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Colchicine Poisoning

Colchicine Toxicity

Colchicine is a lipophilic drug used to treat various conditions, including gout, primary biliary cirrhosis, familial Mediterranean fever, and several other disorders. It possesses a very narrow therapeutic index that predisposes to poisoning. Patients initially present with gastrointestinal complaints followed by multiorgan failure (the liver, heart, and kidneys are mainly affected) and bone marrow suppression that leads to sepsis. The diagnostic workup must confirm the recent use of this drug, whereas a full laboratory workup is necessary to determine the extent of organ damage.


Presentation

The clinical presentation of colchicine poisoning stems from the potent effects of the drug [1] [2] [3]. Colchicine disrupts the assembly of microtubules and higher doses can promote severe disruption of various cellular mechanisms [1] [3] [4]. The majority of studies describe colchicine poisoning in three phases [1] [2] [5]:

Fever
  • The use of colchicine was due to diagnosis of Familial Mediterranean fever (FMF) in the families of 8 patients, diagnosis of Behçet disease in 1 patient's father, diagnosis of Behçet disease in 1 patient herself, and diagnosis of FMF in 6 patients themselves[ncbi.nlm.nih.gov]
  • Colchicine is a lipophilic drug used to treat various conditions, including gout, primary biliary cirrhosis, familial Mediterranean fever, and several other disorders. It possesses a very narrow therapeutic index that predisposes to poisoning.[symptoma.com]
  • Some patients report a burning feeling in the mouth and throat, and develop a fever. Kidney failure can onset, along with severe internal bleeding. Treatment for colchicine poisoning focuses on supportive therapy to keep the patient alive.[wisegeek.net]
  • INTRODUCTION: Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF).[ncbi.nlm.nih.gov]
Weakness
  • Multi-organ damage phase - Considered as the critical period of colchicine poisoning, the first week is characterized by the onset of severe and progressive muscle weakness accompanied by failure of several organs, including the kidneys, liver, and bone[symptoma.com]
  • Some patients develop neuromyopathy (mild to severe myalgia, muscle weakness, numbness and fatigue) with chronic dosing, mostly without GI symptoms.[dpic.org]
  • Other side effects of Colchicine include: Fatigue Weakness Sore throat Rash Numbness Allergic reactions such as hives, swelling of lips/face/tongue, closing of throat, difficulty breathing Unsuspected bleeding and brusing More serious Colchicine side[resource4thepeople.com]
  • The drug has a wide range of applications: used not only in the treatment of weak erection and premature ejaculation, but also to improve potency and endurance of the reproductive system, increase the duration of sexual intercourse.[vumxxdo.gq]
  • […] tell their doctor and pharmacist about all the medicines they take, and to check before taking any new medicines stop taking colchicine and see their doctor if they develop nausea, vomiting or diarrhoea; unusual bleeding or bruising; muscle pain or weakness[nps.org.au]
Anemia
  • Fatigue Weakness Sore throat Rash Numbness Allergic reactions such as hives, swelling of lips/face/tongue, closing of throat, difficulty breathing Unsuspected bleeding and brusing More serious Colchicine side effects include fetal damage in pregnant women anemia[resource4thepeople.com]
  • More seriously, Colchicine can reduce the white blood cells count, damage bone marrow and lead to anemia (lower than normal number of red blood cells / not enough hemoglobin).[mypeyronies.com]
Fatigue
  • Some patients develop neuromyopathy (mild to severe myalgia, muscle weakness, numbness and fatigue) with chronic dosing, mostly without GI symptoms.[dpic.org]
  • Other side effects of Colchicine include: Fatigue Weakness Sore throat Rash Numbness Allergic reactions such as hives, swelling of lips/face/tongue, closing of throat, difficulty breathing Unsuspected bleeding and brusing More serious Colchicine side[resource4thepeople.com]
Intravenous Administration
  • CLINICAL FEATURES: Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after[ncbi.nlm.nih.gov]
Sore Throat
  • Other side effects of Colchicine include: Fatigue Weakness Sore throat Rash Numbness Allergic reactions such as hives, swelling of lips/face/tongue, closing of throat, difficulty breathing Unsuspected bleeding and brusing More serious Colchicine side[resource4thepeople.com]
  • The next patient has a sore throat. House makes him wait. Cuddy comes in an examines the patient. House acts like he's surprised the patient has a sore throat. Cuddy sends the patient home to drink hot tea.[house.wikia.com]
Nausea
  • A 48-year-old male was admitted to hospital complaining of vomiting, nausea and diarrhea following ingestion of the plant and died in four days.[ncbi.nlm.nih.gov]
