Colchicine Poisoning

Complex MONDO:0017859 Pathograph 16 Show in embeddings browser Poisoning

Colchicine poisoning follows exposure to a drug with a narrow therapeutic index and no clear boundary between a therapeutic, a toxic and a lethal dose. It arrives by three routes: acute overdose of the drug taken in self-harm or in error, slow accumulation at ordinary prescribed doses when renal or hepatic clearance falls or a CYP3A4 or P-glycoprotein inhibitor is co-prescribed, and ingestion of a colchicine-containing plant. All three converge on one molecular lesion. Colchicine binds tubulin and prevents microtubule assembly, and every downstream injury is an extension of that binding. The cells that depend most on the mitotic spindle fail first, so the gut mucosa and then the bone marrow give way, and it is the resulting pancytopenia with neutropenic sepsis that kills. The cells that depend on microtubule-based transport rather than on mitosis fail far more slowly, producing the proximal myopathy and accompanying peripheral neuropathy that characterise the chronic-accumulation route. One lesion, two tissues, two clocks. There is no antidote in routine clinical use.

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12
Pathophys.
1
Histopath.
15
Phenotypes
16
Pathograph
4
Medical Actions
1
Deep Research
⚙

Pathophysiology

12
Colchicine Exposure Exceeding the Therapeutic Window
Systemic colchicine burden above what the patient can tolerate, reached by a single large ingestion of tablets or plant material, or by accumulation at ordinary doses. The drug has no clear-cut boundary between nontoxic, toxic and lethal doses, which is why the routes are not usefully separated at the level of the exposure - the determinant is the concentration reached, not the size of any one dose.
Downstream
Colchicine-Tubulin Binding and Microtubule Assembly Failure The systemic burden is what delivers colchicine to intracellular tubulin. Colchicine distributes very widely and binds intracellular elements, so the tissue concentration follows the systemic one closely.
Show evidence (3 references)
PMID:20586571 SUPPORT Other
"It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians."
States the narrow index and the absence of a dose boundary, which is the claim this node rests on.
PMID:20586571 SUPPORT Other
"High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg."
Gives the acute-ingestion thresholds reported in the systematic review.
PMID:30888889 SUPPORT Human Clinical
"Admission colchicine concentrations were highly correlated with a fatal outcome [median 7.8 ng/ml (IQR: 5.8-18.7) vs 1.2 (0-2.3) in survivors]."
Ties measured concentration rather than ingested dose to outcome in a 297-patient cohort, which is the basis for this node being defined by concentration reached.
Impaired Colchicine Clearance via CYP3A4 and P-Glycoprotein Inhibition
Colchicine is metabolised by CYP3A4 and effluxed by P-glycoprotein, so a drug that inhibits either raises the concentration reached at an unchanged prescribed dose. Renal or hepatic impairment does the same thing by a different route. This is the mechanism behind the toxicity that appears at ordinary doses, and it is the reason a patient can be poisoned without ever taking an overdose.
P-glycoprotein-mediated colchicine efflux GO:0042908 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased P-glycoprotein-mediated colchicine efflux, annotated with xenobiotic transport (GO:0042908). GO:0042908 is a biological process from the Gene Ontology. ↓ DECREASED
CYP3A4-mediated colchicine oxidation GO:0004497 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased CYP3A4-mediated colchicine oxidation, annotated with monooxygenase activity (GO:0004497). GO:0004497 is a molecular function from the Gene Ontology. ↓ DECREASED
Downstream
Colchicine Exposure Exceeding the Therapeutic Window Reduced clearance raises the concentration reached at an unchanged dose, so the interaction produces the exposure node rather than acting beside it.
Show evidence (5 references)
PMID:36028733 SUPPORT Other
"Colchicine is metabolized to 2- and 3-demethylcolchicine by the CYP 3A4 isoform of cytochrome P450 in hepatocytes, followed by biliary excretion"
Establishes CYP3A4 as the metabolic route whose inhibition raises exposure.
PMID:20586571 SUPPORT Other
"CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations."
Names the interacting inhibitors and states that they raise colchicine concentrations.
PMID:36028733 SUPPORT Other
"In addition to CYP3A4, P-glycoprotein that is an ATPase efflux pump can extrude colchicine from the enterocytes to prevent gastrointestinal absorption"
Establishes the P-glycoprotein efflux arm this node names alongside CYP3A4, and locates it at the enterocyte, limiting absorption.
+ 2 more references
Colchicine-Tubulin Binding and Microtubule Assembly Failure
Colchicine binds tubulin dimers in roughly equimolar fashion and prevents them polymerising into microtubules. This is the same binding that makes the drug therapeutic at low dose, and the entire toxicity is a continuation of it - not a separate off-target effect. Microtubules serve both the mitotic spindle and intracellular transport, which is why one lesion produces two clinically distinct syndromes.
microtubule polymerization GO:0046785 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased microtubule polymerization (GO:0046785). GO:0046785 is a biological process from the Gene Ontology. ↓ DECREASED
tubulin binding GO:0015631 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves tubulin binding (GO:0015631). GO:0015631 is a molecular function from the Gene Ontology.
Downstream
