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{{Short description|An article on Colchicine Poisoning and its effects on the body}}
{{Draft topics|medicine-and-health}}
{{AfC topic|other}}


'''Colchicine poisoning''' occurs due to the ingestion of ], a ] derived from the plant ], and can be life-threatening. '''Colchicine poisoning''' occurs due to the ingestion of ], a ] derived from the plant ], and can be life-threatening.


== Pathophysiology == == Pathophysiology ==
Colchicine's toxicity arises primarily from its mechanism of action, which involves binding to ] and disrupting ] formation, leading to impaired cellular processes. This disruption affects rapidly dividing cells, particularly in the ] and ], resulting in significant gastrointestinal symptoms such as ], ], and ] due to rapid turnover of intestinal mucosal cells. The drug is metabolized in the liver, primarily by ] enzymes, leading to the formation of several ], including 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC). These metabolites can exhibit increased toxicity compared to the parent compound, contributing to ] injury and other systemic effects. As colchicine inhibits ] by preventing ] formation, it leads to multi-organ dysfunction. The early phase (10-24 hours post-ingestion) is characterized by gastrointestinal distress and initial ]. In the subsequent phase (24 hours to 7 days), patients may experience severe complications including ], ] (DIC), and cardiac issues due to direct toxicity on cardiac myocytes. The high affinity of colchicine for tissues like the liver and kidneys contributes to its rapid accumulation in these organs, leading to further complications. <!-- Important, do not remove this line before article has been created. --> Colchicine's toxicity arises primarily from its mechanism of action, which involves binding to ] and disrupting ] formation, leading to impaired cellular processes. This disruption affects rapidly dividing cells, particularly in the ] and ], resulting in significant gastrointestinal symptoms such as ], ], and ] due to rapid turnover of intestinal mucosal cells.<ref name=":0">{{Cite journal |last1=Draa |first1=Elham |last2=Arebi |first2=Ali |last3=Alarabi |first3=Safwan |date=2022 |title=Colchicine poisoning: A case of deliberate self poisoning, late presentation and fatal outcome |journal=Ibnosina Journal of Medicine and Biomedical Sciences |language=en |volume=07 |issue=5 |pages=180–183 |doi=10.4103/1947-489X.210285 |doi-access=free |issn=1947-489X}}</ref><ref name=":1">{{Cite journal |last1=Finkelstein |first1=Yaron |last2=Aks |first2=Steven E. |last3=Hutson |first3=Janine R. |last4=Juurlink |first4=David N. |last5=Nguyen |first5=Patricia |last6=Dubnov-Raz |first6=Gal |last7=Pollak |first7=Uri |last8=Koren |first8=Gideon |last9=Bentur |first9=Yedidia |date=2010 |title=Colchicine poisoning: the dark side of an ancient drug |url=https://pubmed.ncbi.nlm.nih.gov/20586571/ |journal=Clinical Toxicology (Philadelphia, Pa.) |volume=48 |issue=5 |pages=407–414 |doi=10.3109/15563650.2010.495348 |issn=1556-9519 |pmid=20586571}}</ref> The drug is metabolized in the liver, primarily by ] enzymes, leading to the formation of several ], including 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC). These metabolites can exhibit increased toxicity compared to the parent compound, contributing to ] injury and other systemic effects.<ref>{{Cite journal |last1=Tateishi |first1=T. |last2=Soucek |first2=P. |last3=Caraco |first3=Y. |last4=Guengerich |first4=F. P. |last5=Wood |first5=A. J. |date=1997-01-10 |title=Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation |url=https://pubmed.ncbi.nlm.nih.gov/8960070/ |journal=Biochemical Pharmacology |volume=53 |issue=1 |pages=111–116 |doi=10.1016/s0006-2952(96)00693-4 |issn=0006-2952 |pmid=8960070}}</ref><ref>{{Cite journal |last1=Huang |first1=Ruoyue |last2=Duan |first2=Jingyi |last3=Huang |first3=Wen |last4=Cheng |first4=Yan |last5=Zhu |first5=Beiwei |last6=Li |first6=Fei |date= 2024|title=Inhibition of CYP1A1 Alleviates Colchicine-Induced Hepatotoxicity |journal=Toxins |language=en |volume=16 |issue=1 |pages=35 |doi=10.3390/toxins16010035 |doi-access=free |pmid=38251251 |pmc=10818746 |issn=2072-6651 }}</ref> As colchicine inhibits ] by preventing ] formation, it leads to multi-organ dysfunction. The early phase (10-24 hours post-ingestion) is characterized by gastrointestinal distress and initial ]. In the subsequent phase (2 to 7 days), patients may experience severe complications including ], ] (DIC), and cardiac issues due to direct toxicity on cardiac ].<ref name=":5">{{Cite web |title=Colchicine toxicity: What pharmacists need to know {{!}} BC Pharmacy Association |url=https://www.bcpharmacy.ca/news/colchicine-toxicity-what-pharmacists-need-know |access-date=2024-12-20 |website=www.bcpharmacy.ca}}</ref><ref name=":6">{{Cite journal |date=17 April 2020 |title=Clinical Manifestations and Outcomes of Colchicine Poisoning Cases; a Cross Sectional Study |pmc=7212071 |last1=Rahimi |first1=M. |last2=Alizadeh |first2=R. |last3=Hassanian-Moghaddam |first3=H. |last4=Zamani |first4=N. |last5=Kargar |first5=A. |last6=Shadnia |first6=S. |journal=Archives of Academic Emergency Medicine |volume=8 |issue=1 |pages=e53 |pmid=32440664 }}</ref><ref name=":7">{{Cite web |title=Orphanet: Colchicine poisoning |url=https://www.orpha.net/en/disease/detail/31824 |access-date=2024-12-20 |website=www.orpha.net}}</ref> The high affinity of colchicine for tissues like the liver and kidneys contributes to its rapid accumulation in these organs, leading to further complications.<ref name=":0" /><ref name=":1" />