  • In toxic doses it produces nausea and vomiting, and bone marrow suppression often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects.[ncbi.nlm.nih.gov]
  • In toxic doses it produces nausea and vomiting and bone marrow suppression, often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects.[ncbi.nlm.nih.gov]
  • A 39-year-old man presented to the emergency room with nausea, vomiting, and diarrhea 9 hours after ingestion of wild garlic. Symptoms attributed to food poisoning, and he received supportive cares and discharged.[ncbi.nlm.nih.gov]
  • Patients with colchicine toxicity initially present with gastrointestinal symptoms of nausea, vomiting, diarrhea and abdominal pain.[calpoison.org]
Vomiting
  • A 48-year-old male was admitted to hospital complaining of vomiting, nausea and diarrhea following ingestion of the plant and died in four days.[ncbi.nlm.nih.gov]
  • In toxic doses it produces nausea and vomiting, and bone marrow suppression often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects.[ncbi.nlm.nih.gov]
  • In toxic doses it produces nausea and vomiting and bone marrow suppression, often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects.[ncbi.nlm.nih.gov]
  • A 39-year-old man presented to the emergency room with nausea, vomiting, and diarrhea 9 hours after ingestion of wild garlic. Symptoms attributed to food poisoning, and he received supportive cares and discharged.[ncbi.nlm.nih.gov]
  • Patients with colchicine toxicity initially present with gastrointestinal symptoms of nausea, vomiting, diarrhea and abdominal pain.[calpoison.org]
Diarrhea
  • A 48-year-old male was admitted to hospital complaining of vomiting, nausea and diarrhea following ingestion of the plant and died in four days.[ncbi.nlm.nih.gov]
  • A 39-year-old man presented to the emergency room with nausea, vomiting, and diarrhea 9 hours after ingestion of wild garlic. Symptoms attributed to food poisoning, and he received supportive cares and discharged.[ncbi.nlm.nih.gov]
  • Patients with colchicine toxicity initially present with gastrointestinal symptoms of nausea, vomiting, diarrhea and abdominal pain.[calpoison.org]
  • The majority of studies describe colchicine poisoning in three phases: Gastrointestinal phase - Within the first day following the ingestion of higher doses, the first symptoms appear, including diarrhea, nausea, vomiting, and abdominal pain, mimicking[symptoma.com]
  • Possible side effects of taking this drug include vomiting, nausea, stomach pain and diarrhea [1, 2, 3, 4]. How much is Colchicine Toxicity? The exact Colchicine dose that causes toxicity symptoms is still unknown.[overdoseinfo.com]
Abdominal Pain
  • The majority of studies describe colchicine poisoning in three phases: Gastrointestinal phase - Within the first day following the ingestion of higher doses, the first symptoms appear, including diarrhea, nausea, vomiting, and abdominal pain, mimicking[symptoma.com]
  • Patients with colchicine toxicity initially present with gastrointestinal symptoms of nausea, vomiting, diarrhea and abdominal pain.[calpoison.org]
  • Early symptoms include abdominal pain, nausea, vomiting and diarrhoea. Symptoms occurring after 1 to 7 days include: confusion, cardiac, renal and hepatic impairment, respiratory distress, hyperpyrexia and bone marrow depression.[medsafe.govt.nz]
  • Mary Louise Yoder Milman said an overdose of the substance would cause abdominal pain, nausea and vomiting at first, and then lead to confusion, a drop in blood pressure, shock, respiratory distress, kidney failure and eventually cardiovascular collapse[syracuse.com]
  • The patient may manifest with diarrhea, vomiting, nausea, abdominal pain and a significant loss of fluid. Peripheral leukocytosis may also be seen in patients. The second stage may happen around 24-72 hours after the ingestion.[overdoseinfo.com]
Acute Abdomen
  • One of patients showed total alopecia, one showed leucocytosis, and another one showed acute abdomen picture. None of the patients showed mortality. CONCLUSIONS: Mortality of colchicine toxicity is high and quick assessment is absolutely required.[ncbi.nlm.nih.gov]
Hypotension
  • Delayed symptoms of colchicine toxicity include seizures, cardiac dysrhythmias, hypotension, shock, coagulopathy, pancytopenia and respiratory, renal, and hepatic failure.[calpoison.org]
  • Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).[ncbi.nlm.nih.gov]
  • In the ED, she had epigastric pain, nausea, and hypotension, which can develop in stage 1 of colchicine intoxication.[kjccm.org]
  • In our case the compensatory excretion was not possible since the patient's chronic renal insufficiency was additionally deteriorated by hypotension, hypoxia and rhabdomyolysis due to the colchicine effect on muscle cells.[ccforum.biomedcentral.com]
Myopathy
  • Neuropathy and myopathy are also described in many patients, particularly in cases of chronic ingestion of subtoxic or toxic doses.[symptoma.com]