Mitotic Arrest in Rapidly Proliferating Tissue Without assembling microtubules there is no mitotic spindle, so cells attempting division arrest. Tissues with the highest proliferative fraction therefore declare first.
Cardiac Myocyte Conduction and Contractility Failure The same microtubule collapse interrupts conduction and contractility in cardiac myocytes. This arm depends on neither mitosis nor axonal length, so it runs on the fast clock alongside the gut and marrow rather than with the neuromyopathy.
Microtubule-Dependent Intracellular Transport Failure The same assembly block removes the tracks for microtubule-based transport. This arm is independent of cell division, which is why it can affect post-mitotic muscle and nerve.
Show evidence (3 references)
PMID:20586571 SUPPORT Other
"Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network."
States both the binding target and that the toxicity is continuous with the therapeutic mechanism, which is the framing of this node.
PMID:20661070 SUPPORT Human Clinical
"Colchicine, a long established anti-inflammatory agent now used in several rheumatologic conditions, acts by inhibiting microtubular polymerization, as it binds equimolarly to tubulin molecules."
Gives the stoichiometry and the polymerisation block underlying this node.
PMID:34229452 SUPPORT Human Clinical
"The primary mechanism of action is binding to tubulins blocking the production and lengthening of microtubules, which make up the skeleton of cells."
Independent statement of the same binding and assembly block.
Mitotic Arrest in Rapidly Proliferating Tissue
Cells attempting division without a spindle arrest and die. The tissues with the highest proliferative fraction - gut mucosa, bone marrow, hair follicle - are therefore the ones that declare first, and in that order clinically.
mitotic cell cycle GO:0000278 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased mitotic cell cycle (GO:0000278). GO:0000278 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Gastrointestinal Mucosal Injury The intestinal epithelium turns over faster than any other tissue here, so it fails earliest - within the first day, before the marrow.
Hepatic and Renal Injury The review attributes the hepatic and renal dysfunction to the same inhibition of mitosis, which is why this injury is placed downstream of the arrest node rather than treated as a separate toxic mechanism.
Bone Marrow Hematopoietic Suppression Haematopoietic progenitors arrest, and the marrow's output falls. The delay before this becomes visible in the blood is the transit time of the circulating cells already made, not a delay in the injury itself.
Show evidence (1 reference)
PMID:36028733 SUPPORT Other
"the organs with active cell proliferation, such as the gastrointestinal tract, bone marrow, and hair follicles, are often the most susceptible to the toxic effects of colchicine"
Names the proliferative tissues that this node predicts will be affected first, and states the reason as their proliferation.
Gastrointestinal Mucosal Injury
Injury to the rapidly renewing intestinal epithelium, producing the vomiting, abdominal pain and profuse diarrhoea that open the illness. Clinically this is the phase that looks like gastroenteritis, and it is where the poisoning is most often missed.
Downstream
Neutropenic Sepsis and Progressive Multi-Organ Failure Fluid and electrolyte loss from the mucosal injury produces hypovolaemia and shock, which is one of the components of the terminal multi-organ picture. The intermediates are volume depletion and hypoperfusion.
Show evidence (1 reference)
PMID:36028733 SUPPORT Other
"Acute colchicine poisoning can lead to original gastrointestinal disorders, shock, progressive multiple organ failure, and myelosuppression."
Places the gastrointestinal disturbance first in the sequence this node occupies.
Bone Marrow Hematopoietic Suppression
Failure of marrow output across all three lineages once dividing progenitors are arrested. This is the step that makes colchicine poisoning lethal rather than merely severe, and it is why the second phase of the illness is the dangerous one even when the patient looks better than they did on day one.
Downstream
Multilineage Peripheral Cytopenias Marrow failure shows in the blood as the existing circulating cells are consumed and not replaced, so the cytopenia lags the marrow injury by roughly the lifespan of each lineage.
Show evidence (1 reference)
PMID:36028733 SUPPORT Other
"Acute colchicine poisoning can lead to original gastrointestinal disorders, shock, progressive multiple organ failure, and myelosuppression."
Names myelosuppression as a consequence of acute colchicine poisoning.
Multilineage Peripheral Cytopenias
Pancytopenia, with neutropenia the component that matters. Anaemia and thrombocytopenia follow on their own slower timescales, and the coagulopathy seen in severe cases is not purely a platelet problem - disseminated intravascular coagulation is reported alongside it.
Downstream
Neutropenic Sepsis and Progressive Multi-Organ Failure Loss of neutrophils removes the defence against infection in a patient whose gut mucosal barrier is already injured, so the two arms of the poisoning compound each other. Positive blood cultures were recorded in 5 of 20 patients in the cited series; the route of entry was not established there, so no claim of bacterial translocation is made.
Show evidence (1 reference)
PMID:34229452 SUPPORT Human Clinical
"He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis."
Documents pancytopenia with absolute neutropenia, and the disseminated intravascular coagulation this node's description separates from thrombocytopenia.
Neutropenic Sepsis and Progressive Multi-Organ Failure
