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A brief case report and review of ciguatera poisoning
Wilderness and Environmental Medicine, 12, 263 269 (2001)
CASE REPORT
A brief case report and review of ciguatera poisoning DAVID JOHN FARSTAD, MD; TONY CHOW, MD From the Department of Emergency Medicine, United Medical Center, Cheyenne, WY (Dr Farstad), and the Department of Emergency Medicine, Loma Linda University, Loma Linda, CA (Dr Chow).
Although ciguatera fish poisoning is generally a mild, self-limited disease, both life-threatening acute reactions and troublesome chronic symptoms can occur. Because ciguatera has been largely confined to tropical locations, a relative lack of recognition exists among many US physicians. As access to tropical locations has increased, so has the distribution of ciguatera. Herein, we present a case report and review the current literature on ciguatera. Key words: ciguatera, ciguatoxin
Introduction Ciguatera poisoning is a fishborne illness prevalent in the tropics. Although most cases occur in Hawaii and Florida, it is the predominant nonbacterial fish poisoning in the United States.1,2 The prevalence of ciguatera may be underestimated because mild cases in endemic areas are probably rarely reported.3,4 Maritime history is filled with descriptions of ciguatera-like illness. Sixteenth-century historian Peter Martyr described ‘‘strange maladies’’ affecting his party after consuming fish caught in the West Indies, and Captain Cook attributed scorching heat on the skin to toxic fish at New Hebrides.5,6 Carnivorous reef fish are generally responsible for ciguatera outbreaks; in fact, barracuda are so prone to toxicity that their sale is prohibited in South Florida.7,8 On certain island communities where fish is the staple diet, ciguatera poisoning continues to be a tremendous socioeconomic problem.9 Although implicated fish typically originate between 35⬚N and 35⬚S latitude, sporadic poisonings are reported from fish caught outside this range.10,11 Worldwide distribution of tropical seafood has introduced potentially toxic fish to consumers in all climate zones. Defining ciguatera in terms of a small reliable group of symptoms is difficult. Ciguatera’s clinical toxicity is related to a variety of factors including age, sensitization, and regional toxin differences. Not only does the toxin (ciguatoxin [CTX]) exist in different chemical forms with varying clinical consequences, but there also Corresponding author: David Farstad, MD, 803 Deerbrooke Trail, Cheyenne, WY 82009 (e-mail: [email protected]).
exist other distinct toxins found in the same ecosystems that can be confused with, or contribute to, the complex array of symptoms we associate with ciguatera. Cases A previously healthy 34-year-old woman and a 40-yearold man became ill within 6 hours of eating barracuda they caught in turbid water near Cancun, Mexico. Both parties experienced vomiting, abdominal pain, and profuse watery diarrhea that abated within 12 hours. The couple returned home feeling weak and fatigued. Within several days, both patients noticed bizarre facial and extremity paresthesias, as well as the peculiar sensation that cold foods seemed hot, and hot drinks tasted ice cold. The woman complained of swollen glands in her neck and a sore throat, and she described her overall symptoms as mild. The man was more seriously affected, complaining of headaches, malaise, and debilitating burning and numbness in his hands and feet. When exercising, the man experienced unbearable pruritus, and during ejaculation, he described severe pubic pain. Neither victim described a history of fever or rash, and each stated the sensory symptoms were unlike anything they had experienced. Each patient was examined by several physicians during the 2 weeks following the onset of neurologic symptoms. The only remarkable objective finding in either patient was a tender submandibular lymph node in the woman. Both patients were found to have normal cranial nerve exams, and no objective abnormal sensory findings with one exception—the continued perception that
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Table 1. Partial list of fish associated with ciguatera* Species
Distribution
Lined surgeonfish (Acanthurus lineatus) Bonefish (Albula vulpes) Gray triggerfish (Balistes carolinensis) Saucereye porgy (Calamus calamus) Horse-eye jack (Caranx latus) Whitetip shark (Carcharhinus longimanus) Humphead wrasse (Cheilinus undulatus) Heavybeak parrotfish (Chlorurs gibbus) Red grouper (Epinephelus morio) Giant moray (Gymnothorax javanicus) Hogfish (Lachnolaimus maximus) Northern red snapper (Lutjanus campechanus) Tarpon (Megalops atlanticus) Narrowhead gray mullet (Mugil capurrii) Yellowtail snapper (Ocyurus chrysurus) Spotted coral grouper (Plectropomus maculatus) Blue parrotfish (Scarus coeruleus) Spanish mackerel (Scomberomorus maculatus) Lesser amberjack (Seriola fasciata) Great barracuda (Sphyraena barracuda) Chinamanfish (Symphorus nematophorus) Swordfish (Xiphias gladius)
Indo-Pacific Worldwide in warm seas Atlantic, Gulf of Mexico Western Atlantic Atlantic Worldwide Indo-Pacific Indo-Pacific Western Atlantic Indo-Pacific Western Atlantic Western Atlantic, Gulf of Mexico Eastern Atlantic East Central Atlantic Western Atlantic Western Pacific Western Atlantic Western Atlantic Western Atlantic Indo-Pacific, Western Atlantic Western Pacific Atlantic, Indo-Pacific, Mediterranean
*Adapted from Froese R, Pauly D, eds. Fishbase. Worldwide Web Electric Publication. 2001 www.fishbase.org.