  • Clinical features, pathophysiology, and treatment of polymyositis and dermatomyositis; inclusion body myositis; metabolic myopathies; drug-induced myopathies; muscular dystrophies and neurologic diseases; laboratory testing and imaging; electrophysiological[books.google.com]
  • Co-administration with statins may increase the risk of myopathy. MECHANISMS OF TOXICITY: Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network.[ncbi.nlm.nih.gov]
  • […] considered as second-line therapy of gout because it has a narrow therapeutic window and a high rate of side effects. [4] The main untoward effects of colchicine include nausea, vomiting, diarrhoea, and abdominal pain, bone marrow suppression and proximal myopathy[indianjnephrol.org]
Alopecia
  • One of patients showed total alopecia, one showed leucocytosis, and another one showed acute abdomen picture. None of the patients showed mortality. CONCLUSIONS: Mortality of colchicine toxicity is high and quick assessment is absolutely required.[ncbi.nlm.nih.gov]
  • For survivors, alopecia and leukocytosis occur in the third phase. Toxicity does not always occur in phases. GI symptoms can occur at any time.[dpic.org]
  • In stage 4, which begins 7 days after ingestion, generalized alopecia and rebound leukocytosis can be observed.[kjccm.org]
  • Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. (3) Recovery typically occurs within a few weeks of ingestion, but with rebound leucocytosis and alopecia. [5], [6] Acute renal failure in our patient might[indianjnephrol.org]
Eruptions
  • Improve your competency and readiness with the latest guidance on volcanic eruptions, extreme sports, splints and slings, wilderness cardiology, living off the land, aerospace medicine, mental health in the wilderness, tactical combat casualty care, and[books.google.com]
Confusion
  • We report a further case in which two persons confused this highly poisonous plant with wild garlic ( Allium ursinum ), a popular spice in the Central European cuisine.[maltawildplants.com]
  • Symptoms occurring after 1 to 7 days include: confusion, cardiac, renal and hepatic impairment, respiratory distress, hyperpyrexia and bone marrow depression.[medsafe.govt.nz]
  • It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians.[ncbi.nlm.nih.gov]
  • Mary Louise Yoder Milman said an overdose of the substance would cause abdominal pain, nausea and vomiting at first, and then lead to confusion, a drop in blood pressure, shock, respiratory distress, kidney failure and eventually cardiovascular collapse[syracuse.com]
  • Features after 1–7 days include confusion, decreased cardiac output, cardiac arrhythmias, renal and hepatic impairment, respiratory distress, hyperpyrexia, and bone-marrow depression.[gov.uk]
Seizure
  • Some studies also mention neurological symptoms (stupor, coma, seizures, or delirium), dysrhythmias, pancreatitis, and rhabdomyolysis.[symptoma.com]
  • Delayed symptoms of colchicine toxicity include seizures, cardiac dysrhythmias, hypotension, shock, coagulopathy, pancytopenia and respiratory, renal, and hepatic failure.[calpoison.org]
  • After the sedative drug (midazolam, 3 mg/hr.) used during the MV was discontinued, seizure-like movements were not observed.[kjccm.org]
Unresponsive to Pain Stimuli
  • On physical examination she was unresponsive to painful stimuli, skin was cool and dry, and pupils were midposition and not reactive. Bowel sounds were normal and lungs were clear bilaterally.[calpoison.org]
Kidney Failure
  • Kidney failure can onset, along with severe internal bleeding. Treatment for colchicine poisoning focuses on supportive therapy to keep the patient alive.[wisegeek.net]
  • Mary Louise Yoder Milman said an overdose of the substance would cause abdominal pain, nausea and vomiting at first, and then lead to confusion, a drop in blood pressure, shock, respiratory distress, kidney failure and eventually cardiovascular collapse[syracuse.com]
  • The tests show the antibiotics didn't cause the kidney failure. House informs them the patient is getting better. House tells Wilson he criticizes his fellows to make them feel terrible because it will make them better doctors.[house.wikia.com]
  • The urine showed signs of liver and kidney failure (stage 2), and died after the third day. The meadow was investigated, and there was evidence of grazing upon Colchicum autumnale.[naturespoisons.com]
Oliguria
  • He also complained oliguria on day 6. Patient's wife has brought the tuber. It was identified as G. superba. Patient revealed that he had consumed 250 g of the tuber along with water. Patient had no history of any illness.[indianjnephrol.org]
  • Oliguria and then anuria ensued and were not responsive to supportive measures. He continued to deteriorate and death occurred approximately 11 hours after admission.[emj.bmj.com]
Anuria
  • Oliguria and then anuria ensued and were not responsive to supportive measures. He continued to deteriorate and death occurred approximately 11 hours after admission.[emj.bmj.com]