The terminal phase: sepsis in a patient with no neutrophils, on a background of shock, acute kidney injury, hepatic failure, rhabdomyolysis and lactic acidosis. Reported case-fatality in acute poisoning runs to a quarter of patients.
Show evidence (2 references)
PMID:36028733 SUPPORT Other
"the fatality rate of acute colchicine poisoning may range from 14.3 to 25.6%"
Gives the reported case-fatality range this node states.
PMID:20586571 SUPPORT Other
"The culmination of these mechanisms leads to multi-organ dysfunction and failure."
States multi-organ failure as the endpoint of the mechanisms above.
Microtubule-Dependent Intracellular Transport Failure
Loss of the microtubule tracks on which intracellular cargo moves. In muscle and in long peripheral axons this matters more than mitosis does, because those cells are post-mitotic and depend on transport over distances no other mechanism can cover. This arm is slower than the marrow arm and is what dominates the chronic-accumulation route.
microtubule-based transport GO:0099111 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased microtubule-based transport (GO:0099111). GO:0099111 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Colchicine Neuromyopathy Transport failure in myocytes and in peripheral axons produces the vacuolar myopathy and the accompanying axonal neuropathy. The intermediates - lysosomal accumulation in the vacuolar myopathy, distal axonal degeneration in the neuropathy - are described in the clinical literature, so the link is not direct.
Show evidence (1 reference)
PMID:20661070 SUPPORT Human Clinical
"Cytoskeletal microtubules are crucial in processes of cell viability, such as mitosis and intracellular vesicle motility."
Names intracellular vesicle motility alongside mitosis as a microtubule function, which is the division this node depends on. The statement is about microtubule function generally rather than about axons specifically.
Colchicine Neuromyopathy
Proximal myopathy with elevated creatine kinase, accompanied in about half of reported cases by a peripheral neuropathy. It is characteristically insidious, arises at ordinary therapeutic doses rather than in overdose, and resolves on stopping the drug - which is what separates it from the acute poisoning syndrome and makes recognising it worthwhile.
Show evidence (3 references)
PMID:36512928 SUPPORT Human Clinical
"A total of 143 cases of neuromyopathy from 99 articles were identified as having a "definite" or "probable" association with colchicine usage"
Establishes the entity and its size in the published literature by systematic review.
PMID:36512928 SUPPORT Human Clinical
"Most of these cases presented with features of both neuropathy and myopathy"
Supports the combined neuropathy-and-myopathy presentation this node describes. It establishes co-occurrence only; it does not characterise the fibre pathology as axonal, and the node notes record that limit.
PMID:19078054 SUPPORT Other
"Colchicine myopathy can complicate standard treatment of gout, especially in those patients with underlying renal insufficiency."
States that the myopathy arises during standard treatment and is potentiated by renal impairment, which is the chronic-accumulation route.
Hepatic and Renal Injury
Injury to the two organs that clear colchicine. This node matters less for the organ failure it names than for what it does to the rest of the pathograph: hepatic elimination carries most of the drug's clearance, so damaging the liver slows removal of the poison doing the damage. The loop is why late presentation and pre-existing hepatic or renal impairment carry a worse prognosis.
hepatocyte CL:0000182 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves hepatocyte (CL:0000182). CL:0000182 is a cell type from the Cell Ontology.
Downstream
Colchicine Exposure Exceeding the Therapeutic Window Injury to the clearing organs slows elimination and so raises the systemic burden, closing a positive feedback loop back onto the head of the pathograph. The intermediate is reduced hepatic metabolism and biliary excretion.
Show evidence (2 references)
PMID:36028733 SUPPORT Other
"Colchicine and its metabolites are mainly eliminated through the liver. The kidneys contribute only 10–20% of the total colchicine clearance"
Establishes that clearance is predominantly hepatic, which is what makes liver injury a rate-limiting step for elimination rather than only an organ failure.
PMID:20586571 SUPPORT Other
"Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis."
Links pre-existing hepatic and renal impairment to worse outcome, which is the prognostic consequence of this node.
Cardiac Myocyte Conduction and Contractility Failure
Interruption of conduction and contractility in cardiac muscle, giving arrhythmia and depressed contractility. This is the organ dysfunction most frequently recorded in the published adult case series, and it is not a proliferation effect - cardiac myocytes are post-mitotic, so this arm shows that the poisoning is not only a spindle poison.
cardiac myocyte CL:0000746 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves cardiac myocyte, annotated with cardiac muscle cell (CL:0000746). CL:0000746 is a cell type from the Cell Ontology.
Downstream
Neutropenic Sepsis and Progressive Multi-Organ Failure Cardiac failure contributes to the shock state that defines the terminal phase, alongside the septic and hypovolaemic components.
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Organ dysfunction, n (%) Acute myocardial injury16 (80%) Acidosis14 (70%) Acute kidney injury15 (75%)"
Records acute myocardial injury in 16 of 20 patients, the most frequent organ dysfunction in that published series. The denominator is a series of published case reports and skews severe, so no frequency band is asserted.
✶

