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Haff Disease Associated with Eating Buffalo Fish -- United States, 1997
Haff disease is a syndrome of unexplained rhabdomyolysis following consumption of certain types of fish; it is caused by an unidentified toxin. Rhabdomyolysis is a clinical syndrome caused by injury to skeletal muscle that results in release of muscle cell contents into the circulation (1). In 1997, six cases of Haff disease were identified in the United States (four in California and two in Missouri) among persons who ate buffalo fish (Ictiobus cyprinellus), a bottom-feeding species found mostly in the Mississippi River or its tributaries. This report summarizes the investigation of these cases.
Los Angeles County, California
Patients 1 and 2. On March 8, two Ukrainian sisters (patients 1 and 2), aged 70 and 73 years, respectively, and the husband of patient 2 (aged 75 years) ate fried buffalo fish. Eight hours after the meal, patient 1 experienced neck pain followed by stiffness in her arms. On arrival, emergency medical technicians noted both women were rigid, unable to move, and extremely sensitive even to light touch. On evaluation at a local hospital, the serum creatine kinase (CK) of patients 1 and 2 were 25,000 IU/L and 9454 IU/L, respectively (normal: less than 120 IU/L); the muscle/brain (MB)-fraction at the peak of the CK was 2.7% and 0.5% (normal: less than 5%). Patient 1 was treated with intravenous hydration and bicarbonate. Patient 2, who had a history of angina pectoris, also complained of chest pain. During hospitalization, an angiogram revealed occlusion of a coronary artery requiring dilatation. She was treated with nitrates and coumadin. The man did not become ill. Both sisters recovered. Main sequelae were newly diagnosed hypertension (patient 1) and diminished muscular strength (patient 2).
Patient 3. On March 9, a husband and wife (both aged 33 years) from Ukraine ate fried buffalo fish purchased from the same market where patients 1 and 2 purchased their fish. Eight hours after the meal, the husband experienced left-sided chest pain that radiated to his left arm and increased with deep inspiration. He was admitted to the same hospital as patients 1 and 2. A comprehensive cardiovascular examination did not reveal abnormalities except an elevated CK (4140 IU/L) with a CK-MB of 1.4% at the peak of the CK. He reported no history of angina pectoris and had not smoked for 2 years. He did not receive any special treatment. Following discharge, the patient has reported occasional chest pain that he had not noticed before this episode. His wife did not become ill.
St. Louis, Missouri
Patients 4 and 5. On June 8, a Ukrainian husband and wife (aged 66 and 58 years, respectively) ate a dish consisting of ground buffalo fish and carp. One hour later, the wife vomited. Six hours after the meal, they developed generalized body aches and muscle stiffness. On evaluation at a local hospital, the CK of patients 4 and 5 exceeded 17,700 IU/L, and the CK-MB were 4.8% and 4.5%, respectively. The husband had severe pain on inspiration, resulting in respiratory insufficiency requiring assisted ventilation. His wife was treated with intravenous fluids and mannitol. Following the acute episode, the husband complained of more frequent headaches, and his wife continued to experience tearing eyes, easy fatigability, and pruritus after eating seafood.
Patient 6. On August 8, an 87-year-old U.S.-born man vomited 30 minutes after eating one third of a fried buffalo fish. Twenty-one hours later, he awoke with extreme stiffness and generalized muscle tenderness. At a local emergency department, his CK was 2226 IU/L with a CK-MB of 2.1%. The patient was treated with intravenous fluids and analgesics. Following this episode, the patient suffered 6 months of muscle weakness, primarily in his legs.
The origin of the buffalo fish eaten by patients 1, 2, 3, and 6 was traced to the same wholesaler in Louisiana who receives fish from approximately 25 fishermen who fish rivers in Louisiana. The fish for patients 4 and 5 were caught within a 100-mile radius of St. Louis, Missouri. The Food and Drug Administration is attempting to identify a toxin from recovered fish samples. The case histories suggest that the toxin is heat stable; no particular mode of preparation seems to increase risk for disease.
Reported by: K Kloss, MD, DePaul Health Center; L Feltmann, St. Louis County Health Dept, St. Louis; D Dodson, HD Donnell, Jr, MD, State Epidemiologist, Missouri Dept of Health. S Eyherabide, Mercy Healthcare, BA Jinadu, MD, Kern County Dept of Public Health, Bakersfield; AK Parikh, MD, Cedar Sinai Medical Center; M Tormey, MPH, L Mascola, MD, Los Angeles County Dept of Health Svcs, Los Angeles; GC Lawrence, Food and Drug Br, B Werner, MD, S Waterman, MD, State Epidemiologist, California State Dept of Health Svcs. RW Dickey, PhD, Food and Drug Administration, Dauphin Island, Alabama. N Sass, PhD, M Robl, DVM, Div of Toxicological Research, Food and Drug Administration, Laurel, Maryland. S Musser, PhD, Instrumentation and Biophysics Br, Food and Drug Administration, Washington, DC. D Altwein, PhD, Seattle District Laboratory, Seattle; J Hungerford, PhD, L Leja, Seafood Products Research Center, Food and Drug Administration, Bothell, Washington. E Mouzin, MD, Pasteur Institute, Paris, France. Foodborne and Diarrheal Diseases Br, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; Div of Applied Public Health Training, Epidemiology Program Office; and an EIS Officer, CDC.
Editorial Note: During the 1920s, the name "Haff disease" was given to an illness characterized by severe muscle pain and stiffness that affected approximately 1000 persons living along the Koenigsberg Haff, a brackish inlet of the Baltic Sea (1). Subsequent similar outbreaks were identified in Sweden and the former Soviet Union (2-4). Although the etiology was not determined, epidemiologic investigations linked illness to ingestion of fish, especially burbot.
The first reported case of Haff disease in the United States occurred in Texas in 1984 (M. Tormey, Los Angeles Department of Health Services, personal communication, 1997); five additional cases were reported in California during 1984-1986. All U.S. cases have been associated with eating buffalo fish.
Haff disease typically presents as a paroxysm of rhabdomyolysis, with accompanying muscle tenderness, rigidity, and dark brown urine. However, as in patient 3, milder presentations also occur. Although the median incubation period for the patients in this report was 8 hours (range: 6-21 hours), symptoms generally appear approximately 18 hours after eating fish.
Laboratory features of Haff disease include a markedly elevated CK level with an MB fraction of less than 5%. Levels of other muscle enzymes (e.g., lactate dehydrogenase, glutamate oxalate transaminase, and glutamate pyruvate transaminase) also are elevated. Myoglobinuria is often mistaken for gross hematuria (5). Diagnosis is based on a compatible clinical history.
Treatment is supportive and consists of administering large volumes of fluid early in the course of illness to prevent myoglobin toxicity to the renal tubules (5). Possible complications include electrolyte disturbances, renal failure, and disseminated intra-vascular coagulation. Symptoms usually resolve within 2-3 days. Historically, the case-fatality rate is approximately 1% (1).
Clinicians and public health practitioners are encountering an increasing variety of foodborne illnesses, in part because of a diversification of food preparation and eating habits. International travelers, members of ethnic groups with unique cuisines, and consumers of both imported and domestic specialty food items may be at risk for foodborne illnesses that are rare or have not been reported previously in the United States. Clinicians should be aware of food exposures that pose a risk to their patients and routinely obtain food histories, even from those patients whose illness may not appear to be food-related.
Physicians who identify or suspect cases of Haff disease, based on the clinical presentation, laboratory parameters, and food history, should report them to public health authorities for initiation of traceback and recall of implicated food items. State health departments are requested to report to the Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, CDC, telephone (404) 639-2206.
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