Workup

Although the presentation of colchicine poisoning consists of nonspecific gastrointestinal and systemic symptoms, the physician must obtain a detailed patient history and conduct a thorough laboratory workup in order to narrow down the differential diagnosis. Colchicine is extensively metabolized in the liver (and in the kidneys to some extent), meaning that several drugs may enhance its effect, eg. statins, antimicrobial drugs (clarithromycin, erythromycin, and ketoconazole), cyclosporine, but also grapefruit juice [1] [7]. For this reason, medication history is particularly important for identifying possible poisoning due to colchicine [1]. After assessing the course and progression of symptoms, a comprehensive laboratory assessment is mandatory. Typical findings in colchicine poisoning are high creatine phosphokinase levels (CPK, or CK), lactic acidosis, azotemia (pre-renal), electrolyte imbalance, and abnormally high liver transaminases, whereas coagulopathies are also found in some cases [1] [2] [6]. Leukocytosis is seen in the initial stages, but severe leukopenia and pancytopenia are detected in the multi-organ damage phase, due to bone marrow suppression [2]. Electrophysiologic studies may be of use in the setting of an undisclosed diagnosis, showing specific patterns of motor unity myopathy in muscles of the trunk and the proximal limbs and complex repetitive discharges [5] [7].

Decreased Oxygen Saturation
  • We applied a non-rebreather mask because decreased oxygen saturation (89% via a nasal cannula on O 2 5 L/min) and tachypnea (23-35/min) were observed. On chest X-ray, bilateral lung field haziness was seen.[kjccm.org]

Treatment
  • This alkaloid found in Colchicum autumnale is used primarily in the treatment of gout.[ncbi.nlm.nih.gov]
  • There is no recognised antidote for colchicine poisoning and treatment is symptomatic. Fab fragments may have a promising future in eliminating colchicine from the body, but are currently not clinically available.[ncbi.nlm.nih.gov]
  • Colchicine is only indicated for intermittent use and patients will often initiate treatment themselves; therefore the potential exists for a severe drug interaction to occur.[medsafe.govt.nz]
  • He received treatments based on the diagnosis of acute gastroenteritis. The patient was in a fair condition during 30 hours of hospitalization until he suddenly developed respiratory distress and unfortunately died with cardiopulmonary arrest.[ncbi.nlm.nih.gov]
  • Mechanical ventilation, dopamine, noradrenaline, crystalloid solutions and fresh frozen plasma were applied but despite treatment the patient died five days after the ingestion.[ncbi.nlm.nih.gov]

Prognosis
  • It is characterized by multiorgan involvement and by poor prognosis associated with overdose. In this article we present four children with colchicine poisoning to emphasize that colchicine poisoning has a large spectrum in childhood.[ncbi.nlm.nih.gov]
  • Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.[ncbi.nlm.nih.gov]
  • Hepatic and renal dysfunction as well as certain drugs could worsen the prognosis of poisoning with colchicine.[ccforum.biomedcentral.com]
  • Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. (3) Recovery typically occurs within a few weeks of ingestion, but with rebound leucocytosis and alopecia. [5], [6] Acute renal failure in our patient might[indianjnephrol.org]
  • […] despite colchicine being rapidly absorbed because there is extensive enterohepatic recirculation. 8 Consequently, it is important that efforts are made to remove any remaining colchicine because the retrieval of even small amounts can greatly benefit prognosis[emj.bmj.com]