== Symptoms ==
Symptoms typically manifest in three phases:


=== Phase 1 (10-24 hours) ===
This initial phase is characterized primarily by gastrointestinal symptoms, which can be severe and debilitating.<ref name=":2">{{Cite journal |date=16 November 2023 |title=Colchicine Poisoning: A Rare Case |pmc=10725528 |last1=Amaral |first1=A. |last2=Ferreira Da Silva |first2=D. |last3=Sampaio |first3=M. B. |last4=Salvado |first4=C. |journal=Cureus |volume=15 |issue=11 |pages=e48933 |doi=10.7759/cureus.48933 |doi-access=free |pmid=38106754 }}</ref><ref name=":3">{{Cite journal |last1=Fu |first1=Mingjie |last2=Zhao |first2=Jie |last3=Li |first3=Zhitao |last4=Zhao |first4=He |last5=Lu |first5=Anwei |date=2019 |title=Clinical outcomes after colchicine overdose: A case report |url=https://journals.lww.com/md-journal/fulltext/2019/07260/clinical_outcomes_after_colchicine_overdose__a.67.aspx |journal=Medicine |language=en-US |volume=98 |issue=30 |pages=e16580 |doi=10.1097/MD.0000000000016580|pmid=31348292 |pmc=6708822 }}</ref><ref name=":4">{{Cite web |title=Trend of Colchicine exposures reported to the Poisons Information Centre Erfurt |url=https://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Pharmakovigilanz/Risikoinformationen/RisikoBewVerf/a-f/colchicin_Posterpraesentation.pdf?__blob=publicationFile |access-date=20 December 2024 |website=Bfarm}}</ref> The most common early symptoms include nausea, vomiting, and abdominal pain, often intense and persistent. Diarrhea is another hallmark symptom, potentially becoming profuse and even ] in severe cases.<ref name=":4" /><ref name=":2" /> These symptoms can lead to significant ] due to excessive fluid loss.<ref name=":3" /> Patients may develop peripheral leukocytosis, an early increase in ] count.<ref name=":2" /><ref name=":3" /> This is often accompanied by electrolyte imbalances, including ], ], and ].<ref>{{Cite journal |date=16 December 2021 |title=Chronic colchicine poisoning with neuromyopathy, gastric ulcers and myelosuppression in a gout patient: A case report |pmc=8678875 |last1=Li |first1=M. M. |last2=Teng |first2=J. |last3=Wang |first3=Y. |journal=World Journal of Clinical Cases |volume=9 |issue=35 |pages=11050–11055 |doi=10.12998/wjcc.v9.i35.11050 |doi-access=free |pmid=35047617 }}</ref><ref name=":8">{{Cite journal |last1=Kisaarslan |first1=Ayşenur P. |last2=Yel |first2=Sibel |last3=Yilmaz |first3=Kenan |last4=Akyildiz |first4=Başak Nur |last5=Düşünsel |first5=Ruhan |last6=Gündüz |first6=Zübeyde |last7=Poyrazoğlu |first7=Hakan |last8=Yücel |first8=Gül |last9=Güven |first9=Feride |date=2015 |title=Colchicine Intoxication in Children: Four Case Reports |url=https://archivesofrheumatology.org/full-text/645 |journal=Archives of Rheumatology |volume=30 |issue=1 |pages=067–070 |doi=10.5606/ArchRheumatol.2015.4827 |issn=2148-5046}}</ref> The severe fluid loss and electrolyte disturbances can result in ]. Cardiovascular symptoms may also manifest during this phase. ] can occur as a result of the severe vomiting and diarrhea, often accompanied by ] as a compensatory mechanism. Some patients may develop a fever.


