To the Editor:
Exercise and nutrition are essential to good health. However, exercise combined with the consumption of risky food or drugs can cause serious illness.
A 41-y-old man who had been receiving simvastatin therapy (40 mg·d-1) for dyslipidemia for a few years presented to the emergency department of Maharaj-Nakhornsrithammaraj Hospital because of a 2-d history of generalized myalgia and weakness. The patient had been on a mountain trek with 3 companions for 1 d and had ingested freshwater fish that they had caught for dinner (Figure 1 and 2). The patient had eaten the largest portion and developed nausea in 30 min and shortness of breath, muscle pain, and weakness approximately 5 h after the meal. The next morning, the patient was unable to walk and had little urine, which was dark brown in color. The 3 companions who shared the dinner also had nausea and vomiting in 30 min and myalgia approximately 5 to 6 h after the meal; however, their symptoms were self-limited and resolved the following morning.
The cooked fish meal that was consumed by the patient during a trekking trip on a mountain in southern Thailand. Image used with permission from the patient.
The patient’s companions required 2 d to carry him down the mountain using a bamboo stretcher, which also constituted vigorous exercise. The patient denied fever, new medications, recreational drug use, recent illness, trauma, or other vigorous exercise. He was conscious, fatigued, and tachypnic on arrival. His temperature was 36.7°C; heart rate was 100 beats·min-1, blood pressure was 127/70 mm Hg, respiratory rate was 36 beats·min-1, and oxygen saturation was 98% on room air. Physical examination revealed tenderness in both thighs and the shoulder area and generalized weakness. Electrocardiography revealed sinus tachycardia with tall peak T waves. Laboratory results demonstrated hyperkalemia and elevated creatinine, urea, and creatine phosphokinase levels (Table 1). Urine myoglobin analysis was unavailable. The patient’s companions also had elevated creatine phosphokinase levels of 1235, 1728, and 490 U·L-1 (normal range, 24–195 U·L-1).
Laboratory parameters and volume status during hospitalization
The patient was diagnosed as having rhabdomyolysis, acute kidney injury, and hyperkalemia. He received intravenous fluid and standard treatment for hyperkalemia. However, he remained oliguric despite adequate fluid replacement, and his renal function declined. On hospital Day 3, he developed severe dyspnea owing to volume overload. He was intubated and underwent hemodialysis. He improved clinically and was extubated on Day 7. The patient required intermittent hemodialysis for 3 wk and was discharged uneventfully on Day 34. He had no further symptoms during the 2-wk post-discharge follow-up, at which time his serum creatinine level was 1.8 mg·dL-1.
The primary cause of the rhabdomyolysis was considered to be fish ingestion, a condition often known as Haff disease, which in this case was potentially precipitated by vigorous exercise (mountain trekking) and simvastatin ingestion. He was thus diagnosed on the basis of following rationale. First, all his companions, who ingested the same fish meal, also had clinical and elevated creatine phosphokinase levels of 1235, 1728, and 490 U·L-1. Second, a temporal relationship exists between the fish ingestion and the illness experienced by all who had eaten the fish because gastrointestinal symptoms occurred within 30 min and myalgia developed in approximately 5 h. Finally, the biological plausibility of the soro brook carp, Neolissochilus soroides (family Cyprinidae) (Figure 2), causing rhabdomyolysis, as previously reported after consumption of other cyprinids, was also considered. 1 Statin-induced rhabdomyolysis is more common than Haff disease. The reported incidence of statin-associated muscle symptoms varies greatly, ranging from 5 to 29%, with milder symptoms being common and more serious symptoms being rarer. However, rhabdomyolysis is far rarer, with an incidence of approximately 1 in 10,000 population. 2 Elevated risk of statin-related muscle adverse events can be attributed to various genetic backgrounds. 3 Therefore, the patient may have had higher risk of statin-induced rhabdomyolysis owing to his Asian ethnicity and excessive exercise. 4 However, he had used the same dose of simvastatin and previously trekked to the same extent without developing rhabdomyolysis. In addition, a detailed history review found that the patient and his companions had no underlying diseases for which trekking is considered a serious predisposing risk factor. 5 We hypothesized that compared with his companions, the patient had severe rhabdomyolysis due to consuming the most fish and taking simvastatin.
Neolissochilus soroides, a freshwater fish, which is called Rangaea in the local language. Image used with permission from the patient.
Haff disease, named after the Königsberg Haff, which lies along the Baltic coast, was first reported in 1924 and recurred in periodic clusters. 6 Comparison of features of confirmed cases of the disease in the United States and China during the reporting period, 1997 to 2014, revealed that the median incubation period was 8 h for the United States, ranging from 3 to 21 h, and 7 h for China, ranging from 0.1 to 41 h. The major symptoms are muscle pain and stiffness. Other symptoms are nausea or vomiting, stomachache, diarrhea, headache, chest pain, shortness of breath, sweating, and pain to light touch. 7 Haff disease is associated with various types of fish, such as carp, crayfish, pomfret, freshwater eel, and marine boxfish. No information has been reported about which part of the fish contains more toxins than others. The toxins are heat stable and cannot be recognized by smell or taste. Currently, the toxin and etiology of the disease have not been identified. 8 Treatment is mainly supportive and standard care for rhabdomyolysis and its complications. 9
Haff disease is not widely recognized, so it is understandably underreported. A high index of suspicion and exclusion of other causes are important parts of the diagnosis. Trekkers should not consume fish from mountain waterfalls because they can cause Haff disease. In addition, foraging wildlife has a negative impact on the ecosystem.