cold objects felt hot, and likewise hot objects felt cold. Peripheral motor strength was normal as were upper motor neuron findings, Rhomberg, and gait. Routine laboratory tests were unremarkable. The woman’s mononucleosis and Group A streptococcus screens were negative. Five weeks after the onset of symptoms, the diagnosis of ciguatera was made, and since both parties were dramatically improving, no treatments were prescribed. Ten weeks after eating the barracuda, both patients were symptom free. Discussion EPIDEMIOLOGY AND TOXICOLOGY OF CIGUATERA Ciguatera poisoning is the most common illness related to finfish consumption worldwide.1,12 Surface microalgae (dinoflagellates) attached to biodetritus and macroalgae on coral reefs are associated with the causative toxins.12 Certain strains of Gambierdicus toxicus and Ostreopsis lenticularis produce toxins that are modified in the stomach of fish.13 Bacteria are involved in not only the proliferation of causative dinoflagellates, but they also appear to be symbiotic in toxin production.3 Dinoflagellates are consumed by small herbivores, which are
in turn ingested by the carnivorous reef dwelling and semipelagic fish species predominantly implicated in human poisoning (Table 1). Each geographic area possesses species prone to toxicity; for instance, barracuda, grouper, and snapper species are often involved in the Caribbean. The toxin is concentrated in the viscera (especially the liver, brain, and gonads), and although certain species appear resistant, the toxin can presumably reach levels lethal to some host fish.14 Toxic fish populations rise when coral reefs are altered by tidal waves, earthquakes, hurricanes, and dredging.10 Wave damage on the windward side of islands enhances dinoflagellate populations, and atypical weather patterns such as El Nin˜o may be associated with ciguatera outbreaks.10 A profuse growth of microalgae is also stimulated when nitrogen- and phosphorus-rich pollutants, as well as runoff from lacteric soils, enter coastal water.1,15,16 Plankton overgrowth turns water a variety of turbid colors in what is referred to as a ‘‘red tide.’’ Numerous phytoplankton species cause red tides, only some of which produce toxins.5 Neurotropic shellfish poisoning and paralytic shellfish poisoning occur during red tides, but ciguatera outbreaks may be delayed as the toxin passes up the food chain. Ciguatoxin comprises an extremely toxic group of
Ciguatera poisoning polycyclic ethers characterized by different clinical expressions.2,13,17 Pacific ciguatoxin is chemically distinct from Caribbean forms.14 Relative levels of different ciguatoxins are observed in different fish species in the same ecosystem, and preferential expression is based on the biochemical environment of the fish’s digestive tract.14 Ciguatoxin is colorless, odorless, lipid soluble, heat stable, not affected by freezing, and does not alter the taste or texture of fish.1 Ciguatoxin binds to Site 5 on voltage-gated sodium channels, affecting them in an unconventional manner by competitively inhibiting calcium’s membrane-polarizing influence on passive sodium channels, causing intracellular levels of sodium and calcium to increase.13 The persistent opening of sodium channels both slows and reduces the amplitude of nerve impulses.18 The result is membrane depolarization followed by nerve blockade. Small structural variations in ciguatoxin underlie variable affinity for sodium channels in different tissue.19 In Schwann cells, ciguatoxin increases intracellular sodium concentrations, causing water influx, nodal swelling, and inhibition of neurotransmitter uptake.13,20 Scaritoxin, sometimes identified as a ciguatoxin, blocks sodium channels and is therefore a notable exception to the above model.21 Scaritoxin causes two reported clinical phases; the first resembles ciguatera poisoning, followed by delayed ataxia.14 Evidence from animal studies shows the effects of ciguatoxin are both host and dose dependent. Secretory diarrhea may involve the ability of ciguatoxin to increase intracellular calcium, which acts as a second messenger disrupting ion exchange.13,17 In guinea pigs, adrenergicand cholinergic-mediated inotropic effects, as well as a direct positive inotropic effect, have been observed.13,17 Action on the human heart appears to be related primarily to indirect effects on intrinsic nerves, rather than a direct effect on myocardial cells.19 The heterogeneous effects of ciguatoxin in different species speak to the limitations of animal models. CLINICAL PRESENTATION OF CIGUATERA Within 24 hours of ingesting CTX, 3 groups of symptoms emerge: alimentary, neurological, and cardiovascular. Not all persons become symptomatic, and the severity of symptoms is dose dependent.22 Differences in clinical response are related to individual susceptibility, prior exposure, and sensitization.12 Immune sensitization may explain why some exposed patients have a persistent intolerance for other polycyclic ethers.23 Other factors may explain lethal reactions; for instance, animal studies suggest high toxin loads may induce phrenic nerve paralysis.24 Ingesting the head or liver of contaminated fish may be particularly dangerous, as the toxin
265 is concentrated in those body parts.24 Severe toxicity may also be related to consumption of more lethal coexistent poisons, recognized or unrecognized. Mortality rates are reported as high as 5% but are probably in the range of 0.1%.12,13 A report from Madagascar describes a 20% mortality among 500 persons ingesting shark meat, but the same incident has also been attributed to various toxins.3,25 Predominant symptoms in Madagascar included paresthesias, abdominal pain, pruritus, pulmonary edema, and coma, with a conspicuous lack of diarrhea. This incident is not classical for any known ichthyosarcotoxism, but many symptoms point to ciguatera. Gastrointestinal symptoms, especially nonbloody, watery diarrhea, classically appear within 2 to 12 hours of toxin ingestion and dominate the early course of ciguatera, typically ending within 2 days.16 Caribbean cases of ciguatera cause more alimentary symptoms, whereas neurologic symptoms are more pronounced in the Pacific.8 Cardiovascular symptoms occur early and often persist beyond the gastrointestinal phase but, unlike neurological symptoms, abate within 1 week.8 Ten percent to 15% of exposures result in hypotension and bradycardia, the latter attributed to atrioventricular block.1,26 Bradycardia and hypotension are more frequent in persons ingesting larger fish.22 Electrocardiogram changes, including T-wave abnormalities, are common but not understood.19 Neurological symptoms characterize ciguatera and variably develop from immediately up to several weeks after the intestinal illness. Burning paresthesias on the face and extremities occur in 36% to 89%, depending on the region.16 Temperature reversals on buccal and acral membranes are specific but not pathognomonic for ciguatera, also occurring after exposure to certain brevitoxins.8,11 Bagnis et al26 reported that 88% of cases in the South Pacific resulted in paradoxical dysesthesias. Temperature reversal is described more specifically as a ‘‘dry ice,’’ ‘‘burning,’’ or an ‘‘electric shock’’ sensation, and studies suggest abnormal sensation is related to activity in peripheral C-polymodal nociceptor fibers, rather than alterations in gross temperature sensation.27 Severe pruritus occurred in 5% of cases in Fiji and 89% in French Polynesia and appears to be exacerbated by exercise or ingestion of alcohol.6,16 In New Caledonia, ciguatera is so commonly associated with pruritus, it is referred to as ‘‘the itch.’’13 Ascending paralysis and cranial nerve deficits rarely occur and are more common in the South Pacific. Ataxia can be prolonged and is presumed to be a result of scaritoxin.14 The seemingly endless list of symptoms in ciguatera likely stems from both the variable expression of toxins in fish and from confusion with similar marine poison-
266 ings (Table 2). Nonspecific, often macular, rashes occur in many South Pacific victims.7 Mood disorders and hallucinations may precipitate a psychiatric referral.8,28,29 Several cases of painful ejaculation followed by female partners complaining of dyspareunia are reported, and dysuria is common in the Caribbean.12,30 CTX can cross the placenta, and children born to mothers affected late in pregnancy have exhibited abnormal prenatal movement and temporary cranial nerve deficits.2,12 Transmission through milk is suspected, and hyperesthesia of the nipples is reported in breast-feeding mothers.13 Although no teratogenic effects of ciguatera have been described, premature labor and miscarriage are reported.13 DIAGNOSTICS AND TREATMENT Ciguatera is solely a clinical diagnosis with no specific physical findings. Laboratory data are nonconfirmatory and, with the exception of occasional small increases in liver enzymes, are usually normal.6,24 Resolution of symptoms typically occurs within 2 weeks, with a mean duration of 8.5 days, although some cases persist for months or years.18,31 Paresthesias of the face and extremities generally account for protracted symptoms. Ethnic and age variations exist, and Filipino and Chinese persons, as well as children and elderly individuals, appear to have worse symptoms.13,16 Like similar marine polycyclic ether poisonings, current therapy for ciguatera is primarily supportive. Gastric emptying, activated charcoal, and catharsis are recommended in the acute phase.5 Mannitol appears to reverse acute neurologic and gastrointestinal symptoms, although its use is mostly anecdotal.1,19 Palafox et al32 noted immediate reversal of 2 patients in a coma and 1 in shock with mannitol infusion. Improvement was noted by Pearn et al33 in 8 of 12 patients of variable severity after mannitol was given. Several anecdotal reports have suggested mannitol may work well after the acute phase of the illness.28,34 Mannitol is believed to reverse the effects of CTX by osmotically reducing sodium entry and causing an efflux of water from cells, and it may also act as a scavenger for hydroxyl radicals on the ciguatera molecule.13 During life-threatening reactions, dopamine and atropine will reverse hypotension and bradycardia, respectively. Acetaminophen, nonsteroidal anti-inflammatory drugs, and ascorbic acid relieve chronic neurological symptoms.1,23 Amitriptyline retrospectively diminished paresthesias when given to patients thought to have depression and is theorized to alter the response at the sodium channel.12,13 Pyridoxine, diazepam, nifedipine, Vitamin B, pralidoxime, protamide, fluoxetine, and corticosteroids have all been used with variable success.24 A
Farstad and Chow Table 2. Symptoms of ciguatera Gastrointestinal (common/early onset/lasts 1 to 2 days) Nausea Vomiting Diarrhea Abdominal pain Hypersalivation Cardiovascular (uncommon/early onset/persists up to 1 week) Hypotension Bradycardia Tachycardia Other (Variable occurrence and onset) Chills Perspiration Fever Loss of hair and nails Conjunctivitis Acne Skin rash Malaise Neurologic (common/late onset*/prolonged symptoms) Mental status Delirium Coma Confusion Depression Motor Ataxia Spasticity Respiratory arrest Opthalmoplegia Seizures Paresis Diminished reflexes Weakness Tonic contractions Sensory Paresthesias Pardoxical dysesthesias Asthenia Headache Myalgia Dental pain Photophobia Blindness Vertigo Arthralgias Metallic taste Blurred vision Pruritus Dyspareunia Painful ejaculation Dysuria *Neurologic symptoms can occur early in the disease course, but they classically follow gastrointestinal and cardiovascular symptoms.