In more severe cases of colchicine poisoning, additional symptoms may appear during this initial phase. These can include ] (yellowing of the whites of the eyes), ] (decreased urine output), and ] (bluish discoloration of extremities).<ref name=":3" /> Some may experience ].<ref name=":3" /> It's crucial to note that even if symptoms appear mild during this initial phase, patients should be closely monitored. The onset of severe ] can be delayed, and the progression to subsequent phases can occur rapidly.<ref name=":2" /><ref name=":8" /> Therefore, any suspected case of colchicine poisoning should be treated as a medical emergency, regardless of the initial presentation's severity.


=== Phase 2 (2-7 days) ===
Phase 2 of colchicine poisoning is characterized by multi-organ dysfunction and potentially life-threatening complications. This phase is associated with a high mortality risk due to the potential for multi-organ failure and severe systemic effects.


One of the primary features of this phase is ], which can lead to ], including ], ], and ]. This hematopoietic inhibition increases the risk of severe ], which can develop into ], and bleeding tendencies.<ref name=":3" /><ref name=":9">{{Cite web |title=Colchicine: the good, the bad, the ugly and how to minimize the risks |url=https://academic.oup.com/rheumatology/article/63/4/936/7455266?login=false |access-date=20 December 2024 |website=Oxford Academic}}</ref> Cardiovascular complications are common during this phase. Patients may experience ], hypotension, and in severe cases, ] or ].<ref name=":3" /> Respiratory complications can also occur, with some patients developing ] (ARDS) that may necessitate ].<ref name=":10">{{Cite journal |last1=Schaffer |first1=D. H. |last2=Overbeek |first2=D. L. |last3=Erickson |first3=T. B. |last4=Boyer |first4=E. W. |last5=Goldfine |first5=C. |last6=Muhsin |first6=S. A. |last7=Chai |first7=P. R. |date=31 December 2022 |title=Severe colchicine poisoning treated successfully with kidney replacement therapy and plasmapheresis: a case report |journal=Taylor & Francis Online |volume=6 |issue=1 |pages=46–50 |doi=10.1080/24734306.2022.2055817 |pmc=9049641 |pmid=35497377}}</ref> Renal dysfunction is another hallmark of this phase, with oliguric renal failure being a common occurrence. This often requires renal replacement therapy, such as ] (CKRT).<ref name=":3" /><ref name=":10" /> Hepatic dysfunction may also develop, contributing to ] and metabolic disturbances.<ref name=":3" /> Neurological effects can manifest as changes in mental status, ranging from confusion to ].<ref name=":3" /> Some patients may develop disseminated intravascular coagulation (DIC), further complicating management.<ref name=":9" /> ], the breakdown of muscle tissue, can occur during this phase, exacerbating renal failure.<ref name=":3" /> The combination of these multi-system effects often results in a clinical picture of multiple organ failure, which may include hepatic, renal, respiratory, and circulatory failure.<ref name=":3" /><ref name=":10" />