Histopathology

1
Vacuolar myopathy
Vacuolar change in muscle on biopsy, the characteristic finding sought when the diagnosis needs settling. The source says it is typically present, not invariably, so it is not curated as a required feature. It is the tissue-level correlate of the transport-failure arm rather than of the mitotic arm.
Show evidence (1 reference)
PMID:19078054 SUPPORT Other
"Definitive diagnosis usually requires histologic examination where a characteristic vacuolar myopathy is typically present."
States the characteristic histology and its role in definitive diagnosis.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Colchicine Poisoning Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

15
Blood 4
Pancytopenia HP:0001876 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pancytopenia (HP:0001876), qualified as temporality acute. HP:0001876 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:34229452 SUPPORT Human Clinical
"He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis."
Documents pancytopenia in a case of acute colchicine poisoning. No frequency band is asserted, because the published series available here over-represent severe poisoning.
Decreased total neutrophil count HP:0001875 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Neutropenia, annotated with Decreased total neutrophil count (HP:0001875), qualified as temporality acute. HP:0001875 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:34229452 SUPPORT Human Clinical
"He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis."
Documents absolute neutropenia in acute colchicine poisoning.
Thrombocytopenia HP:0001873 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Thrombocytopenia (HP:0001873), qualified as temporality acute. HP:0001873 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%) Thrombocytopenia12 (60%)"
Reports thrombocytopenia in 12 of 20 patients in the published series. No band is asserted from this denominator.
Anemia HP:0001903 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anemia (HP:0001903), qualified as temporality acute. HP:0001903 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Anemia8 (40%) Coagulation disorders15 (75%)"
Reports anaemia in 8 of 20 patients in the published series.
Cardiovascular 1
Hypotension HP:0002615 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotension (HP:0002615), qualified as temporality acute. HP:0002615 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia)."
Names hypotension as part of the characteristic toxidrome.
Digestive 3
Diarrhea FREQUENT HP:0002014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diarrhea (HP:0002014), qualified as temporality acute. HP:0002014 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1 (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)"
Reports diarrhoea in 14 of 20 patients. The denominator is a series of 20 published adult case reports, which skews towards severe poisoning; the FREQUENT band is taken as a conservative reading of that figure rather than as a population frequency.
Vomiting FREQUENT HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013), qualified as temporality acute. HP:0002013 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1 (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)"
Reports vomiting in 14 of 20 patients in the same published series, with the same denominator caveat.
Decreased liver function HP:0001410 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatic injury, annotated with Decreased liver function (HP:0001410), qualified as temporality acute. HP:0001410 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%) Thrombocytopenia12 (60%)"
Reports liver damage in 12 of 20 patients in the published series.
Genitourinary 1
Acute kidney injury HP:0001919 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acute kidney injury (HP:0001919), qualified as temporality acute. HP:0001919 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (2 references)
PMID:36028733 SUPPORT Human Clinical
"Organ dysfunction, n (%) Acute myocardial injury16 (80%) Acidosis14 (70%) Acute kidney injury15 (75%)"
Reports acute kidney injury in 15 of 20 patients in the published series.
PMID:30888889 SUPPORT Human Clinical
"Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and rhabdomyolysis."
Qualifies the severity of this phenotype by exposure route: it was mild in a 297-patient plant-ingestion cohort, against the severe injury reported in tablet overdose. The phenotype is route-dependent and the entry should not be read as asserting one severity.
Integument 1
Alopecia HP:0001596 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Alopecia (HP:0001596). HP:0001596 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36028733 SUPPORT Other
"the organs with active cell proliferation, such as the gastrointestinal tract, bone marrow, and hair follicles, are often the most susceptible to the toxic effects of colchicine"
Names the hair follicle as a susceptible proliferative tissue. This supports the mechanism; it is not a direct report of alopecia frequency, and no frequency band is asserted.
Metabolism 1
Lactic acidosis HP:0003128 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lactic acidosis (HP:0003128), qualified as temporality acute. HP:0003128 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia)."
Names lactic acidosis as part of the characteristic toxidrome.
Musculoskeletal 2
Rhabdomyolysis HP:0003201 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rhabdomyolysis (HP:0003201), qualified as temporality acute. HP:0003201 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (2 references)
PMID:36028733 SUPPORT Human Clinical
"Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%) Thrombocytopenia12 (60%)"
Reports rhabdomyolysis in 9 of 20 patients in the published series.
PMID:30888889 SUPPORT Human Clinical
"Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and rhabdomyolysis."
Qualifies the severity of this phenotype by exposure route: it was mild in a 297-patient plant-ingestion cohort, against the severe injury reported in tablet overdose. The phenotype is route-dependent and the entry should not be read as asserting one severity.
Proximal muscle weakness HP:0003701 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Proximal muscle weakness (HP:0003701), qualified as temporality chronic. HP:0003701 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:36512928 SUPPORT Human Clinical
"Cases generally present with proximal myopathy symptoms."
States proximal myopathy as the general presentation across 143 systematically reviewed cases.
Nervous System 1
Peripheral neuropathy HP:0009830 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Peripheral neuropathy (HP:0009830), qualified as temporality chronic. HP:0009830 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:36512928 SUPPORT Human Clinical
"Most of these cases presented with features of both neuropathy and myopathy"
Establishes that neuropathy co-occurs with myopathy in the majority of the 143 reviewed cases.
Constitutional 1
Abdominal pain FREQUENT HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027), qualified as temporality acute. HP:0002027 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:36028733 SUPPORT Human Clinical
"Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1 (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)"
Reports abdominal pain in 14 of 20 patients, same series and same caveat.
💊

