Rhabdomyolysis After Cooked Seafood Consumption (Haff Disease) in the United States vs China

INTRODUCTION

Although the health benefits from polyunsaturated fatty acid–rich seafood include protection from myocardial infarction and stroke, fish and shellfish can bioconcentrate algal toxins and cause cluster outbreaks of seafood poisoning. Haff disease is a syndrome characterized by myalgia often accompanied by myoglobinuria after the ingestion of cooked fish and crustaceans.^1-7 Haff disease targets and damages striated muscle and causes rhabdomyolysis with the release of myoglobin, creatine kinase (CK), and other muscle cell enzymes. The proposed mechanisms for acute renal failure in patients with rhabdomyolysis include the following: (1) blockage of the renal tubules with precipitated myoglobin, (2) cortical damage from oxygen free radicals, and (3) myoglobin-induced vasoconstriction of renal arterioles. The differential diagnosis of Haff disease includes other causes of seafood poisoning by heat-stable toxins—typically bioaccumulated red algal and blue-green algal toxins.^8,9

Haff disease is named for the Königsberg Haff, or lagoon, that borders the Baltic coasts of Russia and Poland, the site of the first reports of the disease in 1924.⁹ The US Centers for Disease Control and Prevention (CDC) defines Haff disease (also known as Haff-Iuksov-Sartlan disease and Iuksovsk-Sartlansk disease in Eastern Europe) as a painful myotoxic condition that meets the following criteria: (1) a positive cooked seafood ingestion history within 24 hours, (2) a markedly elevated (specifically a 5-fold or greater rise over normal) serum CK level, and (3) a CK-muscle/brain (MB) fraction <5%.^8,9

The objectives of this retrospective case series analysis were (1) to identify the most common seafood vectors of Haff disease in the United States and China; (2) to describe and to compare the most commonly recurring clinical and laboratory manifestations of Haff disease following crayfish and fish consumption in the United States and China—the two nations reporting the greatest number of Haff disease cases meeting the current CDC disease definition; and (3) to compare the Haff disease toxidrome with similar seafood poisoning toxidromes to further define the pathophysiologic mechanisms of poisoning and to expose potential causative aquatic toxins.

RESULTS

DISCUSSION

The results of this descriptive analytical comparison demonstrate that all confirmed Haff disease cases in the United States and China were characterized by muscle pain and laboratory evidence of rhabdomyolysis, but the seafood vectors, with the exception of boiled crayfish, differed. Although the comparative analysis of cases of rhabdomyolysis after crayfish consumption in the United States and China was limited by its small study sample size (n=15), it was epidemiologically significant for the following reasons: (1) the same species of boiled crayfish (P. clarkii) is a popular seasonal dish in Louisiana and in China, and (2) Chinese crayfish are popular imports in the United States.

Samples of the suspected seafood in 21 of the US cases reviewed in this article were tested by the CDC or the US Food and Drug Administration and were negative for the following aquatic toxins: ciguatoxin, saxitoxin, brevetoxin, tetrodotoxin, palytoxin, domoic acid, okadaic acid, and two blue-green algal or cyanobacterial toxins, microcystin, and nodularin.⁹ Subsequent government laboratory testing of toxic crayfish samples in China were also negative for marine toxins.^17-18 Although governmental and regional health laboratories in the United States and China have not identified the heat-stable myotoxin that causes Haff disease, mice that were fed samples of toxic buffalo fish developed histopathologic evidence of rhabdomyolysis with renal tubular myoglobin and myoglobinuria.^3,9

In 2001, 9 cases of Haff disease were reported by the Louisiana Office of Public Health in patients who resided within a 30-mile radius of each other in south-central Louisiana.¹¹ All patients were hospitalized for suspected myocardial infarction with the onset of chest pain, dyspnea, diaphoresis, and nausea 3-16 hours (mean, 8 hours) after consuming boiled crayfish purchased from the same seafood vendor.¹¹ Although the differential diagnosis of Haff disease includes myocardial infarction and other causes of toxic rhabdomyolysis, no specific laboratory tests exist for Haff disease other than the biomarkers of rhabdomyolysis.

In 2013, Xie et al reported a case of Haff disease in a 26-year-old male who had consumed boiled crayfish within 24 hours and presented with severe myalgias that lasted for nearly 3 months.¹⁸ His serum CK and lactic dehydrogenase were significantly elevated, and a biopsy of the left biceps brachii muscle demonstrated rhabdomyolysis histopathologically. A radioisotope (Tc-99)-labeled bone scan demonstrated increased radioisotope tracer uptake in nearly all muscle groups, especially in the proximal extremity musculature. The authors concluded that a presumptive diagnosis of Haff disease based on presenting clinical and laboratory features could be further supported by muscle biopsy and bone scan by precisely locating sites of rhabdomyolysis.

No antitoxin exists for Haff disease poisoning, and treatment is entirely supportive. The initial clinical presentation may mimic myocardial infarction that must be excluded by normal electrocardiograms, serum troponin (troponin I and T) levels, and serum CK-MB levels <5%. Intravenous fluid hydration is required to maintain urine output and prevent the intratubular accumulation of myoglobin. In addition to intravenous fluid therapy, the management of rhabdomyolysis includes correction of metabolic acidosis, intravenous infusion of sodium bicarbonate to promote urinary alkalinization, and the use of intravenous mannitol as an antioxidant and osmotic diuretic to further minimize the nephrotoxic effects of intratubular myoglobin.²³ If these supportive therapies fail, extracorporeal renal replacement techniques, including hemofiltration and hemodialysis, may be instituted.²³ Severe myalgias may require management with intravenous opioids for pain control, and muscular spasm and rigidity may require management with benzodiazepines. Following successful management, most patients will have complete recovery without residual effects.

CONCLUSION

Haff disease in the United States most commonly may follow the ingestion of buffalo fish, but it may also follow the ingestion of crayfish and Atlantic salmon. Clusters of Haff disease have followed the consumption of boiled crayfish of the same species in the United States and China. The early identification of the seafood vectors of Haff disease will control outbreaks and prevent additional cases when seasonal conditions cause seafood to become myotoxic. The bioaccumulation of a new, heat-stable freshwater and/or brackish/saltwater algal toxin in seafood, similar to palytoxin but primarily myotoxic and not neurotoxic, is suspected of causing Haff disease. Haff disease most closely resembles marine palytoxin poisoning without significant neurotoxicity. More toxicologic investigations in larger case clusters are recommended to identify the toxin responsible for Haff disease.