Ciguatera poisoning recent report links improvement in several patients to gabapentin, a drug occasionally used to treat neuropathic pain.35 Lidocaine theoretically offers advantages in cardiovascular toxicity because it blocks nerve conduction by decreasing membrane permeability of sodium ions, and it may block the ciguatoxin-modified sodium channel.17,24 Alcohol and vigorous exercise seem to exacerbate neurotropic symptoms and should be avoided for at least several months.7,14 For unknown reasons, nonreef fish and shellfish products can precipitate the reappearance of neurotoxic symptoms.13 Ciguatera patients are described as being intolerant of cyclic ethers such as morphine sulfate, and paraldehyde.23 Many other substances have been hypothesized to cause the reemergence of symptoms; however, the occurrence of such is rare.13,23 Exposure to low levels of ciguatoxin may precipitate an exacerbation in some preexposed individuals; thus, reef fish with otherwise subthreshold toxin levels might cause symptoms in this group.12 Numerous practices have been used to determine if fish are toxic, none of which is adequately sensitive. Some cultures feed suspect fish to pets and observe them for ill effects. One man was said to repeatedly test suspect fish by feeding them to his mother-in-law.13 Animal and immunoassays have traditionally been considered nonspecific, although reverse-phase high-performance liquid chromatography/mass spectrometry is offering new promise.36 Related marine toxins TOXINS ASSOCIATED WITH CIGUATERA OUTBREAKS Ciguatoxins are considered the primary toxins in ciguatera poisoning, but maitotoxin, palytoxin, okadaic acid, and other marine toxins have been recovered from ciguatoxic fish. Most of these toxins belong to a group of compounds referred to as ‘‘polycyclic ethers.’’4 Maitotoxin is isolated from G toxicus cultures, but its role in ciguatera poisoning remains uncertain.14 Maitotoxin is a potent water-soluble toxin with hemolytic properties and profound hypotensive effects after in vitro injection; however, its low oral potency may limit its role in human poisonings.14,23 Maitotoxin is primarily concentrated in the fish’s liver and may play a role in severe reactions occurring when the organs of fish are consumed. Palytoxins are another potent group of polyether toxins that may play a part, or be confused with, ciguatera.14 In addition to crabs, fish, and marine worms, palytoxin has been isolated in ciguatoxic fish, as well as G toxicus and O lenticularis cultures.3 Ingestion of paly-
267 toxin results in severe headaches, paresthesias, skin irritation, paralysis, and intense tonic muscle contractions resulting in rhabdomyolysis.37 Palytoxin is reported to be a potent vasoconstrictor that can cause organ anoxia and ischemia.3 Ciguatera does not classically produce rhabdomyolysis or organ ischemia; thus, it is reasonable to consider a coexistent toxin such as palytoxin when these findings are combined with a usual ciguatera presentation. Finally, okadaic acid is one of a class of marine polyether toxins including dinophysistoxins and pectinotoxins causing secretory diarrhea in humans.3 Dinoflagellates containing okadaic acid have been linked to ciguatera outbreaks, and the presence of the toxin in ciguatoxic fish alludes to a possible connection to ciguatera poisoning.14 TOXINS NOT ASSOCIATED WITH CIGUATERA OUTBREAKS Like ciguatoxin, saxitoxin, tetrodotoxin, and brevetoxins are marine toxins specific to voltage-gated sodium channels; however, unlike okadaic acid and maitotoxin, an association with ciguatera outbreaks has not been described. We briefly mention these toxins to assist in developing a differential for these related marine poisonings. Saxitoxin is one of several dinoflagellate-associated toxins responsible for paralytic shellfish poisoning.3 Bivalve mollusks, fish, shrimp, and lobsters are known transvectors of saxitoxin poisoning, and although one mussel may contain as much as 50 mg, as little as 0.1 mg may be lethal.1 Paresthesias begin within 30 minutes of saxitoxin ingestion and progress to vomiting, muscle paralysis, and respiratory arrest within hours. Tetrodotoxin is a notorious marine poison and is found in many animals including puffer fish, crabs, ocean sunfish, starfish, blue ringed octopus, and Central American frogs.1,2 Fugu, a puffer fish, is still a cause of food poisoning deaths in Japan. Paresthesias and an unusual floating sensation progress quickly to ascending muscle paralysis, seizures, and respiratory arrest. Direct action on vascular smooth muscle and inhibition of vasomotor nerves precipitate hypotension, and some victims experience bradycardia.5 If saxitoxin or tetrodotoxin ingestion is suspected, gastric lavage with 2% sodium bicarbonate has been suggested, as polycyclic ethers lose their stability in basic solutions. Brevitoxins produced by the red tide dinoflagellate Ptychodiscus brevis are implicated in neurotropic shellfish poisoning, and, despite the name, fish also serve as hosts. Brevitoxin poisoning is associated with mild cardiovascular and respiratory depression, paresthesias, local cutaneous irritation, and other neurologic dysfunc-
268 tion.38 The toxins are selectively lethal to fish and are presumably unable to concentrate to levels sufficient to cause severe human poisoning.14 Ciguatera poisoning is more likely to be confused with brevitoxin exposure than the syndromes caused by saxitoxin or tetrodotoxin. Summary Outbreaks of ciguatera are unpredictable. In Venezuela, 200 cases on a cruise ship resulted in several fatalities.4 An outbreak of cases in Southern California was tracked to grouper harvested off the coast of the Baja peninsula during an El Nin˜o year.10 Patients with unexplained neurologic symptoms or with any acute gastrointestinal illness should be questioned about recent fish consumption. Supportive care is typically all that is needed; however, acute life-threatening reactions and chronic debilitating symptoms do occur. Mannitol appears to be an effective antidote, although it remains unclear why. Immunoassays are being refined to screen both fish and humans. In light of recent advances in marine toxicology, defining ciguatera in terms of a distinct clinical syndrome is unrealistic. The disease presents as a montage of symptoms caused by a variety of toxins and is probably confused with other similar intoxicants. Considering the worldwide prevalence of ciguatera, it is startling how many physicians are unfamiliar with this disease. The diagnosis is usually suggested by the history, yet patients seeking care far from endemic areas are often misdiagnosed. The popularity of tropical vacations and the increased availability of exotic frozen fish may well increase the incidence of ciguatera in North America.
