PAR2, Keratinocytes, and Cathepsin S Mediate the Sensory Effects of Ciguatoxins Responsible for Ciguatera Poisoning.

Ciguatera fish poisoning is caused by the consumption of fish contaminated with ciguatoxins (CTXs). The most distressing symptoms are cutaneous sensory disturbances, including cold dysesthesia and itch. CTXs are neurotoxins known to activate voltage-gated sodium channels, but no specific treatment exists. Peptidergic neurons have been critically involved in ciguatera fish poisoning sensory disturbances. Protease-activated receptor-2 (PAR2) is an itch- and pain-related G protein‒coupled receptor whose activation leads to a calcium-dependent neuropeptide release. In this study, we studied the role of voltage-gated sodium channels, PAR2, and the PAR2 agonist cathepsin S in the cytosolic calcium increase and subsequent release of the neuropeptide substance P elicited by Pacific CTX-2 (P-CTX-2) in rat sensory neurons and human epidermal keratinocytes. In sensory neurons, the P-CTX-2‒evoked calcium response was driven by voltage-gated sodium channels and PAR2-dependent mechanisms. In keratinocytes, P-CTX-2 also induced voltage-gated sodium channels and PAR2-dependent marked calcium response. In the cocultured cells, P-CTX-2 significantly increased cathepsin S activity, and cathepsin S and PAR2 antagonists almost abolished P-CTX-2‒elicited substance P release. Keratinocytes synergistically favored the induced substance P release. Our results demonstrate that the sensory effects of CTXs involve the cathepsin S-PAR2 pathway and are potentiated by their direct action on nonexcitable keratinocytes through the same pathway.

Junctional bradycardia caused by ciguatera intoxication.

Ciguatera is a common but underreported tropical disease caused by the consumption of coral reef fish contaminated by ciguatoxins. Gastrointestinal and neurological symptoms predominate, but may be accompanied by cardiovascular features such as hypotension and sinus bradycardia. Here, we report an unusual case of junctional bradycardia caused by ciguatera in the Caribbean; to our knowledge, the first such report from the region. An increase in global sea temperatures is predicted to lead to the spread of ciguatera beyond traditional endemic areas, and the globalisation of trade in coral reef fish has resulted in sporadic cases occurring in developed countries far away from endemic areas. This case serves as a reminder to consider environmental intoxications such as ciguatera within the differential diagnosis of bradycardias.

[Ciguatera or why you should enquire about fish consumption in cases of cold allodynia]. / Ciguatera oder wieso bei der Kälteallodynie nach dem Fischverzehr gefragt werden sollte.

Ciguatoxine sind potente, von Mikroalgen produzierte, marine Biotoxine, die sich in tropischen Raubfischen, lokal und saisonal unterschiedlich stark, anreichern können. Kurze Zeit nach dem Fischverzehr treten gastrointestinale, neurologische und/oder kardiovaskuläre Vergiftungssymptome auf. Durch die hohe Affinität der Toxine zu neuronalen Natriumkanälen sind neurologische Symptome für Ciguatera-Vergiftungen charakteristisch. Nahezu pathognomonisch ist dabei die Kälteallodynie, bei der kalte Oberflächen als heiß, schmerzhaft oder extrem unangenehm empfunden werden. Durch Importe von Tropenfisch tritt Ciguatera zunehmend auch in gemäßigten Klimazonen auf. Wir erläutern anhand zweier Fälle die Besonderheiten dieser Fischvergiftung.

Intractable Seizures and Rehabilitation in Ciguatera Poisoning.

Ciguatera fish poisoning is the most frequently reported seafood toxin illness associated with the ingestion of contaminated tropical fish. Diagnosis relies on a history of recent tropical fish ingestion and subsequent development of gastrointestinal, cardiovascular, and neurological symptoms. Ciguatera poisoning usually has a self-limited time course, and its management involves symptomatic control and supportive care. This case report presents an uncommon case of ciguatera poisoning with prolonged intractable seizures refractory to standard antiseizure medications. The patient also had significant functional decline that responded to rigorous inpatient rehabilitation not previously described in literature.

Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin.

BACKGROUND: Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light. There are few treatment options for ciguatera CIRS since little is known about its pathophysiology. METHODS: This study characterizes the transcriptional profile in whole blood of 11 patients with ciguatera-induced CIRS and 11 normal controls run in duplicate using Agilent one color whole genome microarrays. Differential expression was determined by using a combination of moderated t-test p-value and fold change (FC). Significant genes were subjected to gene ontology, principal component analysis and SVM classification. Seven significant genes found by microarray were validated by PCR. RESULTS: Using a low stringency (p < 0.05 and FC > 1.4) and a high stringency (p < 0.01 and FC > 1.5) filter, the resulting gene sets of 185 and 55, respectively, showed clear separation of cases and controls by PCA as well as 100% classification accuracy by SVM, indicating that the gene profiles can separate patients from controls. PCR results of 7 genes showed a 95% correlation to microarray data. Several genes identified by microarray are important in wound healing (CD9, CD36, vWF and Factor XIII), adaptive immunity (HLA-DQB1, DQB2, IL18R1 and IL5RA) and innate immunity (GZMK, TOLLIP, SIGIRR and VIPR2), overlapping several areas shown to be disrupted in a mouse model of acute exposure to ciguatoxin. Another area of interest was differential expression of long, non-coding sequences, or lncRNA. CONCLUSIONS: Disruptions of innate and adaptive immune mechanisms were recorded at both the genomic and proteomic level. A disruption in the HLA-T cell receptor axis could indicate HLA haplotype sensitivity for this chronic syndrome, as noted in many autoimmune conditions. Taken together, these indicators of illness provide additional insights into pathophysiology and potential therapies.

