The etiology and autopsy findings in Colchicine intoxication-related deaths

Abstract

Colchicine is a drug which has a very narrow therapeutic range. This drug has been commonly used for Familial Mediterranean Fever (FMF), Behçet's disease, gout arthritis and acute pseudo gout attacks. In this study, the investigation reports and autopsy reports written by the Council of Forensic Medicine of Ankara between the years 2010-2014 were retrospectively analyzed to find out presence in the cases related to colchicine. Six cases were identified as colchicine intoxication, while three of them used colchicine for medical purpose. In four cases, colchicine was found to have been used for suicidal purpose. Among these four cases, two used colchicine for treatment. In all of our cases, colchicine was detected in bile specimen. Alveolar pulmonary edema and petechial hemorrhage were observed in the lung in all cases. Colchicine was detected in blood in four of the cases. In two cases, the concentration was found to be in therapeutic ranges (0,012 mg/L and 0,018 mg/L), while the other two, in lethal levels (0.099 mg/L and 0,264 mg/L). The most frequent histopathological finding is alveolar pulmonary edema in colchicine intoxication autopsies. Colchicine is widely used alkaloid drugs with narrow therapeutic ranges. More than 0.8 mg / kg in the acute high dose has usually fatal effects. The deaths resulted from colchicine intoxication are mainly suicide-oriented. Similar to other suicides with medicines, they are common among women. In our cases, colchicine was used for intention of suicide in four incidents (66, 66%).

Numerous mitotic figures with metaphase arrest in the mucosa suggest colchicine poisoning

“…Although plasma colchicine levels were not correlated with disease severity, the lethal blood concentration is reportedly between 0.021 and 0.25 mg/L. 2 Initial symptoms of colchicine poisoning include gastrointestinal complaints, such as abdominal pain, diarrhea, and nausea, which may resemble those of severe enterocolitis. 1 These symptoms rapidly progress to multiorgan failure with hypovolemic shock and bone marrow suppression.…”

“…After deacetylation, 10%-20% of colchicine is excreted through the kidneys, whereas the remaining quantity is excreted as bile. 2,3 The narrow therapeutic-toxicity window of colchicine placed patients with hepatic or renal dysfunction at high risk. Furthermore, CYP3A4 inhibitors, such as macrolides, calcium channel blockers, and calcineurin inhibitors, can decrease colchicine metabolism and increase the risk of colchicine poisoning.…”