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9.
10.
11.
12. 13. 14.
15.
16. 17.
18.
19. 20.
References 1. Eastough J, Sheperd S. Infections and toxic syndromes from fish and shellfish consumption. Arch Intern Med. 1989;149:1735–1739. 2. Brown CK, Shepherd SM. Marine trauma, envenomations, and intoxications. Emerg Med Clin North Am. 1992;10: 401–403. 3. Tosteson TR. The diversity and origins of toxins in ciguatera fish poisoning. PR Health Sci J. 1995;14:117–129. 4. Doorenbos N. Ciguatera toxins: where do we go from here? In: Seafood Toxins. Washington, DC: American Chemical Society; 1984:69–73. 5. Sakamoto Y, Lockey RF, Krzanowski JJ. Shellfish and fish poisoning related to the toxic dinoflagellates. South Med J. 1987;80:866–870. 6. Broadbent G. Ciguatera. Aust Fam Physician. 1987;16: 127–128. 7. Hampton MT, Hampton AA. Ciguatera fish poisoning. J Am Acad Dermatol. 1989;20:510–511. 8. Geller RJ, Olson KR, Senecal PE. Ciguatera fish poisoning
21.
22.
23.
24. 25.
26.
in San Francisco, California, caused by imported barracuda. West J Med. 1991;155:639–642. Bagnes R, Spiegel A, Nguyen L, Plichart R. Public health, epidemiological and socioeconomic patterns of ciguatera in Tahiti. Proceedings of the Third International Conference on Ciguatera Fish Poisoning. 1992; Puerto Rico. Quebec, Canada: Polyscience Publications; 1992. Barton ED, Tanner P, Turchen SG, Tunget CL, Manoguerra A. Ciguatera fish poisoning—a southern California epidemic. West J Med. 1995;163:31–35. Morris PD, Campbell DS, Freeman JI. Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters. South Med J. 1990;83:379–381. Lange WR. Ciguatera fish poisoning. Am Fam Physician. 1994;50:579–584. Swift AEB, Swift TR. Ciguatera. J Toxicol Clin Toxicol. 1993;31:777–781. Lewis RJ, Holmes MJ. Origin and transfer of toxins involved in ciguatera. Comp Biochem Physiol. 1993;106C: 615–628. Rougerie F, Bagnis R. Bursts of ciguatera and endo-upwelling process on coral reef. Bull Soc Pathol Exot. 1992; 85:464–466. Glaziou P, Legrand AM. The epidemiology of ciguatera fish poisoning. Toxicon. 1993;32:863–873. Lewis RJ, Hoy AW. Comparative action of three major ciguatoxins on guinea-pig atria and ilea. Toxicon. 1993; 31:434–446. Cameron J, Flowers AE, Capra MF. Modification of the peripheral nerve disturbance in ciguatera poisoning in rats with lidocaine. Muscle Nerve. 1993;16:782–786. Lewis RJ, Hoy AW, Mcgiffin DC. Action of ciguatoxin on human atrial trabeculae. Toxicon. 1992;30:907–914. Benoit E, Juzans P, Legrand AM, Molgo J. Nodal swelling produced by ciguatoxin-induced selective activation of sodium channels in myelinated nerve fibers. Neuroscience. 1996;71:1121–1131. Satake M, Ishibashi Y, Legrand AM, Yasumoto T. Isolation and structure of ciguatoxin-A4, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdicus toxicus and parrot fish Scarus gibus. Biosci Biotechnol Biochem. 1996;60:2103–2105. Katz AR, Terrell-Perica S, Sasaki DM. Ciguatera on Kauai: investigation of factors associated with severity of illness. Am J Trop Med Hyg. 1993;49:448–454. Sims JK. A theoretical discourse on the pharmacology of toxic marine ingestions. Ann Emerg Med. 1987;16:1006– 1013. Schatz IJ. Ciguatera fish poisoning: a jet age peril. Hosp Pract. 1989;24:79–94. Boisier P, Ranaivoson G, Rasolafonirana N, Andriahefazafy R, Roux J. Fatal mass poisoning in Madagascar following ingestion of a shark (Carcharhinus leucas): clinical and epidemiological aspects and isolation of toxins. Toxicon. 1994;33:1359–1364. Bagnis R, Kuberski T, Laugier S. Clinical observations on
Ciguatera poisoning
27.
28.
29. 30.
31. 32.
33.
3009 cases of ciguatera (fish poisoning) in the South Pacific. Am J Trop Med Hyg. 1979;28:1067–. Cameron J, Capra MF. The basis of the paradoxical disturbance of temperature perception in ciguatera poisoning. J Toxicol Clin Toxicol. 1993;31:571–579. Fenner PJ, Lewis RJ, Williamson JA, Williams ML. A Queensland family with ciguatera after eating coral trout. Med J Aust. 1997;166:473–475. Lipkin KM. Ciguatera poisoning presenting as a psychiatric disorder. Arch Gen Psychiatry. 1989;46:384–385. Lange WR, Lipkin KM, Yang GC. Can ciguatera be a sexually transmitted disease? J Toxicol Clin Toxicol. 1989; 27:193–197. Hughes JM, Meison MH. Fish and shellfish poisoning. N Engl J Med. 1976;295:1117–1120. Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988;259:2740–2742. Pearn JH, Lewis RJ, Ruff T, Tait M, Quinn J. Ciguatera
269
34.
35.
36.
37. 38.
and mannitol: experience with a new treatment regimen. Med J Aust. 1989;151:77–80. Blythe DG, De Sylva DP, Fleming LE, Ayyar RA, Baden DG. Clinical experience with IV mannitol in the treatment of ciguatera fish poisoning. Bull Soc Pathol Exot. 1993; 85:425–426. Perez C, Vasquez PA, Penet CF. Treatment of ciguatera poisoning with gabapentin. [Letter]. N Engl J Med. 2001; 344:692–693. Lewis RJ, Jones A, Vernoux JP. HPLC/tandem electrospray mass spectrometry for the determination of sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish. Anal Chem. 1999;71:247–250. Lange WR. Puffer fish poisoning [Review]. Am Fam Physician. 1990;42:1029–1033. Bagnis R, Chanteau S, Chungue E. Origins of ciguatera fish poisoning—a new dinoflagellate, Gambierdicus toxicus Adachi and Fulcuyo, definitively involved as a causal agent. Toxicon. 1980;18:199–208.