Medical Actions

4
Granulocyte colony-stimulating factor
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: filgrastim NCIT:C1474 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses filgrastim (NCIT:C1474). NCIT:C1474 is a therapeutic agent from the NCI Thesaurus.
Platform: Other
G-CSF is given to shorten the neutropenic phase. It does not oppose the tubulin lesion and it cannot restart a progenitor that is arrested; it acts on the marrow's output once the drug is clearing, which is why it is described as supportive rather than as an antidote. It is the one pharmacological measure here that is aimed at a specific node of this pathograph.
Mechanism Target:
MODULATES Bone Marrow Hematopoietic Suppression — Stimulates granulopoiesis to shorten the period of neutropenia. Recorded as MODULATES rather than RESTORES because the cited reports describe recovery of counts under treatment, not a demonstrated reversal of the marrow lesion against a control.
Show evidence (1 reference)
PMID:1384817 SUPPORT Human Clinical
"His pancytopenia resolved after subcutaneous administration of one 300-micrograms dose of G-CSF."
Reports resolution of the cytopenia after G-CSF in a single case. A single uncontrolled case cannot separate the drug's effect from spontaneous marrow recovery, which is why the effect is graded MODULATES.
Show evidence (2 references)
PMID:20586571 SUPPORT Other
"Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment."
Establishes G-CSF within supportive care as the mainstay, which is the role this entry gives it.
PMID:7530779 SUPPORT Human Clinical
"The pancytopenia responded to granulocyte colony-stimulating factor 300 micrograms on days 4, 5, 6, and 8."
A second case reporting response of the pancytopenia to G-CSF, with the dosing schedule.
Activated charcoal
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Agent: activated charcoal CHEBI:91090 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses activated charcoal, annotated with charcoal (CHEBI:91090). CHEBI:91090 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Other
Gastrointestinal decontamination. Colchicine undergoes significant enterohepatic recirculation, which is a specific argument for charcoal here beyond the generic one, though the cited review recommends it on timing grounds without invoking that. The same recommendation reserves gastric lavage for very large ingestions presenting within an hour, so lavage is a narrow adjunct to charcoal rather than a separate treatment, and it is not curated as one.
Show evidence (2 references)
PMID:20586571 SUPPORT Other
"Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage."
States the decontamination recommendation and its timing constraint.
PMID:36028733 SUPPORT Other
"Colchicine and its metabolites undergo significant enterohepatic re-circulation which may further lead to its retention in the body"
Documents the enterohepatic recirculation this entry names as an additional argument for charcoal. The source states the recirculation, not that charcoal interrupts it.
Withdrawal of colchicine and of interacting drugs
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Platform: Other
For the chronic-accumulation neuromyopathy this is the treatment, and it works: symptoms resolved completely in 70 percent of reviewed cases at a median of 21 days. Rechallenge at a reduced dose was usually tolerated, which matters clinically for patients with familial Mediterranean fever who have few alternatives.
Mechanism Target:
INHIBITS Colchicine Exposure Exceeding the Therapeutic Window — Stopping the drug removes the exposure at the head of the pathograph, which is why the downstream neuromyopathy reverses.
Show evidence (1 reference)
PMID:36512928 SUPPORT Human Clinical
"Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days."
Demonstrates that removing the exposure reverses the downstream syndrome, which is the claim of this link.
Show evidence (1 reference)
PMID:19078054 SUPPORT Other
"It is important to be aware of this entity, as the discontinuation of colchicine will allow a prompt remission."
States discontinuation as the effective intervention for the myopathy.
Intensive supportive care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Platform: Other
Mechanical ventilation, vasopressors, renal replacement therapy, transfusion and antimicrobial cover for the neutropenic phase. In a poisoning with no antidote and a reversible lesion, keeping the patient alive through the cytopenic window is the whole of the treatment.
Show evidence (4 references)
PMID:36028733 SUPPORT Other
"there are currently no specific antidotes for colchicine poisoning"
Establishes the absence of an antidote, which is why supportive care carries the treatment.
PMID:7530779 SUPPORT Human Clinical
"Although anticolchicine monoclonal antibody administration is the only specific therapy described, intensive supportive care including granulocyte colony-stimulating factor administration can facilitate recovery from severe colchicine intoxication."
States that intensive supportive care can carry a patient through severe poisoning.
PMID:20586571 SUPPORT Other
"Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available."
Records that the one specific therapy described is unavailable in practice, which is why this entry curates supportive care rather than an antidote.
+ 1 more reference
🌍

