AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Ciguatera poisoning is the most common nonbacterial, fish-borne poisoning in the United States. It is caused by consumption of reef fish that feed on certain dinoflagellates (ie, algae) associated with coral reef systems. At least 5 types of ciguatoxin have been identified and are noted to accumulate in larger and older fish higher up the food chain. Ciguatera poisoning has been a significant concern in tropical areas for centuries and generally is believed to be confined to coral reef fish in water between the latitudes of 35 degrees north and 35 degrees south. In the modern era of world travel and rapid transportation, many warm-water fish are available commercially in markets throughout the world, and cases of ciguatera poisoning may be seen in any location.

Pathophysiology

Gambierdiscus toxicus is the dinoflagellate most notably responsible for production of ciguatoxin, although other species have been identified more recently. More than 400 species of fish have been implicated in ciguatera poisoning, starting with herbivores and then climbing up the food chain to the larger carnivorous fish.

Species of fish most frequently implicated include groupers, amberjack, red snappers, eel, sea bass, barracuda, and Spanish mackerel. Fish larger than 2 kg contain significant amounts of toxin and readily produce toxic effects when ingested. Although not completely reliable, an immunoassay and a mouse biologic assay are available for detection of ciguatoxin in affected fish. Ciguatoxin and other similar toxins are heat stable and lipid soluble; they are unaffected by temperature, gastric acid, or cooking method. Presence of toxin does not affect odor, color, or taste of the fish. Recently, chemists have been successful in synthesizing specific ciguatoxins, ensuring a practical supply will be available for future biological applications.

Frequency

United States

Most ciguatera outbreaks in the United States occur in Hawaii and Florida, although tourists may develop symptoms after returning home. Global marketing of tropical fish has been responsible for sporadic cases reported across the United States mainland.

International

Annually, an estimated 50,000 cases of ciguatera poisoning occur worldwide; however, this poisoning is difficult to track and is thought to be underreported. Ciguatera poisoning is endemic in Australia, the Caribbean, and the South Pacific islands. No doubt exists that ciguatera has had a substantial economic impact on many of the Third World countries where it is endemic.

Mortality/Morbidity

Ciguatera poisoning seldom is lethal. Typical mortality rate is 0.1%, although rates as high as 20% have been reported. Death usually is attributed to cardiovascular depression, respiratory paralysis, or hypovolemic shock.

Race

Several reports note that patients of similar ethnic backgrounds tend to share common symptom groupings.

Age

Children appear to be affected more severely and are involved more often in life-threatening cases.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

Currently, ciguatera poisoning is a clinical diagnosis based upon a constellation of symptoms temporally related to ingestion of suspect fish products. Onset of symptoms may be within 15 minutes or as late as 24 hours (rarely) after ingestion of the toxin. Generally, symptoms are noted within 6-12 hours after ingestion of tropical reef fish. Symptoms increase in frequency and severity over the subsequent 4-6 hours. Reported symptoms are numerous but commonly affect 3 major organ systems: GI, neurologic, and cardiovascular.

• GI symptoms often are the first to appear, may last 1-2 days, and include the following:
• • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
• Neurologic symptoms usually are multiple, varied, and, at times, bizarre. Symptoms may begin within a few hours to 3 days after the meal and can be persistent, lasting weeks to several months. Symptoms may include the following:
• • Lingual and circumoral paresthesias
  • Painful paresthesias of the extremities
  • Paradoxical temperature reversal (eg, cold objects feel hot and hot objects feel cold) (This is a classic reported finding; however, at least one study suggests that this perception is likely the result of the exaggerated and intense nerve depolarization and that gross temperature perception remains intact).
  • Dental pain (teeth feel loose)
  • Pruritus
  • Arthralgias
  • Myalgias
  • Weakness
  • Ataxia, vertigo
  • Respiratory paralysis
  • Coma
• Cardiovascular symptoms are less common but can be severe. They usually resolve within 2-5 days. Patients may experience weakness and dizziness from bradycardia and hypotension.
• Other features include dyspnea, sweating, salivation, chills, neck stiffness, and pruritus.

Physical

• Dehydration from GI losses is a common finding.
• Neurologic findings are extremely variable, from mild to life threatening.
• Cardiovascular findings include bradycardia and hypotension. Signs of shock may be observed. Hypotension results from the following:
• • Fluid loss

  • Bradycardia

  • Peripheral vasodilation

  • Myocardial depression

Causes

Ingestion of sufficient quantities of fish with accumulated ciguatoxin produces this syndrome.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

Botulism toxicity

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• All routine laboratory tests are nonspecific for ciguatera poisoning but may reflect volume depletion from fluid losses. Mild creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) elevations, if present, reflect muscle tissue breakdown.
• Currently, home products are available to detect ciguatoxin in fish at the time of preparation. Reliability of these products in the hands of the consumer has not been validated.
• Other companies are developing similar products for detection of ciguatoxin in human blood.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Emergency Department Care

• Treatment of ciguatera poisoning is largely supportive and symptom driven.
• GI decontamination with activated charcoal may be of value if performed within 3-4 hours of ingestion. Avoid syrup of ipecac because of its potential to worsen fluid losses. Orogastric lavage is not recommended; it is not of proven benefit for ciguatera poisoning, and risks of this procedure are likely to outweigh benefits.
• Antiemetics may control nausea and vomiting.
• Cool showers and antihistamines have been recommended to relieve pruritus.
• Manage hypotension with volume replacement. Pressor agents rarely are needed.
• Bradyarrhythmias respond well to atropine.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medications used to treat ciguatera poisoning include (1) neurologic agents, (2) serotonin-norepinephrine reuptake inhibitors, (3) antihistamines, (4) analgesics, (5) antipyretics, and (6) anti-inflammatories.