CASE REPORT
A brief case report and review of ciguatera poisoning DAVID JOHN FARSTAD, MD; TONY CHOW, MD From the Department of Emergency Medicine, United Medical Center, Cheyenne, WY (Dr Farstad), and the Department of Emergency Medicine, Loma Linda University, Loma Linda, CA (Dr Chow).
Although ciguatera fish poisoning is generally a mild, self-limited disease, both life-threatening acute reactions and troublesome chronic symptoms can occur. Because ciguatera has been largely confined to tropical locations, a relative lack of recognition exists among many US physicians. As access to tropical locations has increased, so has the distribution of ciguatera. Herein, we present a case report and review the current literature on ciguatera. Key words: ciguatera, ciguatoxin
Introduction Ciguatera poisoning is a fishborne illness prevalent in the tropics. Although most cases occur in Hawaii and Florida, it is the predominant nonbacterial fish poisoning in the United States.1,2 The prevalence of ciguatera may be underestimated because mild cases in endemic areas are probably rarely reported.3,4 Maritime history is filled with descriptions of ciguatera-like illness. Sixteenth-century historian Peter Martyr described ‘‘strange maladies’’ affecting his party after consuming fish caught in the West Indies, and Captain Cook attributed scorching heat on the skin to toxic fish at New Hebrides.5,6 Carnivorous reef fish are generally responsible for ciguatera outbreaks; in fact, barracuda are so prone to toxicity that their sale is prohibited in South Florida.7,8 On certain island communities where fish is the staple diet, ciguatera poisoning continues to be a tremendous socioeconomic problem.9 Although implicated fish typically originate between 35⬚N and 35⬚S latitude, sporadic poisonings are reported from fish caught outside this range.10,11 Worldwide distribution of tropical seafood has introduced potentially toxic fish to consumers in all climate zones. Defining ciguatera in terms of a small reliable group of symptoms is difficult. Ciguatera’s clinical toxicity is related to a variety of factors including age, sensitization, and regional toxin differences. Not only does the toxin (ciguatoxin [CTX]) exist in different chemical forms with varying clinical consequences, but there also Corresponding author: David Farstad, MD, 803 Deerbrooke Trail, Cheyenne, WY 82009 (e-mail: [email protected]).
exist other distinct toxins found in the same ecosystems that can be confused with, or contribute to, the complex array of symptoms we associate with ciguatera. Cases A previously healthy 34-year-old woman and a 40-yearold man became ill within 6 hours of eating barracuda they caught in turbid water near Cancun, Mexico. Both parties experienced vomiting, abdominal pain, and profuse watery diarrhea that abated within 12 hours. The couple returned home feeling weak and fatigued. Within several days, both patients noticed bizarre facial and extremity paresthesias, as well as the peculiar sensation that cold foods seemed hot, and hot drinks tasted ice cold. The woman complained of swollen glands in her neck and a sore throat, and she described her overall symptoms as mild. The man was more seriously affected, complaining of headaches, malaise, and debilitating burning and numbness in his hands and feet. When exercising, the man experienced unbearable pruritus, and during ejaculation, he described severe pubic pain. Neither victim described a history of fever or rash, and each stated the sensory symptoms were unlike anything they had experienced. Each patient was examined by several physicians during the 2 weeks following the onset of neurologic symptoms. The only remarkable objective finding in either patient was a tender submandibular lymph node in the woman. Both patients were found to have normal cranial nerve exams, and no objective abnormal sensory findings with one exception—the continued perception that
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Table 1. Partial list of fish associated with ciguatera* Species
Distribution
Lined surgeonfish (Acanthurus lineatus) Bonefish (Albula vulpes) Gray triggerfish (Balistes carolinensis) Saucereye porgy (Calamus calamus) Horse-eye jack (Caranx latus) Whitetip shark (Carcharhinus longimanus) Humphead wrasse (Cheilinus undulatus) Heavybeak parrotfish (Chlorurs gibbus) Red grouper (Epinephelus morio) Giant moray (Gymnothorax javanicus) Hogfish (Lachnolaimus maximus) Northern red snapper (Lutjanus campechanus) Tarpon (Megalops atlanticus) Narrowhead gray mullet (Mugil capurrii) Yellowtail snapper (Ocyurus chrysurus) Spotted coral grouper (Plectropomus maculatus) Blue parrotfish (Scarus coeruleus) Spanish mackerel (Scomberomorus maculatus) Lesser amberjack (Seriola fasciata) Great barracuda (Sphyraena barracuda) Chinamanfish (Symphorus nematophorus) Swordfish (Xiphias gladius)
Indo-Pacific Worldwide in warm seas Atlantic, Gulf of Mexico Western Atlantic Atlantic Worldwide Indo-Pacific Indo-Pacific Western Atlantic Indo-Pacific Western Atlantic Western Atlantic, Gulf of Mexico Eastern Atlantic East Central Atlantic Western Atlantic Western Pacific Western Atlantic Western Atlantic Western Atlantic Indo-Pacific, Western Atlantic Western Pacific Atlantic, Indo-Pacific, Mediterranean
*Adapted from Froese R, Pauly D, eds. Fishbase. Worldwide Web Electric Publication. 2001 www.fishbase.org.
