Haff disease is the development of rhabdomyolysis (swelling and breakdown of skeletal muscle, with a risk of acute kidney failure) within 24 hours of ingesting fish.^[1]

The first case of Haff disease was reported in 1924 in the vicinity of Königsberg on the Baltic coast, in people staying around the haff; hence the name “Haff disease”. From 1925 to 1940, about 1000 cases were reported not only in humans, but in birds and cats as well, and were linked to the consumption of fish (burbot, eel, and pike). Only twenty-six cases of Haff disease were reported in the US from 1984 to 2014.^[2]  As the standards of living are improving, the availability of fish for consumption is increasing, and thus, resulting in an increased number of cases.  

Haff disease is a rare clinical syndrome, the pathophysiology of which remains unclear. Palytoxin, a heat-stable toxin with thiaminase activity, has been proposed to play a role in the development of this condition. Due to the heat-stable nature of this toxin, it cannot be inactivated by cooking.

The etiology of Haff disease remains unclear, and further investigations are required.

Haff disease causes rhabdomyolysis and must be differentiated from other causes of rhabdomyolysis, which may be categorized as physical, non-physical, and genetic factors. Physical factors include trauma, excessive muscular activity, status epilepticus, high-grade fever, heatstroke, and electric shock. Non-physical factors include medications, infections, drugs, and electrolyte abnormalities. Genetic factors consist of autoimmune diseases, metabolic diseases, and various inherited conditions.

Cases of Haff disease are seen worldwide, but the causative organisms vary with the geographical location. Burbot, pike, freshwater eel, and whitefish are predominant causative fish in Eastern Europe and Sweden. Cases of Haff disease in China were related to freshwater pomfret and crayfish. In Japan, boxfish was associated with Haff disease and in the United States buffalo fish, crayfish and atlantic salmon were the culprits.

The major risk factor associated with Haff disease is consumption of aquatic foods (e.g., crayfish, burbot, buffalo fish).

Haff disease has an incubation period of eight hours and presents with nausea, vomiting, muscle rigidity, chest pain, diaphoresis, and brown urine (myoglobinuria). Though it is a self-limiting condition with a good prognosis, some cases may develop complications such as acute kidney injury and disseminated intravascular coagulation.

Symptoms of Haff disease develop within 24 hours of consumption of cooked seafood. These symptoms include nausea, vomiting, myalgia, muscle rigidity, chest pain, diaphoresis, dyspnea, and brown urine.

On examination there may be muscle tenderness, weakness, as well as myoglobinuria.

The diagnostic criteria for defining a case of Haff disease include a history of consumption of cooked seafood within 24 hours prior to the onset of symptoms, elevated serum CPK, and CK-MB fraction of less than 5%.

Evaluation of Haff disease should include CBC, creatine kinase, serum electrolytes, liver function tests, urine pH, and urinalysis.

Haff disease may result in cardiac arrhythmias due to hyperkalemia and hypocalcemia, as a result of rhabdomyolysis. Therefore, it is essential to monitor the patient with an ECG.

Hypoechoic areas due to inflammation of the muscles as well as fluid infiltration may be seen in Haff disease.

Other diagnostic studies are not required for the diagnosis of Haff disease.

The medical therapy of Haff disease consists of managing rhabdomyolysis by aggressive fluid hydration, managing electrolyte abnormalities (hyperkalemia and hypocalcemia), and other supportive care.

There is no surgical treatment indicated for Haff disease.

The primary prevention of Haff disease is avoiding the consumption of seafood that is associated with Haff disease.

The first case of Haff disease was reported in 1924 in the vicinity of Königsberg on the Baltic coast, in people staying around the haff; hence the name “Haff disease”. From 1925 to 1940, about 1000 cases were reported not only in humans, but in birds and cats as well. These cases were linked to the consumption of fish (burbot, eel, and pike). Only twenty-six cases of Haff disease were reported in the US from 1984 to 2014.^[1]  As the standards of living are improving, the availability of fish for consumption is increasing, and thus, resulting in an increased number of cases.  

• It was first described in 1924 in the vicinity of Königsberg on the Baltic coast, in people staying around the haff (German: lagoon).^[2]

• Over the subsequent fifteen years, about 1000 cases were reported in people, birds, and cats, usually in the summer and fall. A link was made with the consumption of fish (burbot, eel and pike). Since that time, only occasional reports have appeared of the condition, mostly from the Soviet Union and Germany.