Etiology
  • The case can be confirmed if laboratory testing was not performed because either a predominant amount of clinical and nonspecific laboratory evidence of a particular chemical was present or the etiology of the agent is known with 100% certainty.[emergency.cdc.gov]

Epidemiology
  • IMMUNOTOXICANTS IN HUMAN BEINGS 296 SURVEILLANCE OF ATRISK HUMANS EXPOSED TO IMMUNOTOXICANTS 297 CLINICAL ASSESSMENT OF IMMUNOTOXICITY 298 CLINICAL IMMUNOLOGY ENDPOINTS TO ASSESS NONSPECIFIC IMMUNITY 300 IMMUNE ENDPOINTS ADOPTED BY THE ATSDR 301 ENVIRONMENTAL EPIDEMIOLOGY[books.google.com]
  • Probable : A clinically compatible case in which a high index of suspicion (credible threat or patient history regarding location and time) exists for colchicine exposure, or an epidemiologic link exists between this case and a laboratory-confirmed case[emergency.cdc.gov]
  • Epidemiology The primary use of colchicine is in the prevention and treatment of painful exacerbations of gouty arthritis.[calpoison.org]
  • Epidemiologic data are consistent with an increase in the prevalence of gout. Acute gouty arthritis most commonly begins with the involvement of a single joint in the lower ex-tremities (85 – 90% of cases), often the first metatarsophalangeal joint.[flipper.diff.org]
Sex distribution
Age distribution

Pathophysiology
  • Clinical features, pathophysiology, and treatment of polymyositis and dermatomyositis; inclusion body myositis; metabolic myopathies; drug-induced myopathies; muscular dystrophies and neurologic diseases; laboratory testing and imaging; electrophysiological[books.google.com]
  • Pathophysiology Colchicine’s effectiveness in treating gout is due to its ability to decrease the response of granulocytes and other inflammatory cells.[calpoison.org]
  • Medical Center Ljubljana, Ljubljana, Slovenia (5) Professor, Head, Center for Intensive Internal Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia (6) Associated Professor, Medical Faculty and Department for Cardiology, Institute for Pathophysiology[ccforum.biomedcentral.com]

Prevention
  • How to prevent Colchicine Toxicity? An overdose in colchicine can be prevented by following the prescription orders of the physician. Additional dosage of the drug must not be done without the knowledge of the physician.[overdoseinfo.com]
  • In those patients that survive the initial phase of poisoning, G-CSF offers an effective method of treating the pancytopenia and preventing overwhelming septicaemia. Daily monitoring of the patient's haematological status is strongly recommended.[ncbi.nlm.nih.gov]
  • Get the skills you need now with new information on global humanitarian relief and expedition medicine, plus expanded coverage of injury prevention and environmental preservation.[books.google.com]
  • There is no antidote or consistently effective therapy for colchicine toxicity so prevention is the key to avoiding colchicine toxicity and death.[dpic.org]
  • By binding to intracellular α- and β-tubulin, colchicine prevents the formation of microtubules[ 5 , 6 ] and leads to disruption of the microtubular network.[kjccm.org]

References

Article

  1. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010;48(5):407-414.
  2. Aghabiklooei A1, Zamani N, Hassanian-Moghaddam H, Nasouhi S, Mashayekhian M. Acute colchicine overdose: report of three cases. Reumatismo. 2014;65(6):307-311.
  3. Iosfina I, Lan J, Chin C, Werb R, Levin A. Massive Colchicine Overdose with Recovery. Case Rep Nephrol Urol. 2012;2(1):20-24.
  4. Maxwell MJ, Muthu P, Pritty PE. Accidental colchicine overdose: a case report and literature review. Emerg Med J. 2002;19:265–267.
  5. Ozdemir R, Bayrakci B, Teksam O. Fatal poisoning in children: acute colchicine intoxication and new treatment approaches. Clin Toxicol (Phila). 2011;49(8):739-743.
  6. Medani S, Wall C. Colchicine toxicity in renal patients - Are we paying attention? Clin Nephrol. 2016;86(2):100-105.
  7. Huh K, Joung JY, Jeong H, et al. Colchicine-induced myoneuropathy in a cyclosporine-treated renal transplant recipient. Kidney Res Clin Pract 2013;32(2):74-77.

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Last updated: 2019-06-28 10:59