Environmental Factors

2
Colchicine exposure above the therapeutic window
exposure to colchicine ECTO:0000509 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to colchicine, annotated with exposure to drug (ECTO:0000509). ECTO:0000509 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Hazard type: CHEMICAL
Route: ORAL
Bound to ECTO:0000509 exposure to drug, which is correct for this entry because this entry is the medicinal route. ECTO was searched through this repository's own adapter (sqlite:obo:ecto) for a colchicine-specific exposure class and none exists. ECTO:9000271 exposure to alkaloid also resolves; it is used on the plant-ingestion entry below rather than here, since that route is not a drug exposure. A term resolving in OLS would not be sufficient in either case, because dismech does not validate ECTO against OLS.
Exposure by two routes that differ in tempo but not in mechanism: an acute ingestion in self-harm or in error, and slow accumulation at prescribed doses when clearance falls. The second route is the one that catches clinicians out, because the prescription is correct and the patient is poisoned anyway.
Show evidence (1 reference)
PMID:36512928 SUPPORT Human Clinical
"Renal and hepatic dysfunction and medications that inhibit cytochrome P450 3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most significant risk factors."
Establishes the accumulation route - impaired clearance and interacting drugs - as the dominant risk setting for toxicity at ordinary doses.
Mechanism Target:
TRIGGERS Colchicine Exposure Exceeding the Therapeutic Window — Ingestion is what establishes the systemic burden the rest of the pathograph follows from.
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg."
Ties ingested dose to outcome, which is the exposure-to-burden step this link asserts.
Ingestion of a colchicine-containing plant
exposure to colchicine-containing plant material ECTO:9000271 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to colchicine-containing plant material, annotated with exposure to alkaloid (ECTO:9000271). ECTO:9000271 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Hazard type: CHEMICAL
Route: ORAL
Duration: ACUTE
Bound to ECTO:9000271 exposure to alkaloid rather than to ECTO:0000509 exposure to drug, because this route is not a medicinal exposure. Neither term is colchicine-specific; ECTO has no such class through this repository's adapter. The cited sources establish the plants as the source, the route as a recognised exposure history, and a case fatality of 10 percent in a 297-patient Gloriosa superba cohort. That figure is a population rate from one country's self-poisoning presentations and should not be read as a case fatality for plant ingestion generally.
Colchicine is a plant alkaloid, and poisoning also follows eating the plant that makes it - autumn crocus (Colchicum autumnale) or glory lily (Gloriosa superba). This route is not a medication error and does not involve a prescription at all, so nothing about drug interactions or renal clearance predicts it. The exposure history has to ask for it separately, which is why the diagnostic entry above names plants as a third history to take.
Show evidence (3 references)
PMID:20586571 SUPPORT Other
"History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis."
Records plant consumption alongside tablets and parenteral administration as a recognised exposure history, which is the basis for curating it as a separate route.
PMID:30888889 SUPPORT Human Clinical
"Gloriosa superba is a flowering plant that contains colchicine. Deliberate self-poisoning with this plant in Sri Lanka is common and potentially fatal."
Establishes the plant route as a common and lethal presentation in its own right, not an incidental one.
PMID:30888889 SUPPORT Human Clinical
"The case fatality was 10% (29/297), and death was much more common in older patients."
Gives a case fatality for the plant route from a 297-patient cohort, with an age effect. This is a population figure and is not comparable with the 14 to 26 percent range quoted elsewhere in this entry, which comes from published case reports of tablet overdose.
Mechanism Target:
TRIGGERS Colchicine Exposure Exceeding the Therapeutic Window — Eating the plant delivers the same alkaloid, so this route joins the pathograph at the same node as a tablet overdose. Nothing downstream distinguishes them.
Show evidence (1 reference)
PMID:36028733 SUPPORT Other
"Colchicine is a naturally occurring alkaloid extracted from the plants Colchicum autumnale and Gloriosa superba"
Identifies the two source plants and establishes that the compound in them is the same alkaloid, which is what lets this route share the downstream chain.
🔬

Diagnosis

3
Clinical recognition from exposure history and toxidrome
The diagnosis is made by putting an exposure history against a characteristic toxidrome. Both halves are needed - the toxidrome alone reads as gastroenteritis with shock, which is why the poisoning is missed in its first phase. The history must reach for three routes, not one: tablets, parenteral administration, and ingestion of colchicine-containing plants. Plasma colchicine concentration is measurable and strongly predicts death, but it is a prognostic measurement in a research cohort rather than a routinely available diagnostic test, and this entry does not curate it as one.
Show evidence (3 references)
PMID:20586571 SUPPORT Other
"History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis."
Names the three exposure histories that raise the diagnosis, which is the first half of this diagnostic approach.
PMID:20586571 SUPPORT Other
"Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia)."
Gives the toxidrome and pairs it with access to the drug, which is the second half.
PMID:30888889 SUPPORT Human Clinical
"Admission colchicine concentrations were highly correlated with a fatal outcome [median 7.8 ng/ml (IQR: 5.8-18.7) vs 1.2 (0-2.3) in survivors]."
Source for the measurable-concentration point in this description. The measurement was made by HPLC in a research cohort and predicts outcome; it is not curated here as a routine diagnostic test.
Recognition of colchicine neuromyopathy
A different diagnostic problem from the acute poisoning. The patient is on a correct prescription, the onset is insidious, and the available tests do not settle it. Recognition matters because stopping the drug resolved symptoms completely in 70 percent of reviewed cases, so the cost of missing it is weakness that need not have continued. Nearly half of the reviewed patients had been taking colchicine for over a year before the neuromyopathy was recognised.
Show evidence (4 references)
PMID:19078054 SUPPORT Other
"The symptoms of this disorder are frequently insidious, and the diagnostic tests used in its evaluation are mostly nonspecific."
States both the insidious onset and the nonspecificity of the available tests, which is the diagnostic difficulty this entry names.
PMID:19078054 SUPPORT Other
"Definitive diagnosis usually requires histologic examination where a characteristic vacuolar myopathy is typically present."
Identifies muscle biopsy as the definitive test and names the finding it looks for.
PMID:36512928 SUPPORT Human Clinical
"Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days."
Source for the 70 percent resolution figure in this description, which is what makes recognition worth the effort.
+ 1 more reference
Magnetic resonance imaging for biopsy targeting
MRI is used to pick the biopsy site rather than to make the diagnosis. The cited source is explicit that its value as a diagnostic modality in these patients is speculative, and this entry does not curate it as one.
Show evidence (1 reference)
PMID:19078054 SUPPORT Other
"Magnetic resonance imaging can be useful in the localization of optimal biopsy sites, although its use as a diagnostic modality in these patients is speculative."
Supports the localisation role and carries the author's own hedge about its diagnostic value, which is why this entry claims only the former.
📈

