaluate pulmonary function early with measurements of forced vital capacity and negative inspiratory force.
• Provide supportive care, including antiemetics for nausea and vomiting and intravenous saline for dehydration and hypotension.
• Treat scombroid poisoning with H1- and H2-receptor antagonists.
• Consult a regional poison center and/or public health officials for current treatment advice and to report outbreaks.
DISPOSITION
Most patients may be discharged home after evaluation and supportive treatment in the emergency department. Outpatient follow-up should be arranged. Patients with abnormal vital signs, neurologic symptoms, persistent vomiting, or inability to tolerate oral fluids should be admitted to the hospital. Patients with neurologic symptoms or those at risk for development of respiratory weakness or paralysis should be admitted to an intensive care unit for close monitoring. Local or state departments of health should be notified of all cases of suspected seafood poisoning, as timely intervention may prevent additional exposures.
Common Pitfalls
• Failure to consider seafood poisonings in patients with gastroenteritis and/or neurologic symptoms.
• Failure to admit patients with neurologic findings for monitoring.
• Failure to treat scombroid poisoning with antihistamines.
REFERENCES
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