=== Phase 3 (beyond 7 days) ===
Phase 3 typically occurs beyond 7 days after ingestion and is characterized by recovery and some distinctive symptoms.

A significant increase in white blood cell count occurs during this phase, contrasting with the bone marrow suppression seen in earlier stages.<ref name=":3" /><ref>{{Cite journal |date=2 January 2004 |title=Case report: fatal poisoning with Colchicum autumnale |pmc=420069 |last1=Brvar |first1=M. |last2=Ploj |first2=T. |last3=Kozelj |first3=G. |last4=Mozina |first4=M. |last5=Noc |first5=M. |last6=Bunc |first6=M. |journal=Critical Care (London, England) |volume=8 |issue=1 |pages=R56–R59 |doi=10.1186/cc2427 |doi-access=free |pmid=14975056 }}</ref> ] is a common feature of this phase, often temporary but sometimes extensive.<ref name=":3" /><ref name=":5" /> While improvement begins, full recovery can take several weeks.<ref>{{Cite web |title=Colchicine Toxicity |url=https://mobile.fpnotebook.com/Rheum/Pharm/ClchcnTxcty.htm |access-date=2024-12-20 |website=mobile.fpnotebook.com}}</ref>

It's important to note that not all patients experience all three phases distinctly. Some may have overlapping symptoms or skip certain phases entirely. Additionally, long-term effects may persist even after the acute poisoning has resolved. The occurrence and severity of Phase 3 symptoms largely depend on the initial dose ingested, the timeliness of treatment, and individual patient factors.

== Diagnosis ==
Diagnosis of colchicine poisoning is primarily clinical and relies on a combination of patient history, presenting symptoms, laboratory findings, and sometimes electrocardiographic (ECG) changes. A thorough history is crucial; it includes details about the timing of ingestion, amount consumed, and any co-ingestants.<ref name=":6" /><ref name=":7" /> Patients often present with gastrointestinal symptoms shortly after ingestion. Blood tests show an increase in white blood cell count, as well as possible hypokalemia or hypocalcemia.<ref name=":6" /><ref name=":11">{{Cite journal |date=19 May 2022 |title=Clinical, Laboratory, and Electrocardiographic Findings in Colchicine Toxicity: 10 Years of Experience |pmc=9160711 |last1=Sheibani |first1=M. |last2=Zamani |first2=N. |last3=Gerami |first3=A. H. |last4=Akhondi |first4=H. |last5=Hassanian-Moghaddam |first5=H. |journal=Frontiers in Medicine |volume=9 |doi=10.3389/fmed.2022.872528 |doi-access=free |pmid=35665351 }}</ref><ref name=":12">{{Cite journal |last1=Barbaria |first1=Wiem |last2=Khamassi |first2=Ichrak |last3=Fkili |first3=Mohamed |date=2023-12-31 |title=Pediatric colchicine poisoning with survival after a "lethal" overdose: a case report |url=https://www.tandfonline.com/doi/full/10.1080/24734306.2023.2236916 |journal=Taylor & Francis Online |volume=7 |doi=10.1080/24734306.2023.2236916}}</ref> Elevated liver enzymes (] and ]) indicate hepatic involvement.<ref name=":6" /> Prolonged ] (PT) and activated ] (PTT) are significant indicators of ] associated with severe poisoning.<ref name=":11" /> ECG monitoring is critical due to potential cardiac toxicity. Common abnormalities include ] changes (elevation or depression), ], and ].<ref name=":11" /><ref name=":12" /> While not routinely employed for diagnosis, imaging may be utilized to assess for complications such as ] or abdominal pathology if indicated by clinical presentation.<ref name=":3" />