• In 1997, six cases of Haff disease were reported in California and Missouri, all after the consumption of buffalo fish (Ictiobus cyprinellus).^[3] The source of the fish was traced by the Centers for Disease Control and Prevention. Studies of other fish from the same sources showed a hexane-soluble (and hence non-polar lipid) substance that induced similar symptoms in mice; other food-borne poisons commonly found in fish could not be detected.

Haff disease is a rare clinical syndrome, the pathophysiology of which remains unclear. Palytoxin, a heat-stable toxin with thiaminase activity, has been proposed to play a role in the development of this condition. Due to the heat-stable nature of this toxin, it cannot be inactivated by cooking.

• Palytoxin has been proposed as a disease model.^[1]

• It has been suggested that the toxin may have thiaminase activity (i.e. it degrades thiamine, also known as vitamin B1).^[2]

The etiology of Haff disease remains unclear and further investigations are required.

The etiology of Haff disease remains unknown. Further investigations and studies are required to determine whether cooked seafood contains an unknown heat-stable, tissue specific toxin that causes rhabdomyolysis, or if the cooked seafood activates a particular signaling pathway which is responsible for inducing rhabdomyolysis.^[1]

Haff disease causes rhabdomyolysis and must be differentiated from other causes of rhabdomyolysis, which may be categorized as physical, non-physical, and genetic factors. Physical factors include trauma, excessive muscular activity, status epilepticus, high-grade fever, heatstroke, and electric shock. Non-physical factors include medications, infections, drugs, and electrolyte abnormalities. Genetic factors consist of autoimmune diseases, metabolic diseases, and various inherited conditions.

Haff disease is known to cause rhabdomyolysis, and therefore, it should be differentiated from other causes of rhabdomyolysis. There are numerous etiologies of rhabdomyolysis and they may be categorized based on the physical, non-physical, and genetic factors.^[1]

• Trauma
• Excessive muscular activity
• Status epilepticus
• High-grade fever
• Heat stroke
• Electric shock

• Medication (e.g., anti-retrovirals, anti-histamines, anti-psychotics, antidepressants, and statins)
• Infection (bacterial and viral)
• Drugs (e.g., alcohol, heroin, cocaine, methamphetamine, ecstasy, and LSD)
• Electrolyte abnormalities (e.g., hypokalemia, hypophosphatemia, hyponatremia, and hypernatremia)

• Autoimmune diseases (e.g., polymyositis and dermatomyositis)
• Metabolic diseases (e.g., diabetes, thyroid dysfunction, primary hyperaldosteronism, primary adrenal insufficiency, central diabetes insipidus, postpartum hypernatremia, and pituitary dysfunction).
• Inherited conditions (e.g., glycogen storage disorders, fatty acid oxidation disorders, mitochondrial myopathies, muscular dystrophies, and RYR1- related myopathies)

Cases of Haff disease are seen worldwide, but the causative organisms vary with the geographical location. Burbot, pike, freshwater eel, and whitefish are predominant causative fish in Eastern Europe and Sweden. Cases of Haff disease in China were related to freshwater pomfret and crayfish. In Japan, boxfish was associated with Haff disease, and in the United States, buffalo fish, crayfish, and Atlantic salmon were the culprits.

Initially, more than 1000 cases were linked to the consumption of various species of cooked freshwater fish including burbot, pike, freshwater eel, and whitefish in Eastern Europe and Sweden. In China, cases of Haff disease were reported following consumption of cooked freshwater pomfret and boiled crayfish. Cases in Japan were linked to the consumption of cooked or raw boxfish. In the United States, 29 cases of Haff disease were reported following the consumption of buffalo fish, crayfish, and Atlantic salmon.^[1]

The major risk factor associated with Haff disease is consumption of aquatic foods (e.g., crayfish, burbot, buffalo fish).

The risk factor predisposing individuals to the development of Haff disease is consumption of aquatic foods (e.g., crayfish, burbot, buffalo fish).^[1]

Haff disease has an incubation period of eight hours and presents with nausea, vomiting, muscle rigidity, chest pain, diaphoresis, and brown urine. Though it is a self-limiting condition with a good prognosis, some cases may develop complications such as acute kidney injury and disseminated intravascular coagulation.

• As Haff disease is a rare clinical syndrome, it is oftentimes misdiagnosed. Early diagnosis and treatment are required to prevent the development of complications.

• It has an incubation period of eight hours and presents with nausea, vomiting, myalgias, muscle rigidity, chest pain (mimicking myocardial infarction), diaphoresis, dyspnea, and brown urine indicating myoglobinuria. As it is a self limiting condition with good prognosis, most patients recover in 2-5 days. Haff disease is rarely associated with mortality, but some cases may develop complications such as acute kidney injury and disseminated intravascular coagulation. ^{[1] [2]}