Progression

4
Gastrointestinal phase
Duration: approximately 10 to 24 hours after ingestion
Vomiting, abdominal pain and diarrhoea, indistinguishable from gastroenteritis. This is where the diagnosis is missed, and the review notes the phase can be absent altogether after intravenous administration - so its absence does not exclude the poisoning.
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration"
Gives the timing of this phase, the gastroenteritis resemblance, and the route-dependent exception.
Multi-organ dysfunction
Duration: 24 hours to 7 days after ingestion
The dangerous phase, and the one that follows an apparent improvement in the gastrointestinal symptoms. Marrow failure, cytopenias, sepsis, cardiac and renal injury. Death here is from multi-organ failure and sepsis rather than from any single organ.
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis."
Gives the interval and the mode of death for this phase.
Recovery
Duration: within a few weeks of ingestion
Recovery in survivors is generally complete, which is a meaningful feature of this poisoning: the lesion is a reversible binding event, not a permanent structural one, so a patient supported through the cytopenic phase can be expected to recover fully.
Show evidence (1 reference)
PMID:20586571 SUPPORT Other
"Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness."
States the timing and completeness of recovery.
Chronic-accumulation neuromyopathy
Duration: median 21 days to resolution after the drug is stopped
A separate time course belonging to the chronic route rather than to acute overdose. The systematic review found a mean total daily dose of 1.25 mg - that is a therapeutic dose - and 48 percent had been taking colchicine for more than twelve months before the neuromyopathy declared. Stopping the drug resolved symptoms completely in 70 percent, at a median of 21 days.
Show evidence (2 references)
PMID:36512928 SUPPORT Human Clinical
"The mean total daily dose was 1.25±0.60 mg and 48% had been taking colchicine for more than 12 months before presenting with neuromyopathy."
Gives the dose and the exposure duration this phase is defined by.
PMID:36512928 SUPPORT Human Clinical
"Cessation of colchicine generally led to complete resolution of symptoms in 70% of cases within a median of 21 days."
Gives the resolution proportion and the median time this phase's duration is taken from.
{ }