== Treatment ==
The treatment of colchicine poisoning is primarily supportive since there is no specific antidote available. If colchicine ingestion has occurred within a few hours, ] should be administered promptly. Multiple-dose activated charcoal (MDAC) may be beneficial since colchicine undergoes ]; this helps interrupt the cycle and enhances elimination.<ref name=":13">{{Cite journal |date=7 October 2022 |title=Colchicine poisoning treated with hemoperfusion and hemodialysis: A case report |pmc=9540575 |last1=Ramezani |first1=M. |last2=Mostafazadeh |first2=B. |last3=Rahimi |first3=M. |last4=Evini |first4=P. E. |last5=Shadnia |first5=S. |journal=Clinical Case Reports |volume=10 |issue=10 |pages=e6419 |doi=10.1002/ccr3.6419 |pmid=36245450 }}</ref><ref>{{Cite web |title=Colchicine – extremely toxic in overdose |url=https://bpac.org.nz/BPJ/2014/september/docs/BPJ63-safer-prescribing.pdf |access-date=20 December 2024 |website=bpac NZ}}</ref> However, it must be noted that this approach is less effective in patients who are vomiting or have significant gastrointestinal distress.<ref name=":14">{{Cite web |last=Long |first=Neil |date=2019-03-05 |title=Colchicine toxicity |url=https://litfl.com/colchicine-toxicity/ |access-date=2024-12-20 |website=Life in the Fast Lane • LITFL |language=en-US}}</ref> Patients often present with ] due to fluid losses from vomiting and diarrhea. Large volumes of ] are required for rehydration.<ref name=":14" /> Electrolyte imbalances such as hypokalemia should be corrected promptly through supplementation. Continuous monitoring of electrolyte levels is essential during treatment.<ref name=":10" /> Patients exhibiting signs of multi-organ failure require intensive monitoring and supportive care measures. This may include ] for hypotension, renal replacement therapy if renal failure occurs, and management of any infectious complications that arise during hospitalization.<ref name=":13" /><ref name=":14" /> Although ] and ] are generally considered ineffective due to colchicine's large volume distribution, they have been used in severe cases where patients do not respond adequately to other treatments.<ref name=":13" /><ref name=":15">{{Cite journal |last1=Pérez Marín |first1=Maria |last2=Prod'hom |first2=Sylvain |last3=de Villiers |first3=Suzanne Francesca |last4=Ferry |first4=Thomas |last5=Amiet |first5=Vivianne |last6=Natterer |first6=Julia |last7=Perez |first7=Maria-Helena |last8=Buclin |first8=Thierry |last9=Chtioui |first9=Haithem |last10=Longchamp |first10=David |date=2021-04-07 |title=Case Report: Colchicine Toxicokinetic Analysis in a Poisoned Child Requiring Extracorporeal Life Support |journal=Frontiers in Pediatrics |language=English |volume=9 |doi=10.3389/fped.2021.658347 |doi-access=free |pmid=33898365 |pmc=8058177 |issn=2296-2360}}</ref> In some instances, ] has been explored but remains controversial.<ref name=":15" /><ref name=":16">{{Cite journal |date=26 August 2022 |title=Progress in the management of acute colchicine poisoning in adults |pmc=9417090 |last1=Wu |first1=J. |last2=Liu |first2=Z. |journal=Internal and Emergency Medicine |volume=17 |issue=7 |pages=2069–2081 |doi=10.1007/s11739-022-03079-6 |pmid=36028733 }}</ref> In extreme cases involving severe cardiogenic shock or multi-organ failure unresponsive to conventional therapies, ] has been utilized successfully.<ref name=":15" /> This approach provides temporary support while allowing time for recovery from toxic effects.

