Fish and Shellfish Poisoning : Toxic Syndromes

Scombroid Fish Poisoning

Scombroid poisoning is the name given to the histamine-like reaction that occasionally results from the ingestion of improperly cooled and stored tuna and related species in the family Scombridae. These dark-meat fish include the skipjack tuna ( Euthynnus pelamis ), the bonito ( Sarda sarda ), the mackerel ( Scomber scombrus ), and the albacore ( Thunnus alalunga ). A nonscombroid fish, mahi-mahi ( Coryphaena hippurus ), can also become toxic and is actually a commonly implicated fish in scombroid outbreaks in the United States. The Centers for Disease Control and Prevention reported two outbreaks of scombroid fish poisoning in late 2006, one in Louisiana and one in Tennessee. Both outbreaks were associated with tuna steaks imported from Indonesia and Vietnam, but consumed in Louisiana and Tennessee, respectively.

Fish become toxic after being caught, when inadequate cooling during transport and storage allows for bacterial proliferation. These bacteria (primarily Morganella morganii but also other bacteria such as Escherichia , Proteus , Salmonella , and Shigella species) degrade histidine present in the musculature of the fish to heat-stable histamine and a histamine-like substance termed saurine. Studies suggest that most symptoms are due to saurine, as histamine when given orally is poorly absorbed and chemically inactivated in the gastrointestinal tract. An exception may occur in patients treated with isoniazid for tuberculosis, as this medication inhibits histaminase in the gut and may make patients more susceptible to the histamine contained in scombrotoxic fish, thus accentuating the symptoms and signs of scombroid poisoning.

Scombrotoxic fish usually appear normal, but toxicity should be suspected if the fish tastes “peppery or sharp.” Within 30 minutes of ingestion of a toxic fish, a systemic histamine-like reaction occurs . Symptoms and signs include headache, flushing, a burning or peppery taste in the mouth, abdominal cramps with nausea, vomiting, diarrhea, tachycardia, dry mouth, and occasionally urticaria, angioedema, and bronchospasm. Symptoms are transient, rarely lasting over 8-12 hours, and deaths are unusual. Diagnosis is clinical but can be confirmed by measuring the histamine content of the suspected fish, which is generally 20 mg/100 g of fish muscle, or higher (normal histamine content is <1 mg/100 g of fish muscle). Treatment consists of forced emesis and antihistamines. In addition to diphenhydramine (Benadryl), treatment with histamine-2 antagonists such as cimetidine (300 mg intravenous [IV]) or ranitidine (50 mg IV) may provide symptomatic relief. If symptoms are severe, the patient may require IV fluids, antiinflammatory steroids, aminophylline, and epinephrine as used for anaphylaxis-like reactions.

Prevention consists of storing the fish at less than 40° F (4.4° C) at all times between catching and consumption, according to food-safety recommendations.

Ciguatera Fish Poisoning

Ciguatera poisoning presents with acute gastrointestinal and neurologic symptoms following the ingestion of normally edible reef fish that contain ciguatoxins produced by the unicellular marine dinoflagellate Gambierdiscus toxicus . Most outbreaks occur in the Caribbean, the Indo-Pacific islands, and the Indian Ocean between 35° North and 35° South latitude. Although more than 425 species of fish are known to be occasionally toxic, the more commonly implicated fish include the barracuda (Sphyraenidae), red snapper ( Lutjanus bohar ), grouper, amberjack ( Seriola dumerili ), sea bass (Serranidae), surgeonfish (Acanthuridae), and moray eel (Muraenidae). Previously, ciguatera poisoning was rarely reported outside local communities within the endemic tropical latitudes; however, increasing numbers of cases are being seen in nontropical countries as the number of international tourists grows each year, and unwary travelers who ingested contaminated fish in endemic areas return home with persistent symptoms. Ciguatera poisoning has become a world health issue as reef fish caught in ciguatera-endemic areas are exported to distant non-endemic areas.

Ciguatoxin (gambiertoxin) is a nonprotein polyether toxin with water-soluble and lipid-soluble fractions. The toxins and their metabolites are accumulated in the musculature, liver, and viscera of herbivorous fish and are concentrated in the food chain when carnivorous fish feed on the smaller herbivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. Increasing polarity of the toxin is associated with increased toxicity, and humans are exposed at the end of the food chain.

The main Pacific ciguatoxin (P-CTX-1) causes ciguatera poisoning at levels of 0.1 mcg/kg or higher in the flesh of carnivorous fish, whereas the main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxin induces partial membrane depolarization by enhancing sodium ion permeability in voltage-dependent sodium channels in nerve cell membranes. A recent report suggests that the ciguatoxins and brevetoxin (involved in neurotoxic shellfish poisoning) may have a potent effect on TRPV1 channels, modulating thermal and pain sensation.

Ciguatoxins are not affected by heating, freezing, or drying, and toxic fish have normal taste, texture, and odor. Symptoms develop 2-6 hours following ingestion of the fish and last about 1 week but occasionally can extend for months or even years. Typically, patients develop gastrointestinal symptoms such as nausea, watery diarrhea, abdominal cramps, or vomiting. Persistent bradycardia lasting several days has also been reported. Distal paresthesias are common, and the teeth may feel numb or loose. A majority of victims note an unusual hot-cold sensory reversal, in which cold objects “burn” when handled. Asthenia and arthralgias are frequent, and 10-45% of patients develop pruritus, usually 1-3 days after fish ingestion. Erythematous skin rashes that may blister or desquamate can occur in up to 20% of patients. In severe instances, ataxia, paresis, paralysis, or transient blindness occurs, often in association with sinus bradycardia and hypotension. Deaths are generally the result of respiratory depression, coma, and convulsions.

Diagnosis is made clinically but can be verified by assaying for the toxin in the implicated fish, using a bioassay (mouse, cat, mongoose, or brine shrimp), an enzyme-linked immunosorbent assay, or a radioimmunoassay.

Treatment is supportive and consists of forced emesis, IV fluids if volume is depleted, and respiratory support if indicated. IV mannitol (1 gm/kg) was reported to ameliorate neurologic symptoms when given acutely, but subsequent studies did not confirm its efficacy. Other drugs that have been anecdotally reported to give symptomatic relief are amitriptyline (50 mg/day), tocainide (400 mg three times a day), and nifedipine (10 mg three times a day). Another published report described successful treatment of ciguatera poisoning symptoms with gabapentin, a drug structurally related to gamma-aminobutyric acid and usually employed as an antiepileptic or for treatment of chronic pain. Treatment with gabapentin, 400 mg orally three times daily for up to 5 weeks, was reported to relieve neurologic symptoms, pruritus, and sharp, shooting pains in the legs associated with ciguatera poisoning, even though treatment was initiated 1 month after the onset of symptoms.