cold objects felt hot, and likewise hot objects felt cold. Peripheral motor strength was normal as were upper motor neuron findings, Rhomberg, and gait. Routine laboratory tests were unremarkable. The woman’s mononucleosis and Group A streptococcus screens were negative. Five weeks after the onset of symptoms, the diagnosis of ciguatera was made, and since both parties were dramatically improving, no treatments were prescribed. Ten weeks after eating the barracuda, both patients were symptom free. Discussion EPIDEMIOLOGY AND TOXICOLOGY OF CIGUATERA Ciguatera poisoning is the most common illness related to finfish consumption worldwide.1,12 Surface microalgae (dinoflagellates) attached to biodetritus and macroalgae on coral reefs are associated with the causative toxins.12 Certain strains of Gambierdicus toxicus and Ostreopsis lenticularis produce toxins that are modified in the stomach of fish.13 Bacteria are involved in not only the proliferation of causative dinoflagellates, but they also appear to be symbiotic in toxin production.3 Dinoflagellates are consumed by small herbivores, which are
in turn ingested by the carnivorous reef dwelling and semipelagic fish species predominantly implicated in human poisoning (Table 1). Each geographic area possesses species prone to toxicity; for instance, barracuda, grouper, and snapper species are often involved in the Caribbean. The toxin is concentrated in the viscera (especially the liver, brain, and gonads), and although certain species appear resistant, the toxin can presumably reach levels lethal to some host fish.14 Toxic fish populations rise when coral reefs are altered by tidal waves, earthquakes, hurricanes, and dredging.10 Wave damage on the windward side of islands enhances dinoflagellate populations, and atypical weather patterns such as El Nin˜o may be associated with ciguatera outbreaks.10 A profuse growth of microalgae is also stimulated when nitrogen- and phosphorus-rich pollutants, as well as runoff from lacteric soils, enter coastal water.1,15,16 Plankton overgrowth turns water a variety of turbid colors in what is referred to as a ‘‘red tide.’’ Numerous phytoplankton species cause red tides, only some of which produce toxins.5 Neurotropic shellfish poisoning and paralytic shellfish poisoning occur during red tides, but ciguatera outbreaks may be delayed as the toxin passes up the food chain. Ciguatoxin comprises an extremely toxic group of
Ciguatera poisoning polycyclic ethers characterized by different clinical expressions.2,13,17 Pacific ciguatoxin is chemically distinct from Caribbean forms.14 Relative levels of different ciguatoxins are observed in different fish species in the same ecosystem, and preferential expression is based on the biochemical environment of the fish’s digestive tract.14 Ciguatoxin is colorless, odorless, lipid soluble, heat stable, not affected by freezing, and does not alter the taste or texture of fish.1 Ciguatoxin binds to Site 5 on voltage-gated sodium channels, affecting them in an unconventional manner by competitively inhibiting calcium’s membrane-polarizing influence on passive sodium channels, causing intracellular levels of sodium and calcium to increase.13 The persistent opening of sodium channels both slows and reduces the amplitude of nerve impulses.18 The result is membrane depolarization followed by nerve blockade. Small structural variations in ciguatoxin underlie variable affinity for sodium channels in different tissue.19 In Schwann cells, ciguatoxin increases intracellular sodium concentrations, causing water influx, nodal swelling, and inhibition of neurotransmitter uptake.13,20 Scaritoxin, sometimes identified as a ciguatoxin, blocks sodium channels and is therefore a notable exception to the above model.21 Scaritoxin causes two reported clinical phases; the first resembles ciguatera poisoning, followed by delayed ataxia.14 Evidence from animal studies shows the effects of ciguatoxin are both host and dose dependent. Secretory diarrhea may involve the ability of ciguatoxin to increase intracellular calcium, which acts as a second messenger disrupting ion exchange.13,17 In guinea pigs, adrenergicand cholinergic-mediated inotropic effects, as well as a direct positive inotropic effect, have been observed.13,17 Action on the human heart appears to be related primarily to indirect effects on intrinsic nerves, rather than a direct effect on myocardial cells.19 The heterogeneous effects of ciguatoxin in different species speak to the limitations of animal models. CLINICAL PRESENTATION OF CIGUATERA Within 24 hours of ingesting CTX, 3 groups of symptoms emerge: alimentary, neurological, and cardiovascular. Not all persons become symptomatic, and the severity of symptoms is dose dependent.22 Differences in clinical response are related to individual susceptibility, prior exposure, and sensitization.12 Immune sensitization may explain why some exposed patients have a persistent intolerance for other polycyclic ethers.23 Other factors may explain lethal reactions; for instance, animal studies suggest high toxin loads may induce phrenic nerve paralysis.24 Ingesting the head or liver of contaminated fish may be particularly dangerous, as the toxin
265 is concentrated in those body parts.24 Severe toxicity may also be related to consumption of more lethal coexistent poisons, recognized or unrecognized. Mortality rates are reported as high as 5% but are probably in the range of 0.1%.12,13 A report from Madagascar describes a 20% mortality among 500 persons ingesting shark meat, but the same incident has also been attributed to various toxins.3,25 Predominant symptoms in Madagascar included paresthesias, abdominal pain, pruritus, pulmonary edema, and coma, with a conspicuous lack of diarrhea. This incident is not classical for any known ichthyosarcotoxism, but many symptoms point to ciguatera. Gastrointestinal symptoms, especially nonbloody, watery diarrhea, classically appear within 2 to 12 hours of toxin ingestion and dominate the early course of ciguatera, typically ending within 2 days.16 Caribbean cases of ciguatera cause more alimentary symptoms, whereas neurologic symptoms are more pronounced in the Pacific.8 Cardiovascular symptoms occur early and often persist beyond the gastrointestinal phase but, unlike neurological symptoms, abate within 1 week.8 Ten percent to 15% of exposures result in hypotension and bradycardia, the latter attributed to atrioventricular block.1,26 Bradycardia and hypotension are more frequent in persons ingesting larger fish.22 Electrocardiogram changes, including T-wave abnormalities, are common but not understood.19 Neurological symptoms characterize ciguatera and variably develop from immediately up to several weeks after the intestinal illness. Burning paresthesias on the face and extremities occur in 36% to 89%, depending on the region.16 Temperature reversals on buccal and acral membranes are specific but not pathognomonic for ciguatera, also occurring after exposure to certain brevitoxins.8,11 Bagnis et al26 reported that 88% of cases in the South Pacific resulted in paradoxical dysesthesias. Temperature reversal is described more specifically as a ‘‘dry ice,’’ ‘‘burning,’’ or an ‘‘electric shock’’ sensation, and studies suggest abnormal sensation is related to activity in peripheral C-polymodal nociceptor fibers, rather than alterations in gross temperature sensation.27 Severe pruritus occurred in 5% of cases in Fiji and 89% in French Polynesia and appears to be exacerbated by exercise or ingestion of alcohol.6,16 In New Caledonia, ciguatera is so commonly associated with pruritus, it is referred to as ‘‘the itch.’’13 Ascending paralysis and cranial nerve deficits rarely occur and are more common in the South Pacific. Ataxia can be prolonged and is presumed to be a result of scaritoxin.14 The seemingly endless list of symptoms in ciguatera likely stems from both the variable expression of toxins in fish and from confusion with similar marine poison-
266 ings (Table 2). Nonspecific, often macular, rashes occur in many South Pacific victims.7 Mood disorders and hallucinations may precipitate a psychiatric referral.8,28,29 Several cases of painful ejaculation followed by female partners complaining of dyspareunia are reported, and dysuria is common in the Caribbean.12,30 CTX can cross the placenta, and children born to mothers affected late in pregnancy have exhibited abnormal prenatal movement and temporary cranial nerve deficits.2,12 Transmission through milk is suspected, and hyperesthesia of the nipples is reported in breast-feeding mothers.13 Although no teratogenic effects of ciguatera have been described, premature labor and miscarriage are reported.13 DIAGNOSTICS AND TREATMENT Ciguatera is solely a clinical diagnosis with no specific physical findings. Laboratory data are nonconfirmatory and, with the exception of occasional small increases in liver enzymes, are usually normal.6,24 Resolution of symptoms typically occurs within 2 weeks, with a mean duration of 8.5 days, although some cases persist for months or years.18,31 Paresthesias of the face and extremities generally account for protracted symptoms. Ethnic and age variations exist, and Filipino and Chinese persons, as well as children and elderly individuals, appear to have worse symptoms.13,16 Like similar marine polycyclic ether poisonings, current therapy for ciguatera is primarily supportive. Gastric emptying, activated charcoal, and catharsis are recommended in the acute phase.5 Mannitol appears to reverse acute neurologic and gastrointestinal symptoms, although its use is mostly anecdotal.1,19 Palafox et al32 noted immediate reversal of 2 patients in a coma and 1 in shock with mannitol infusion. Improvement was noted by Pearn et al33 in 8 of 12 patients of variable severity after mannitol was given. Several anecdotal reports have suggested mannitol may work well after the acute phase of the illness.28,34 Mannitol is believed to reverse the effects of CTX by osmotically reducing sodium entry and causing an efflux of water from cells, and it may also act as a scavenger for hydroxyl radicals on the ciguatera molecule.13 During life-threatening reactions, dopamine and atropine will reverse hypotension and bradycardia, respectively. Acetaminophen, nonsteroidal anti-inflammatory drugs, and ascorbic acid relieve chronic neurological symptoms.1,23 Amitriptyline retrospectively diminished paresthesias when given to patients thought to have depression and is theorized to alter the response at the sodium channel.12,13 Pyridoxine, diazepam, nifedipine, Vitamin B, pralidoxime, protamide, fluoxetine, and corticosteroids have all been used with variable success.24 A
Farstad and Chow Table 2. Symptoms of ciguatera Gastrointestinal (common/early onset/lasts 1 to 2 days) Nausea Vomiting Diarrhea Abdominal pain Hypersalivation Cardiovascular (uncommon/early onset/persists up to 1 week) Hypotension Bradycardia Tachycardia Other (Variable occurrence and onset) Chills Perspiration Fever Loss of hair and nails Conjunctivitis Acne Skin rash Malaise Neurologic (common/late onset*/prolonged symptoms) Mental status Delirium Coma Confusion Depression Motor Ataxia Spasticity Respiratory arrest Opthalmoplegia Seizures Paresis Diminished reflexes Weakness Tonic contractions Sensory Paresthesias Pardoxical dysesthesias Asthenia Headache Myalgia Dental pain Photophobia Blindness Vertigo Arthralgias Metallic taste Blurred vision Pruritus Dyspareunia Painful ejaculation Dysuria *Neurologic symptoms can occur early in the disease course, but they classically follow gastrointestinal and cardiovascular symptoms.