== Risks ==
Many cases of colchicine poisoning occur unintentionally. Children are particularly at risk; studies indicate that approximately 43% of reported cases involve toddlers who gain unsupervised access to colchicine tablets.<ref name=":17">{{Cite web |title=Colchicine: extremely toxic in overdose |url=https://www.gov.uk/drug-safety-update/colchicine-extremely-toxic-in-overdose |access-date=2024-12-20 |website=GOV.UK |language=en}}</ref><ref name=":18">{{Cite web |title=Colchicine: painful insights from recent poisoning data in New Zealand |url=https://www.medsafe.govt.nz/profs/PUArticles/June2021/Colchicine-painful-insights-recent-poisoning-data-New-Zealand.html |access-date=2024-12-20 |website=www.medsafe.govt.nz |language=en-nz}}</ref> Due to their small size, even one or two tablets can lead to severe toxicity. A substantial proportion of poisonings arise from dosing errors among adults who misunderstand how to take colchicine properly or exceed recommended doses in attempts to manage ] symptoms effectively.<ref name=":17" /><ref name=":18" /> Certain groups are at higher risk for severe toxicity including individuals with pre-existing renal or hepatic impairment, those with gastrointestinal or ], and patients at extremes of age—particularly elderly individuals who may have multiple ].<ref name=":5" /><ref name=":17" /> Colchicine is sometimes used in suicide attempts or self-harm situations due to its high toxicity profile.<ref name=":17" /><ref name=":18" />

== Prognosis ==
The prognosis of colchicine poisoning varies significantly depending on the severity of the ] and the timeliness of treatment. Colchicine doses >0.5 mg/kg, and especially >0.8 mg/kg, are generally fatal.<ref name=":9" /> In a study of 43 patients over 10 years, the lowest lethal dose was 0.63 mg/kg.<ref>{{Cite journal |last=Mitev |first=Vanyo |date=2023-11-23 |title=What is the lowest lethal dose of colchicine? |url=https://www.tandfonline.com/doi/full/10.1080/13102818.2023.2288240 |journal=Taylor & Francis Online |volume=37 |doi=10.1080/13102818.2023.2288240 |issn=1310-2818}}</ref> The fatality rate of acute colchicine poisoning may range from 14.3% to 25.6%.<ref name=":16" /> Survivors can experience a prolonged recovery period, with some symptoms persisting for weeks or even months after the acute poisoning event.


== References == == References ==
<!-- Inline citations added to your article will automatically display here. See en.wikipedia.org/WP:REFB for instructions on how to add citations. --> <!-- Inline citations added to your article will automatically display here. See en.wikipedia.org/WP:REFB for instructions on how to add citations. -->
{{reflist}} {{reflist}}

== External Links ==
{{Medical resources
| ICD10 = T50.4
| ICD11 = NE60
| Orphanet = 31824
}}

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An article on Colchicine Poisoning and its effects on the body

Colchicine poisoning occurs due to the ingestion of colchicine, a drug derived from the plant colchicum autumnale, and can be life-threatening.

