Chronic Ciguatera Poisoning: A Case Report

Abstract

Ciguatera is a common marine, toxin-borne illness caused by the consumption of fish that contain toxins that activate voltage-sensitive sodium channels. The clinical manifestations of ciguatera are typically self-limited, but chronic symptoms may occur in a minority of patients. This report describes a case of ciguatera poisoning with chronic symptoms, including pruritus and paresthesias. A 40-y-old man was diagnosed with ciguatera poisoning after consuming amberjack while vacationing in the US Virgin Islands. His initial symptoms, including diarrhea, cold allodynia, and extremity paresthesias, evolved into chronic, fluctuating paresthesias and pruritus that became worse after the consumption of alcohol, fish, nuts, and chocolate. After a comprehensive neurologic evaluation failed to reveal another cause for his symptoms, he was diagnosed with chronic ciguatera poisoning. His neuropathic symptoms were treated with duloxetine and pregabalin, and he was counseled to avoid foods that triggered his symptoms. Chronic ciguatera is a clinical diagnosis. Signs and symptoms of chronic ciguatera can include fatigue, myalgias, headache, and pruritus. The pathophysiology of chronic ciguatera is incompletely understood but may involve genetic factors or immune dysregulation. Treatment involves supportive care and avoidance of foods and environmental conditions that may exacerbate symptoms.

Introduction

Ciguatera fish poisoning is a common marine, toxin-borne illness characterized by gastrointestinal, neurologic, and cardiac signs and symptoms. Although most patients affected by ciguatera experience a self-limited syndrome, some individuals may experience recurrent or chronic symptoms. The chronic manifestations of ciguatera poisoning are infrequently encountered in clinical practice but can be physically and mentally debilitating for affected patients. This report describes a case of chronic ciguatera poisoning that occurred after the consumption of amberjack fish at a tropical destination. Written consent for publication of the case report was obtained from the patient described in this report.

Case Report

While on vacation in the US Virgin Islands, a 40-y-old man with a history of gout and anxiety consumed a 170-g filet of grilled amberjack that he had caught during a reef fishing excursion. His wife and friends, who were on the excursion with him, ate smaller portions of the fish. Six hours later, he developed nausea, watery diarrhea, and perioral paresthesias. The paresthesias evolved into cold allodynia and a tingling sensation involving his hands and feet. He was evaluated at a local clinic, where he was diagnosed with ciguatera and treated with IV hydration. His wife and friends also experienced similar symptoms that were less severe in intensity.

After he returned home from vacation, he experienced persistent cold allodynia and paresthesias of his hands and feet. Cold liquids tasted sour and carbonated to him, and he felt lower-extremity myalgias and itching as well as headaches. The patient’s wife and friends did not experience similar symptoms. The results of laboratory testing, including complete blood count and electrolyte and hemoglobin A1c measurements, were unremarkable. The patient was referred for neurology and medical toxicology evaluations. Magnetic resonance imaging of the spine yielded unremarkable results, and electromyography (EMG) findings were suggestive of mild, generalized sensory-motor peripheral neuropathy. Duloxetine and pregabalin were prescribed for his neuropathic symptoms. Six weeks after the initial onset of symptoms, the patient reported having worsening paresthesias after he consumed peanuts. These persistent symptoms, including paresthesias and pruritus, fluctuated in intensity over the next year and were typically more severe when he ingested beer, chocolate, nuts, or fish. The patient was advised to avoid the consumption of foods that triggered his symptoms until complete resolution of the paresthesias and pruritus occurred.

Discussion

Ciguatera, the most common marine poisoning worldwide, is caused by the consumption of fish contaminated with ciguatoxins and gambiertoxins, which activate voltage-sensitive sodium channels. ¹ Coral reefs harbor microalgae, including Gambierdiscus, that produce namesake toxins, which then bioaccumulate up the food chain. ² Human consumption of contaminated tropical reef fish, including amberjack, barracuda, and moray eel, results in the clinical signs and symptoms of ciguatera. Because ciguatoxins are heat stable and lack a distinct odor or taste, they are not inactivated by cooking methods and are associated with minimal warning properties prior to the onset of symptoms. The severity of illness is often proportional to the amount of fish consumed, and more severe signs and symptoms have been reported to occur after the ingestion of certain fish parts, including the head, liver, and gonads. ³ This is consistent with the case described here, where the most severe and persistent symptoms occurred in the patient who consumed the largest amount of fish.