Drug Category: Diuretics, osmotic

These agents are used empirically to treat neurologic symptoms associated with ciguatera poisoning.

Drug Category: Serotonin/norepinephrine reuptake inhibitors

These agents have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin.

Drug Category: Analgesics

These agents are used symptomatically to provide pain relief.

Drug Name	Indomethacin (Indocin)
Description	Relieves myalgias and arthralgias.
Adult Dose	75 mg PO qd
Pediatric Dose	1.25-2.5 mg/kg/d PO divided tid/qid
Contraindications	Documented hypersensitivity; active GI bleed; previous peptic ulcer disease is a relative contraindication
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia)

Drug Category: Antihistamines

These agents are used to reduce pruritus (itching).

Drug Name	Diphenhydramine (Benadryl, Benylin)
Description	For relief of symptoms caused by release of histamine in pruritus.
Adult Dose	25-50 mg PO/IV/IM q4-6h
Pediatric Dose	5 mg/kg/d divided q4-6h
Contraindications	Documented hypersensitivity
Interactions	Potentiates effect of CNS depressants; because of alcohol content, do not give syrup form to patient taking medications that can cause disulfiramlike reactions
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Avoid in first trimester; unsafe when breastfeeding; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Drug Name	Hydroxyzine (Atarax, Vistaril)
Description	Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. Has antipruritic effects.
Adult Dose	0.5-1 mg/kg or 25-100 mg PO/IM qd/qid
Pediatric Dose	Not recommended
Contraindications	Documented hypersensitivity
Interactions	Alcohol or other CNS depressants may cause CNS depression
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid when breastfeeding; associated with clinical exacerbations of porphyria (may not be safe for porphyric patients); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Outpatient Care

• During the recovery period, victims of ciguatera poisoning should avoid ingesting any of the following, which cause an exacerbation of symptoms:
• • Any fish products

  • Shellfish products

  • Alcoholic beverages

  • Nuts

  • Nut oils

• Opiates and barbiturates also may exacerbate symptoms and are not recommended.

Deterrence/Prevention

• Avoiding consumption of tropical reef fish is the only true method of prevention. Although this method is not practical in all circumstances, the following can decrease the incidence of ciguatoxin poisoning:
• • Avoiding ingestion of fish larger than 2-3 kg that are at the top of the food chain

  • Avoiding all visceral organ and gonad meat (where ciguatoxin is concentrated)

Prognosis

• The prognosis is excellent. A recent small longitudinal cohort study from Miami revealed that all 12 patients were back to baseline on all neuropsychological studies by 6 months.¹

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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7. Fleming LE, Baden DG, Ayyar RA, Bean JA, Blythe DG, Shrank K, et al. A pilot study of a new ELISA test for ciguatoxin in humans. Bull Soc Pathol Exot. 1992;85(5 Pt 2):508-9. [Medline].
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9. Gopalakrishnakone P, Tan CK. Clinical features on 12,890 cases of ciguatera (fish poisoning) French Polynesia. Proceedings: First Asia-Pacific Congress on Animal, Plant and Microbial Toxins. 1987;June 24-27:372-385.
10. Habermehl GG, Krebs HC, Rasoanaivo P, Ramialiharisoa A. Severe ciguatera poisoning in Madagascar: a case report. Toxicon. Dec 1994;32(12):1539-42. [Medline].
11. Inoue M, Miyazaki K, Uehara H, Maruyama M, Hirama M. First- and second-generation total synthesis of ciguatoxin CTX3C. Proc Natl Acad Sci U S A. Aug 17 2004;101(33):12013-8. [Medline].
12. Lewis RJ. The changing face of ciguatera. Toxicon. Jan 2001;39(1):97-106. [Medline].
13. Mines D, Stahmer S, Shepherd SM. Poisonings: food, fish, shellfish. Emerg Med Clin North Am. Feb 1997;15(1):157-77. [Medline].
14. Morris PD, Campbell DS, Freeman JI. Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters. South Med J. Apr 1990;83(4):379-82. [Medline].
15. Park DL, Gamboa PM, Goldsmith CH. Rapid facile solid-phase immunobead assay for screening ciguatoxic fish in the market place. Bull Soc Pathol Exot. 1992;85(5 Pt 2):504-7. [Medline].
16. Pearn J. Neurology of ciguatera. J Neurol Neurosurg Psychiatry. Jan 2001;70(1):4-8. [Medline].
17. Pottier I, Vernoux JP, Lewis RJ. Ciguatera fish poisoning in the Caribbean islands and Western Atlantic. Rev Environ Contam Toxicol. 2001;168:99-141. [Medline].
18. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy. Neurology. Mar 2002;58(6):873-80. [Medline].
19. Swift AE, Swift TR. Ciguatera. J Toxicol Clin Toxicol. 1993;31(1):1-29. [Medline].
20. Ting JY, Brown AF. Ciguatera poisoning: a global issue with common management problems. Eur J Emerg Med. Dec 2001;8(4):295-300. [Medline].

Article Last Updated: Jun 7, 2007