Pathophysiology

Colchicine's toxicity arises primarily from its mechanism of action, which involves binding to tubulin and disrupting microtubule formation, leading to impaired cellular processes. This disruption affects rapidly dividing cells, particularly in the gastrointestinal tract and bone marrow, resulting in significant gastrointestinal symptoms such as nausea, vomiting, and diarrhea due to rapid turnover of intestinal mucosal cells. The drug is metabolized in the liver, primarily by cytochrome P450 enzymes, leading to the formation of several metabolites, including 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC). These metabolites can exhibit increased toxicity compared to the parent compound, contributing to hepatic injury and other systemic effects. As colchicine inhibits mitosis by preventing spindle formation, it leads to multi-organ dysfunction. The early phase (10-24 hours post-ingestion) is characterized by gastrointestinal distress and initial leukocytosis. In the subsequent phase (2 to 7 days), patients may experience severe complications including renal failure, disseminated intravascular coagulation (DIC), and cardiac issues due to direct toxicity on cardiac myocytes. The high affinity of colchicine for tissues like the liver and kidneys contributes to its rapid accumulation in these organs, leading to further complications.

Symptoms

Symptoms typically manifest in three phases:

Phase 1 (10-24 hours)

This initial phase is characterized primarily by gastrointestinal symptoms, which can be severe and debilitating. The most common early symptoms include nausea, vomiting, and abdominal pain, often intense and persistent. Diarrhea is another hallmark symptom, potentially becoming profuse and even bloody in severe cases. These symptoms can lead to significant dehydration due to excessive fluid loss. Patients may develop peripheral leukocytosis, an early increase in white blood cell count. This is often accompanied by electrolyte imbalances, including hyponatremia, hypocalcemia, and hypokalemia. The severe fluid loss and electrolyte disturbances can result in metabolic acidosis. Cardiovascular symptoms may also manifest during this phase. Hypotension can occur as a result of the severe vomiting and diarrhea, often accompanied by tachycardia as a compensatory mechanism. Some patients may develop a fever.

In more severe cases of colchicine poisoning, additional symptoms may appear during this initial phase. These can include scleral icterus (yellowing of the whites of the eyes), oliguria (decreased urine output), and peripheral cyanosis (bluish discoloration of extremities). Some may experience hypothermia. It's crucial to note that even if symptoms appear mild during this initial phase, patients should be closely monitored. The onset of severe toxicity can be delayed, and the progression to subsequent phases can occur rapidly. Therefore, any suspected case of colchicine poisoning should be treated as a medical emergency, regardless of the initial presentation's severity.

Phase 2 (2-7 days)

Phase 2 of colchicine poisoning is characterized by multi-organ dysfunction and potentially life-threatening complications. This phase is associated with a high mortality risk due to the potential for multi-organ failure and severe systemic effects.

One of the primary features of this phase is bone marrow suppression, which can lead to pancytopenia, including neutropenia, thrombocytopenia, and anemia. This hematopoietic inhibition increases the risk of severe infections, which can develop into sepsis, and bleeding tendencies. Cardiovascular complications are common during this phase. Patients may experience cardiac arrhythmias, hypotension, and in severe cases, cardiogenic shock or cardiac arrest. Respiratory complications can also occur, with some patients developing acute respiratory distress syndrome (ARDS) that may necessitate mechanical ventilation. Renal dysfunction is another hallmark of this phase, with oliguric renal failure being a common occurrence. This often requires renal replacement therapy, such as continuous kidney replacement therapy (CKRT). Hepatic dysfunction may also develop, contributing to coagulopathy and metabolic disturbances. Neurological effects can manifest as changes in mental status, ranging from confusion to coma. Some patients may develop disseminated intravascular coagulation (DIC), further complicating management. Rhabdomyolysis, the breakdown of muscle tissue, can occur during this phase, exacerbating renal failure. The combination of these multi-system effects often results in a clinical picture of multiple organ failure, which may include hepatic, renal, respiratory, and circulatory failure.

Phase 3 (beyond 7 days)

Phase 3 typically occurs beyond 7 days after ingestion and is characterized by recovery and some distinctive symptoms.

A significant increase in white blood cell count occurs during this phase, contrasting with the bone marrow suppression seen in earlier stages. Alopecia is a common feature of this phase, often temporary but sometimes extensive. While improvement begins, full recovery can take several weeks.

