Transcript Ciguatera - UNC School of Medicine

ID Case Conference
January 9, 2008
Carlos M. Perez, MD, FACP
Associate Professor of Medicine
Pontificia Universidad Catolica de Chile
Case 1 & 2
• HPI: Two women (sisters in law), 30 yo
and 37 yo respectively, while they were on
vacations with their husbands and children
(three each), in Punta Cana, Dominican
Republic, developed similar symptoms.
They saw several Physicians before
coming to see us.
Case 1 & 2
• HPI Patient # 1: Episode of watery diarrhea. Several
hours later, dysesthesia developed, along with
intense pruritus of the legs, hands, and breasts,
which increased with exposure to cold.
• HPI Patient # 2: Episode of watery diarrhea. Several
hours later developed dysesthesia, generalized
pruritus and sharp, shooting pain in her legs.
• In both patients, the symptoms were disabling and
persisted for weeks. They are sportswomen and
denied eating “junk food” as their families did. No
mosquito bites. No consumption of uncooked
shellfish/fish. No contact with animals. Husbands
and children were healthy and asymptomatic.
Case 1 & 2
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PMH & PSH: Unremarkable
Medications: Acetaminophen, Ibuprofen.
NKDA
SH: Married, three children. No sexual
contact other than husband. No Etoh or
tobacco use.
• ROS: Fever(-), weight loss (-), skin rash (-),
HA (-), insomnia (+) (due to pruritus and
pain), GI symptoms (-) except for initial
diarrhea. Join pain or swelling (-)
Case 1 & 2
• PE: Both afebrile, normal pulse and
BP. No skin rash. No
lymphadenopathy. HEENT wnl. Lungs
and Heart wnl. Breasts wnl. Abdomen
wnl.
• Neurological examination: Mental
status wnl. Normal sensation and
strength. Normal reflexes. Meningeal
signs (-)
Case 1 & 2
• Laboratory test: CBC, chemistry, UA,
Sed rate, CRP wnl.
Case 1 & 2
Discussion
Case 1 & 2
Diagnosis:
Ciguatera Poisoning
Case 1 & 2
Diagnosis:
Ciguatera Poisoning
How they got it?
Case 1 & 2
Because they ate Dusky grouper (“Mero”)
(Epinephelus marginatus)
Marine Toxins
• As world travel and trade grow, physicians are
increasingly likely to encounter patients suffering
from marine toxins. The world's oceans harbor
hundreds of different types of marine toxins, and
the epidemiology and clinical manifestations of
these toxins vary widely.
• The most frequent are: ciguatera, scombroid,
paralytic shellfish poisoning, neurotoxic shellfish
poisoning, diarrheic shellfish poisoning, and
pufferfish poisoning
• See Table #1 from Marine Toxins in UpToDate
(on campus access only)
Ciguatera
• Named by the Portuguese biologist Parra in
1771, ciguatera toxicity has existed in the tropics
for centuries. Some authors have speculated
that Alexander the Great refused to let his troops
eat fish because of ciguatera.
• Ciguatera poisoning accounts for more than half
of the fish-related foodborne disease outbreaks
in the United States, and is the most common
fish food poisoning in tropical coastal regions.
An estimated 20,000 to 50,000 people develop
ciguatera each year throughout the world.
Ciguatera
• Most cases originate in the tropics and
subtropics, between 35 degrees north
latitude and 35 degrees south latitude.
• Two cases of ciguatera poisoning reported
in 2004 represent the first known cases
caused by fish (barracuda) caught off the
coast of South Carolina.
Ciguatera
• More than 400 different fish species have
been associated with ciguatera. Reefdwelling tropical fish such as barracuda,
moray eel, amberjack, and certain types of
grouper, mackerel, parrotfish, and red
snapper are the most common sources of
ciguatera toxicity.
Ciguatera
• Pathogenesis: Ciguatera is caused by
several distinct toxins, of which ciguatoxin is
the best known. These toxins are formed by
dinoflagellates of the genus Gambierdiscus,
single-celled algae-like organisms that grow
on and around coral reefs. Gambierdiscus
toxicus, which produces ciguatoxin, tends to
proliferate on denuded coral surfaces.
Ciguatera
• Pathogenesis: The toxin is transferred
through hervivorous reef fish to
carnivorous reef fish which are consumed
by humans. Ciguatera toxin-containing fish
does not taste, smell, or appear unusual.
Cooking, marinating, freezing, and stewing
fish does not destroy the toxins.
Ciguatera
• Pahogenesis: Ciguatoxin is a lipid soluble, heat
stable, acid resistant neurotoxin. It opens voltage
dependent sodium channels in cell membranes,
triggering membrane depolarization. Maitotoxin,
another ciguatera associated toxin, increases
calcium ion influx through excitable membranes.
Scaritoxin increases the permeability of sodium
channels and causes norepinephrine and
acetylcholine release.
Ciguatera
• Clinical manifestations: gastrointestinal
symptoms, including vomiting, diarrhea, and
abdominal cramping, beginning three to six
hours after eating contaminated fish, but the
incubation period may be up to 30 hours.
Neurologic symptoms usually begin 3 to 72
hours after the meal. The neurologic symptoms
can include paresthesias, painful teeth, painful
urination, blurred vision, nerve palsies, and
hot/cold temperature reversal. Cardiovascular
symptoms include bradycardia, heart block, and
hypotension.
Ciguatera
• Diagnosis: Clinical
• Fish can be tested using a mouse
bioassay and an IgG immunoassay, but
these tests are costly and time consuming
and are not widely used.
• In many tropical cultures, local inhabitants
believe that contaminated fish will not fight
back as hard as other fish, and that cats
will refuse contaminated fish.
Ciguatera
Treatment
Ciguatera
• One month after the onset of symptoms the
patients were treated with Gabapentin (400 mg
TID), with rapid improvement. Twenty days later,
we stopped the drugs; the symptoms returned in
a few hours in both patients. Gabapentin therapy
was resumed, and the patient had immediate
relief of symptoms.
• See Perez CM, Vasquez PA, Perret CF.
(2001)Treatment of ciguatera poisoning with
gabapentin.N Engl J Med,344(9):692-3.)
Ciguatera
Other Drugs used to treat Ciguatera Poisoning
Initial treatment of ciguatera is supportive. Multiple uncontrolled trials
have found that intravenous mannitol, given at a dose of 1 g/kg,
reduces neurologic symptoms when given within the first 48 hours.
See Abstract for Palafox, NA, Jain, LG, Pinano, AZ, et al. Successful
treatment of ciguatera fish poisoning with intravenous
mannitol. JAMA 1988; 259;2740
Amitriptyline and fluoxetine have been reported to benefit ciguatera
patients suffering from chronic fatigue, insomnia, and depression.
Gabapentin was reported to improve polyneuropathic symptoms in
two patients, but it is an expensive therapy.
See Blythe, DG, Hack E, Washington, G. The medical management of
seafood poisoning. Foodborne Disease Handbook: Seafood and
Environmental Toxins (vol. 4)
Search PubMed
• Ciguatera Poisoning
-Case Reports
-Reviews
-Differential Diagnosis
-Therapy