Caso de intoxicación por ciguatera en paciente pediátrico / A case of ciguatera poisoning in a paediatric patient

No disponible

[Ciguatera fish poisoning]. / La ciguatéra.

Ciguatera, an ichtyosarcotoxism linked to the consumption of usually healthy coral fish is a common poisoning in the Pacific, Caribbean and Indian Ocean where it is endemic. However, increased tourism and commercial transportation of tropical fish for consumption make it an unexceptional intoxication in countries away from its endemic area. Environmental stresses such as climate changes also contribute to the expansion of its geographical area. The non-specific clinical symptomatology is characterized by the occurrence of gastrointestinal, cardiovascular, nervous and general signs few hours after eating a ciguatoxic fish. The diagnosis is clinical and relatively easy in endemic areas but much less for physicians who are rarely confronted with, which is a source of prolonged diagnostic delays and a significant increase in spending. Treatment of ciguatera is symptomatic but new treatments, still experimental, give a real hope for the future.

Ciguatera poisoning in the Cook Islands.

This case report presents two British medical students who contracted ciguatera poisoning while on elective in the Cook Islands. Thirty-six hours after consuming two reef fish they developed paraesthesia of the mouth, hands and feet, myalgia, pruritis and cold allodynia. Neurological examination was normal. Diagnosis of ciguatera poisoning was made on history of reef fish consumption and classical clinical presentation. Management was symptomatic (antihistamines) and both students made a full recovery within 10 weeks.

Severe bradycardia and prolonged hypotension in ciguatera.

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

Reversible cerebellar dysfunction associated with ciguatera fish poisoning.

BACKGROUND: Ciguatera-fish poisoning (or ciguatera) is a common but underdiagnosed food-borne illness related to fish consumption that is characterized by nausea, vomiting and neurologic symptoms such as tingling in the fingers or toes. OBJECTIVE: We describe the case of a young man who suffered from diarrhea and abdominal pain after eating raw fish and who also developed severe ataxia with spontaneous downbeat and perverted head-shaking nystagmus. CASE REPORT: The patient experienced visual fixation suppression failure during the bithermal caloric test and bilateral smooth-pursuit impairment. Oculomotor findings suggested dysfunction of the vestibulocerebellum, especially the flocculus. CONCLUSION: These findings suggest that both the peripheral and the central nervous systems can be involved in ciguatera.

[Ciguatera and acute polyradiculoneuritis. Description of two cases in French Polynesia: immunoallergic hypothesis?]. / Ciguatéra et polyradiculonévrite aiguë a propos de deux cas en Polynésie française: hypothèse immuno-allergique?

Ciguatera is a foodborne poisoning caused by eating seafood from tropical and subtropical reef areas. According to official data from the local health department, cases of ciguatera in French Polynesia are estimated to involve 240 to 400 persons per 100 000 inhabitants. Associated with a wide spectrum of gastrointestinal, cardiovascular, nervous, and general signs, ciguatera is usually benign although some forms can lead to hospitalization. The purpose of this report is to describe two unusual cases involving patients who developed acute polyradiculoneuritis with Guillain-Barré-syndrome-like peripheral nervous system deficits on the seventh day of ciguatera after ingestion of moray eel. The hypothesis of an immune-allergic reaction is raised especially in the light of rapid improvement of the patient who received polyvalent immunoglobulin treatment.

Cluster of ciguatera fish poisoning--North Carolina, 2007.

Ciguatera fish poisoning (CFP) is a distinctive type of foodborne disease that results from eating predatory ocean fish contaminated with ciguatoxins. As many as 50,000 cases are reported worldwide annually, and the condition is endemic in tropical and subtropical regions of the Pacific basin, Indian Ocean, and Caribbean. In the United States, 5--70 cases per 10,000 persons are estimated to occur yearly in ciguatera-endemic states and territories. CFP can cause gastrointestinal symptoms (nausea, vomiting, abdominal cramps, or diarrhea) within a few hours of eating contaminated fish. Neurologic symptoms, with or without gastrointestinal disturbance, can include fatigue, muscle pain, itching, tingling, and (most characteristically) reversal of hot and cold sensation. This report describes a cluster of nine cases of CFP that occurred in North Carolina in June 2007. Among the nine patients, six experienced reversal of hot and cold sensations, five had neurologic symptoms only, and overall symptoms persisted for more than 6 months in three patients. Among seven patients who were sexually active, six patients also complained of painful intercourse. This report highlights the potential risks of eating contaminated ocean fish. Local and state health departments can train emergency and urgent care physicians in the recognition of CFP and make them aware that symptoms can persist for months to years.

Ciguatera fish poisoning with elevated muscle enzymes and abnormal spinal MRI.

We report three cases of ciguatera fish poisoning. One patient died secondary to respiratory failure. Two patients showed elevated muscle enzymes and one patients had an abnormal cervical spinal MRI. MRI findings have not been previously described. MRI findings explain the mechanism of the L'hermitte phenomenon (a common complaint) among these patients. Respiratory failure is rare in ciguatera fish poisoning. Our findings suggest this could be related to respiratory muscles involvement.