Ciguatera poisoning recent report links improvement in several patients to gabapentin, a drug occasionally used to treat neuropathic pain.35 Lidocaine theoretically offers advantages in cardiovascular toxicity because it blocks nerve conduction by decreasing membrane permeability of sodium ions, and it may block the ciguatoxin-modified sodium channel.17,24 Alcohol and vigorous exercise seem to exacerbate neurotropic symptoms and should be avoided for at least several months.7,14 For unknown reasons, nonreef fish and shellfish products can precipitate the reappearance of neurotoxic symptoms.13 Ciguatera patients are described as being intolerant of cyclic ethers such as morphine sulfate, and paraldehyde.23 Many other substances have been hypothesized to cause the reemergence of symptoms; however, the occurrence of such is rare.13,23 Exposure to low levels of ciguatoxin may precipitate an exacerbation in some preexposed individuals; thus, reef fish with otherwise subthreshold toxin levels might cause symptoms in this group.12 Numerous practices have been used to determine if fish are toxic, none of which is adequately sensitive. Some cultures feed suspect fish to pets and observe them for ill effects. One man was said to repeatedly test suspect fish by feeding them to his mother-in-law.13 Animal and immunoassays have traditionally been considered nonspecific, although reverse-phase high-performance liquid chromatography/mass spectrometry is offering new promise.36 Related marine toxins TOXINS ASSOCIATED WITH CIGUATERA OUTBREAKS Ciguatoxins are considered the primary toxins in ciguatera poisoning, but maitotoxin, palytoxin, okadaic acid, and other marine toxins have been recovered from ciguatoxic fish. Most of these toxins belong to a group of compounds referred to as ‘‘polycyclic ethers.’’4 Maitotoxin is isolated from G toxicus cultures, but its role in ciguatera poisoning remains uncertain.14 Maitotoxin is a potent water-soluble toxin with hemolytic properties and profound hypotensive effects after in vitro injection; however, its low oral potency may limit its role in human poisonings.14,23 Maitotoxin is primarily concentrated in the fish’s liver and may play a role in severe reactions occurring when the organs of fish are consumed. Palytoxins are another potent group of polyether toxins that may play a part, or be confused with, ciguatera.14 In addition to crabs, fish, and marine worms, palytoxin has been isolated in ciguatoxic fish, as well as G toxicus and O lenticularis cultures.3 Ingestion of paly-
267 toxin results in severe headaches, paresthesias, skin irritation, paralysis, and intense tonic muscle contractions resulting in rhabdomyolysis.37 Palytoxin is reported to be a potent vasoconstrictor that can cause organ anoxia and ischemia.3 Ciguatera does not classically produce rhabdomyolysis or organ ischemia; thus, it is reasonable to consider a coexistent toxin such as palytoxin when these findings are combined with a usual ciguatera presentation. Finally, okadaic acid is one of a class of marine polyether toxins including dinophysistoxins and pectinotoxins causing secretory diarrhea in humans.3 Dinoflagellates containing okadaic acid have been linked to ciguatera outbreaks, and the presence of the toxin in ciguatoxic fish alludes to a possible connection to ciguatera poisoning.14 TOXINS NOT ASSOCIATED WITH CIGUATERA OUTBREAKS Like ciguatoxin, saxitoxin, tetrodotoxin, and brevetoxins are marine toxins specific to voltage-gated sodium channels; however, unlike okadaic acid and maitotoxin, an association with ciguatera outbreaks has not been described. We briefly mention these toxins to assist in developing a differential for these related marine poisonings. Saxitoxin is one of several dinoflagellate-associated toxins responsible for paralytic shellfish poisoning.3 Bivalve mollusks, fish, shrimp, and lobsters are known transvectors of saxitoxin poisoning, and although one mussel may contain as much as 50 mg, as little as 0.1 mg may be lethal.1 Paresthesias begin within 30 minutes of saxitoxin ingestion and progress to vomiting, muscle paralysis, and respiratory arrest within hours. Tetrodotoxin is a notorious marine poison and is found in many animals including puffer fish, crabs, ocean sunfish, starfish, blue ringed octopus, and Central American frogs.1,2 Fugu, a puffer fish, is still a cause of food poisoning deaths in Japan. Paresthesias and an unusual floating sensation progress quickly to ascending muscle paralysis, seizures, and respiratory arrest. Direct action on vascular smooth muscle and inhibition of vasomotor nerves precipitate hypotension, and some victims experience bradycardia.5 If saxitoxin or tetrodotoxin ingestion is suspected, gastric lavage with 2% sodium bicarbonate has been suggested, as polycyclic ethers lose their stability in basic solutions. Brevitoxins produced by the red tide dinoflagellate Ptychodiscus brevis are implicated in neurotropic shellfish poisoning, and, despite the name, fish also serve as hosts. Brevitoxin poisoning is associated with mild cardiovascular and respiratory depression, paresthesias, local cutaneous irritation, and other neurologic dysfunc-
268 tion.38 The toxins are selectively lethal to fish and are presumably unable to concentrate to levels sufficient to cause severe human poisoning.14 Ciguatera poisoning is more likely to be confused with brevitoxin exposure than the syndromes caused by saxitoxin or tetrodotoxin. Summary Outbreaks of ciguatera are unpredictable. In Venezuela, 200 cases on a cruise ship resulted in several fatalities.4 An outbreak of cases in Southern California was tracked to grouper harvested off the coast of the Baja peninsula during an El Nin˜o year.10 Patients with unexplained neurologic symptoms or with any acute gastrointestinal illness should be questioned about recent fish consumption. Supportive care is typically all that is needed; however, acute life-threatening reactions and chronic debilitating symptoms do occur. Mannitol appears to be an effective antidote, although it remains unclear why. Immunoassays are being refined to screen both fish and humans. In light of recent advances in marine toxicology, defining ciguatera in terms of a distinct clinical syndrome is unrealistic. The disease presents as a montage of symptoms caused by a variety of toxins and is probably confused with other similar intoxicants. Considering the worldwide prevalence of ciguatera, it is startling how many physicians are unfamiliar with this disease. The diagnosis is usually suggested by the history, yet patients seeking care far from endemic areas are often misdiagnosed. The popularity of tropical vacations and the increased availability of exotic frozen fish may well increase the incidence of ciguatera in North America.