It's important to note that not all patients experience all three phases distinctly. Some may have overlapping symptoms or skip certain phases entirely. Additionally, long-term effects may persist even after the acute poisoning has resolved. The occurrence and severity of Phase 3 symptoms largely depend on the initial dose ingested, the timeliness of treatment, and individual patient factors.

Diagnosis

Diagnosis of colchicine poisoning is primarily clinical and relies on a combination of patient history, presenting symptoms, laboratory findings, and sometimes electrocardiographic (ECG) changes. A thorough history is crucial; it includes details about the timing of ingestion, amount consumed, and any co-ingestants. Patients often present with gastrointestinal symptoms shortly after ingestion. Blood tests show an increase in white blood cell count, as well as possible hypokalemia or hypocalcemia. Elevated liver enzymes (AST and ALP) indicate hepatic involvement. Prolonged prothrombin time (PT) and activated partial thromboplastin time (PTT) are significant indicators of coagulopathy associated with severe poisoning. ECG monitoring is critical due to potential cardiac toxicity. Common abnormalities include ST segment changes (elevation or depression), sinus tachycardia, and left atrial enlargement. While not routinely employed for diagnosis, imaging may be utilized to assess for complications such as pulmonary edema or abdominal pathology if indicated by clinical presentation.

Treatment

The treatment of colchicine poisoning is primarily supportive since there is no specific antidote available. If colchicine ingestion has occurred within a few hours, activated charcoal should be administered promptly. Multiple-dose activated charcoal (MDAC) may be beneficial since colchicine undergoes Enterohepatic recirculation; this helps interrupt the cycle and enhances elimination. However, it must be noted that this approach is less effective in patients who are vomiting or have significant gastrointestinal distress. Patients often present with hypovolemia due to fluid losses from vomiting and diarrhea. Large volumes of intravenous fluids are required for rehydration. Electrolyte imbalances such as hypokalemia should be corrected promptly through supplementation. Continuous monitoring of electrolyte levels is essential during treatment. Patients exhibiting signs of multi-organ failure require intensive monitoring and supportive care measures. This may include vasopressors for hypotension, renal replacement therapy if renal failure occurs, and management of any infectious complications that arise during hospitalization. Although hemodialysis and hemoperfusion are generally considered ineffective due to colchicine's large volume distribution, they have been used in severe cases where patients do not respond adequately to other treatments. In some instances, plasma exchange has been explored but remains controversial. In extreme cases involving severe cardiogenic shock or multi-organ failure unresponsive to conventional therapies, extracorporeal life support has been utilized successfully. This approach provides temporary support while allowing time for recovery from toxic effects.

Risks

Many cases of colchicine poisoning occur unintentionally. Children are particularly at risk; studies indicate that approximately 43% of reported cases involve toddlers who gain unsupervised access to colchicine tablets. Due to their small size, even one or two tablets can lead to severe toxicity. A substantial proportion of poisonings arise from dosing errors among adults who misunderstand how to take colchicine properly or exceed recommended doses in attempts to manage gout symptoms effectively. Certain groups are at higher risk for severe toxicity including individuals with pre-existing renal or hepatic impairment, those with gastrointestinal or cardiac diseases, and patients at extremes of age—particularly elderly individuals who may have multiple comorbidities. Colchicine is sometimes used in suicide attempts or self-harm situations due to its high toxicity profile.

Prognosis

The prognosis of colchicine poisoning varies significantly depending on the severity of the overdose and the timeliness of treatment. Colchicine doses >0.5 mg/kg, and especially >0.8 mg/kg, are generally fatal. In a study of 43 patients over 10 years, the lowest lethal dose was 0.63 mg/kg. The fatality rate of acute colchicine poisoning may range from 14.3% to 25.6%. Survivors can experience a prolonged recovery period, with some symptoms persisting for weeks or even months after the acute poisoning event.

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