Clinical manifestations of ciguatera include gastrointestinal, neurologic, and cardiac signs and symptoms that typically begin within 6 h after the consumption of contaminated fish. ⁴ Nausea, vomiting, and diarrhea are often followed by perioral and extremity paresthesias, itching, and cold allodynia. ² Bradycardia, atrioventricular conduction delays, and hypotension are uncommon manifestations of ciguatera. ⁵ The signs and symptoms of ciguatera typically resolve over a period of several days. ⁴

Although ciguatera is typically a self-limiting illness, recurrent or persistent symptoms can also occur. Chronic manifestations of ciguatera affect up to 20% of affected individuals and may persist for months to years after initial diagnosis.^3,6 Signs and symptoms of chronic ciguatera include fatigue, myalgia, arthralgia, headache, and pruritus. ¹ Patients affected by chronic ciguatera may also exhibit neurocognitive dysfunction; in 1 study, rats exposed to recurrent oral doses of ciguatoxin were found to have anxiety-like behavior, learning deficits, and memory impairments. ⁷ The signs and symptoms of chronic ciguatera can fluctuate in intensity and may be exacerbated by consumption of alcohol, nuts, meat, and nonciguatoxic fish, as well as by exposure to ambient temperature changes, sunlight, and physical activity. ⁶ In 1 study, increased age, tobacco use, acute bradycardia, and elevated blood concentrations of urea and neutrophils were found to be potential predictive factors for the development of chronic ciguatera, although other investigations did not identify these risk factors.^3,6 In another prospective study, patients with more extensive initial symptoms of ciguatera were also more likely to develop chronic disease. ³ The pathophysiology of chronic ciguatera is poorly understood but may involve genetic abnormalities or immune dysregulation. ⁸ Lopez et al ⁹ detected significant differences in gene expression in peripheral blood lymphocytes of patients with chronic ciguatera compared with that in those of individuals who experienced self-limited ciguatera, suggesting that the development of chronic or recurrent symptoms is related to genetic factors.

The diagnosis of chronic ciguatera is clinical; laboratory assays for the detection of ciguatera are not readily available in most clinical settings and are of limited utility in patients who present with persistent symptoms distant from the time of exposure. In the case presented here, the patient’s signs and symptoms, in addition to his history of consumption of reef fish, supported the diagnosis of ciguatera. Subsequent neurologic evaluation, including laboratory testing and results of the imaging studies and EMG, did not reveal a more likely diagnosis for this patient’s chronic symptoms.

There is no standard therapy for chronic ciguatera poisoning, and supportive symptomatic care is the primary treatment option. Historically, the administration of IV mannitol has been recommended as a treatment option for acute ciguatera poisoning, although limited data support its effectiveness. ¹⁰ There is minimal evidence suggesting that mannitol is effective for the treatment of chronic ciguatera. ¹¹ One case report has suggested that fluoxetine attenuates chronic fatigue associated with chronic ciguatera, whereas other studies have recommend the use of amitriptyline or gabapentin for the treatment of persistent symptoms.^1,12 Diphenhydramine and cholestyramine, which have been mentioned in isolated reports as potential treatment options for ciguatera, have not been studied for the treatment of chronic symptoms. ¹¹ Given that patients affected by chronic ciguatera poisoning may experience both physical and neuropsychological impairments, neurocognitive testing and rehabilitation may be warranted for certain individuals. As noted in the case described here, avoidance of potentially triggering foods or environments can also prevent exacerbation of symptoms. Unfortunately, the prolonged nature of chronic ciguatera may be distressing and potentially disabling for many patients. In some cases, the chronic sequelae of ciguatera can persist for years. ¹²

The patient described in this case had a history of anxiety, which may have complicated the evaluation and diagnosis of his chronic symptoms. Chronic ciguatera poisoning is associated with depression and anxiety, and some clinical manifestations of these conditions are similar to those of chronic ciguatera. ¹ Nonpharmacologic methods of treatment, including anticipatory education, continued reassurance, and cognitive behavioral therapy, may be beneficial in the treatment of anxiety related to or caused by chronic ciguatera. ¹³ Ciguatoxin exposure causes damage to neurons and astrocytes in the anterior aspect of the cingulate cortex, an area of the brain that modulates emotion and cognition and may have a causal role in anxiety disorders. ⁷ However, the exact relationship between chronic ciguatera and anxiety in humans remains unclear, and it is not known whether individuals with a history of anxiety disorder are more likely to develop chronic symptoms after ciguatera poisoning. In the case described here, it is difficult to determine whether the patient’s chronic ciguatera symptoms were exacerbated or otherwise affected by his underlying anxiety disorder.

Conclusion

Chronic manifestations, including fatigue, myalgias, and pruritus, may occur in up to 20% of patients affected by ciguatera. These signs and symptoms, which often fluctuate in intensity, can persist for months to years in some individuals. Supportive care, including neuropsychological evaluation and treatment as well as avoidance of triggering foods and environments, may improve clinical outcomes in individuals with chronic ciguatera.