Haff disease in the pandemic COVID-19 period in Brazil

Objective: This study describes and characterize the cases of Haff disease reported in Brazil during the COVID-19 pandemic period. Descriptive and cross-sectional study using public data from the National Center for Strategic Information and Response in Health Surveillance nacional. The Risk Communication number 17 of 09/15/2021 was accessed. The description of suspected cases was extended to all Brazilian states where notifications occurred, from January 1, 2020, to September 15, 2021. There was an increase in cases of Haff's disease in Brazil, from 2020 onwards, with 46 in the Northeast region of Brazil. Eighty-five cases and three deaths were reported between January and September 2021 in the North, Northeast, South and Midwest regions. Most cases occurred in regions of greater heat such as the coastal region of the Northeast and around regions of the Amazon River Basin. A critical period for coping with the SARS-CoV-2 virus pandemic in Brazil, cases of disease of Haff could be reported in various regions of country. Despite the etiological suspicions, studies, and follow-up of the cases, it is still not possible to affirm that the disease is caused by biomolecules of the Palytoxin-Like Toxins group. The possible identification of the responsible toxin(s) will be essential for a complete understanding of the etiopathogenic mechanism of the disease and adequate development of prevention, treatment, and cure measures.

Ionophore Toxin Maduramicin Produces Haff Disease-Like Rhabdomyolysis in a Mouse Model

Maduramicin is a toxic ionophore antibiotic that is isolated from Streptomyces, frequently occurring in an aquatic environment. To understand the potential role of maduramicin in crayfish consumption related Haff disease, a mouse model was established in this study. Two exposure routes of maduramicin in the abdominal muscle and the hepatopancreas tissue homogenates of crayfish were given intragastrically to mice in different doses for seven days. Action changes, clinical symptoms, feed consumption, body weight, blood biochemistry, and histopathology examination of mice were observed and analyzed. In the natural exposure group, relatively low concentration of maduramicin in crayfish muscle and hepatopancreas had no obvious effects on mental state, body weight, blood biochemical indexes, or histologic appearance. However, in the artificial exposure group, with increasing concentrations, maduramicin in crayfish muscle and hepatopancreas homogenates both induced mental sluggishness and weight loss of mice. Blood biochemical examination showed that 3.5 mg·kg−1 and 7 mg·kg−1 maduramicin in crayfish tissue homogenates significantly increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and creatine kinase (CK). Additionally, histopathological examination showed that multiple organs were damaged by maduramicin, including degeneration of liver cells, shedding of renal epithelial cells, and disturbance and partial lysis of myocardial and skeletal muscle filaments in the mice. In summary, maduramicin may not cause Haff disease through contamination of the aquatic environment under normal conditions. Maduramicin can be used as a potential toxin tool to establish a rhabdomyolysis disease animal model for drug development.

Efficacy of Active Charcoal and Mannitol in Patients with Haff Disease Caused by the Consumption of Crayfish (Procambarus clarkii): A Retrospective Cohort Study

This study evaluates the clinical efficacy of activated charcoal combined with mannitol (ACM) for the treatment of Haff disease. This is a retrospective cohort study conducted at the Emergency Department of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. Consecutive patients who were hospitalized during a two-year time frame (from June 2016 to August 2017) and diagnosed with Haff disease were reviewed. Clinical symptoms, laboratory findings, pain/anxiety scores, and treatment-related adverse events were collected. Sixty-eight Haff disease patients after boiled crayfish consumption were enrolled in this study. Besides standard treatments for Haff disease, 22 patients had an oral administration of activated charcoal and mannitol within 12 hours of hospital admission (ACM group), while the other 46 patients did not receive such treatment (non-ACM group). Baseline characteristics including clinical symptoms, serum enzyme levels, and pain/anxiety scores were comparable between the two groups. Activated charcoal and mannitol treatment led to lower CK-MB and AST levels from 12 hours to 60 hours, lower ALT and LDH levels from 12 hours to 72 hours, and lower CK levels from 24 hours to 72 hours after hospitalization. Patients in the ACM group had significantly shortened duration of hospital stays (7.5 [6.0–8.0] days vs 8.0 [6.8–10.0] days, p=0.032) and lower anxiety scores 24 hours after hospital admission (40.7 ± 4.9 vs 44.1 ± 6.3, p=0.032) than in the non-ACM group. No patient experienced treatment-related adverse events. The overall prognosis of both groups is good. Among patients with Haff disease caused by boiled crayfish, activated charcoal combined with mannitol treatment resulted in shorter hospital stays, lower serum CK, CK-MB, AST, ALT, and LDH levels, and lower anxiety scores.

From quail to earthquakes and human conflict: a historical perspective of rhabdomyolysis

Rhabdomyolysis is a common cause of acute kidney injury, featuring muscle pain, weakness and dark urine and concurrent laboratory evidence of elevated muscle enzymes and myoglobinuria. Rhabdomyolysis is often seen in elderly and frail patients following prolonged immobilization, for example after a fall, but a variety of other causes are also well-described. What is unknown to most physicians dealing with such patients is the fascinating history of rhabdomyolysis. Cases of probable rhabdomyolysis have been reported since biblical times and during antiquity, often in the context of poisoning. Equally interesting is the link between rhabdomyolysis and armed conflict during the 20th century. Salient discoveries regarding the pathophysiology, diagnosis and treatment were made during the two world wars and in their aftermath. ‘Haff disease’, a form of rhabdomyolysis first described in 1920, has fascinated scientists and physicians alike, but the marine toxin causing it remains enigmatic even today. As a specialty, we have also learned a lot about the disease from 20th-century earthquakes, and networks of international help and cooperation have emerged. Finally, rhabdomyolysis has been described as a sequel to torture and similar forms of violence. Clinicians should be aware that rhabdomyolysis and the development of renal medicine are deeply intertwined with human history.