Farstad and Chow
9.
10.
11.
12. 13. 14.
15.
16. 17.
18.
19. 20.
References 1. Eastough J, Sheperd S. Infections and toxic syndromes from fish and shellfish consumption. Arch Intern Med. 1989;149:1735–1739. 2. Brown CK, Shepherd SM. Marine trauma, envenomations, and intoxications. Emerg Med Clin North Am. 1992;10: 401–403. 3. Tosteson TR. The diversity and origins of toxins in ciguatera fish poisoning. PR Health Sci J. 1995;14:117–129. 4. Doorenbos N. Ciguatera toxins: where do we go from here? In: Seafood Toxins. Washington, DC: American Chemical Society; 1984:69–73. 5. Sakamoto Y, Lockey RF, Krzanowski JJ. Shellfish and fish poisoning related to the toxic dinoflagellates. South Med J. 1987;80:866–870. 6. Broadbent G. Ciguatera. Aust Fam Physician. 1987;16: 127–128. 7. Hampton MT, Hampton AA. Ciguatera fish poisoning. J Am Acad Dermatol. 1989;20:510–511. 8. Geller RJ, Olson KR, Senecal PE. Ciguatera fish poisoning
21.
22.
23.
24. 25.
26.
in San Francisco, California, caused by imported barracuda. West J Med. 1991;155:639–642. Bagnes R, Spiegel A, Nguyen L, Plichart R. Public health, epidemiological and socioeconomic patterns of ciguatera in Tahiti. Proceedings of the Third International Conference on Ciguatera Fish Poisoning. 1992; Puerto Rico. Quebec, Canada: Polyscience Publications; 1992. Barton ED, Tanner P, Turchen SG, Tunget CL, Manoguerra A. Ciguatera fish poisoning—a southern California epidemic. West J Med. 1995;163:31–35. Morris PD, Campbell DS, Freeman JI. Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters. South Med J. 1990;83:379–381. Lange WR. Ciguatera fish poisoning. Am Fam Physician. 1994;50:579–584. Swift AEB, Swift TR. Ciguatera. J Toxicol Clin Toxicol. 1993;31:777–781. Lewis RJ, Holmes MJ. Origin and transfer of toxins involved in ciguatera. Comp Biochem Physiol. 1993;106C: 615–628. Rougerie F, Bagnis R. Bursts of ciguatera and endo-upwelling process on coral reef. Bull Soc Pathol Exot. 1992; 85:464–466. Glaziou P, Legrand AM. The epidemiology of ciguatera fish poisoning. Toxicon. 1993;32:863–873. Lewis RJ, Hoy AW. Comparative action of three major ciguatoxins on guinea-pig atria and ilea. Toxicon. 1993; 31:434–446. Cameron J, Flowers AE, Capra MF. Modification of the peripheral nerve disturbance in ciguatera poisoning in rats with lidocaine. Muscle Nerve. 1993;16:782–786. Lewis RJ, Hoy AW, Mcgiffin DC. Action of ciguatoxin on human atrial trabeculae. Toxicon. 1992;30:907–914. Benoit E, Juzans P, Legrand AM, Molgo J. Nodal swelling produced by ciguatoxin-induced selective activation of sodium channels in myelinated nerve fibers. Neuroscience. 1996;71:1121–1131. Satake M, Ishibashi Y, Legrand AM, Yasumoto T. Isolation and structure of ciguatoxin-A4, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdicus toxicus and parrot fish Scarus gibus. Biosci Biotechnol Biochem. 1996;60:2103–2105. Katz AR, Terrell-Perica S, Sasaki DM. Ciguatera on Kauai: investigation of factors associated with severity of illness. Am J Trop Med Hyg. 1993;49:448–454. Sims JK. A theoretical discourse on the pharmacology of toxic marine ingestions. Ann Emerg Med. 1987;16:1006– 1013. Schatz IJ. Ciguatera fish poisoning: a jet age peril. Hosp Pract. 1989;24:79–94. Boisier P, Ranaivoson G, Rasolafonirana N, Andriahefazafy R, Roux J. Fatal mass poisoning in Madagascar following ingestion of a shark (Carcharhinus leucas): clinical and epidemiological aspects and isolation of toxins. Toxicon. 1994;33:1359–1364. Bagnis R, Kuberski T, Laugier S. Clinical observations on
Ciguatera poisoning
27.
28.
29. 30.
31. 32.
33.
3009 cases of ciguatera (fish poisoning) in the South Pacific. Am J Trop Med Hyg. 1979;28:1067–. Cameron J, Capra MF. The basis of the paradoxical disturbance of temperature perception in ciguatera poisoning. J Toxicol Clin Toxicol. 1993;31:571–579. Fenner PJ, Lewis RJ, Williamson JA, Williams ML. A Queensland family with ciguatera after eating coral trout. Med J Aust. 1997;166:473–475. Lipkin KM. Ciguatera poisoning presenting as a psychiatric disorder. Arch Gen Psychiatry. 1989;46:384–385. Lange WR, Lipkin KM, Yang GC. Can ciguatera be a sexually transmitted disease? J Toxicol Clin Toxicol. 1989; 27:193–197. Hughes JM, Meison MH. Fish and shellfish poisoning. N Engl J Med. 1976;295:1117–1120. Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA. 1988;259:2740–2742. Pearn JH, Lewis RJ, Ruff T, Tait M, Quinn J. Ciguatera
269
34.
35.
36.
37. 38.
and mannitol: experience with a new treatment regimen. Med J Aust. 1989;151:77–80. Blythe DG, De Sylva DP, Fleming LE, Ayyar RA, Baden DG. Clinical experience with IV mannitol in the treatment of ciguatera fish poisoning. Bull Soc Pathol Exot. 1993; 85:425–426. Perez C, Vasquez PA, Penet CF. Treatment of ciguatera poisoning with gabapentin. [Letter]. N Engl J Med. 2001; 344:692–693. Lewis RJ, Jones A, Vernoux JP. HPLC/tandem electrospray mass spectrometry for the determination of sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish. Anal Chem. 1999;71:247–250. Lange WR. Puffer fish poisoning [Review]. Am Fam Physician. 1990;42:1029–1033. Bagnis R, Chanteau S, Chungue E. Origins of ciguatera fish poisoning—a new dinoflagellate, Gambierdicus toxicus Adachi and Fulcuyo, definitively involved as a causal agent. Toxicon. 1980;18:199–208.