Source YAML

click to show 
name: Colchicine Poisoning
creation_date: '2026-09-01T22:30:00Z'
description: >-
  Colchicine poisoning follows exposure to a drug with a narrow therapeutic index
  and no clear boundary between a therapeutic, a toxic and a lethal dose. It
  arrives by three routes: acute overdose of the drug taken in self-harm or in
  error, slow accumulation at ordinary prescribed doses when renal or hepatic
  clearance falls or a CYP3A4 or P-glycoprotein inhibitor is co-prescribed, and
  ingestion of a colchicine-containing plant. All three converge on one molecular
  lesion. Colchicine binds tubulin and prevents
  microtubule assembly, and every downstream injury is an extension of that
  binding. The cells that depend most on the mitotic spindle fail first, so the
  gut mucosa and then the bone marrow give way, and it is the resulting
  pancytopenia with neutropenic sepsis that kills. The cells that depend on
  microtubule-based transport rather than on mitosis fail far more slowly,
  producing the proximal myopathy and accompanying peripheral neuropathy that
  characterise the chronic-accumulation route. One lesion, two tissues, two clocks. There is no
  antidote in routine clinical use.
categories:
- Toxic Exposure Disorder
- Treatment Toxicity
category: Complex
parents:
- Poisoning
disease_term:
  preferred_term: colchicine poisoning
  term:
    id: MONDO:0017859
    label: colchicine poisoning
pathophysiology:
- name: Colchicine Exposure Exceeding the Therapeutic Window
  description: >-
    Systemic colchicine burden above what the patient can tolerate, reached by a
    single large ingestion of tablets or plant material, or by accumulation at
    ordinary doses. The drug has no clear-cut boundary between nontoxic, toxic and
    lethal doses, which is why the routes are not usefully separated at the level
    of the exposure - the determinant is the concentration reached, not the size of
    any one dose.
  role: trigger
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It has a narrow therapeutic index, with no clear-cut distinction between
      nontoxic, toxic, and lethal doses, causing substantial confusion among
      clinicians.
    explanation: >-
      States the narrow index and the absence of a dose boundary, which is the
      claim this node rests on.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg.
      The lowest reported lethal doses of oral colchicine are 7-26 mg.
    explanation: >-
      Gives the acute-ingestion thresholds reported in the systematic review.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Admission colchicine concentrations were highly correlated with a fatal
      outcome [median 7.8 ng/ml (IQR: 5.8-18.7) vs 1.2 (0-2.3) in survivors].
    explanation: >-
      Ties measured concentration rather than ingested dose to outcome in a
      297-patient cohort, which is the basis for this node being defined by
      concentration reached.
  downstream:
  - target: Colchicine-Tubulin Binding and Microtubule Assembly Failure
    causal_link_type: DIRECT
    description: >-
      The systemic burden is what delivers colchicine to intracellular tubulin.
      Colchicine distributes very widely and binds intracellular elements, so the
      tissue concentration follows the systemic one closely.
    evidence:
    - reference: PMID:36028733
      reference_title: "Progress in the management of acute colchicine poisoning in adults."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Colchicine can spread rapidly and widely to all tissues shortly after oral
        administration, accumulating in bone marrow, kidney, heart, liver,
        intestinal mucosa, and brain
      explanation: >-
        Documents the wide tissue distribution, including to the bone marrow and
        intestinal mucosa this entry models as the first-affected tissues.
- name: Impaired Colchicine Clearance via CYP3A4 and P-Glycoprotein Inhibition
  description: >-
    Colchicine is metabolised by CYP3A4 and effluxed by P-glycoprotein, so a drug
    that inhibits either raises the concentration reached at an unchanged
    prescribed dose. Renal or hepatic impairment does the same thing by a
    different route. This is the mechanism behind the toxicity that appears at
    ordinary doses, and it is the reason a patient can be poisoned without ever
    taking an overdose.
  role: modifier
  biological_scale: MOLECULAR
  molecular_functions:
  - preferred_term: CYP3A4-mediated colchicine oxidation
    term:
      id: GO:0004497
      label: monooxygenase activity
    modifier: DECREASED
  biological_processes:
  - preferred_term: P-glycoprotein-mediated colchicine efflux
    term:
      id: GO:0042908
      label: xenobiotic transport
    modifier: DECREASED
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine is metabolized to 2- and 3-demethylcolchicine by the CYP 3A4
      isoform of cytochrome P450 in hepatocytes, followed by biliary excretion
    explanation: >-
      Establishes CYP3A4 as the metabolic route whose inhibition raises exposure.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin,
      erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can
      increase colchicine concentrations.
    explanation: >-
      Names the interacting inhibitors and states that they raise colchicine
      concentrations.
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In addition to CYP3A4, P-glycoprotein that is an ATPase efflux pump can
      extrude colchicine from the enterocytes to prevent gastrointestinal
      absorption
    explanation: >-
      Establishes the P-glycoprotein efflux arm this node names alongside CYP3A4,
      and locates it at the enterocyte, limiting absorption.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Co-administration with statins may increase the risk of myopathy.
    explanation: >-
      Names a specific co-medication risk for the myopathy arm of this entry. The
      source says "may increase the risk" and does not quantify it, so no
      magnitude is asserted.
  - reference: PMID:36688283
    reference_title: "Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The strongest ROR signal was for colchicine + atazanavir and
      rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6)
    explanation: >-
      Pharmacovigilance disproportionality signal linking a CYP3A4/P-gp inhibitor
      co-exposure to the myopathy this entry models downstream. A FAERS signal is
      a reporting association, not an incidence.
  downstream:
  - target: Colchicine Exposure Exceeding the Therapeutic Window
    causal_link_type: DIRECT
    description: >-
      Reduced clearance raises the concentration reached at an unchanged dose, so
      the interaction produces the exposure node rather than acting beside it.
    evidence:
    - reference: PMID:36688283
      reference_title: "Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Colchicine has a narrow therapeutic index. Its toxicity can be increased
        due to concomitant exposure to drugs inhibiting its metabolic pathway
      explanation: >-
        States that inhibiting the metabolic pathway increases toxicity, which is
        the direction of this edge.
  notes: >-
    Modelled as a modifier feeding the exposure node rather than as a second
    trigger, because the interaction does not injure anything by itself - it acts
    entirely by raising the concentration the patient reaches.
- name: Colchicine-Tubulin Binding and Microtubule Assembly Failure
  description: >-
    Colchicine binds tubulin dimers in roughly equimolar fashion and prevents them
    polymerising into microtubules. This is the same binding that makes the drug
    therapeutic at low dose, and the entire toxicity is a continuation of it - not
    a separate off-target effect. Microtubules serve both the mitotic spindle and
    intracellular transport, which is why one lesion produces two clinically
    distinct syndromes.
  role: central_effector
  biological_scale: MOLECULAR
  molecular_functions:
  - preferred_term: tubulin binding
    term:
      id: GO:0015631
      label: tubulin binding
  biological_processes:
  - preferred_term: microtubule polymerization
    term:
      id: GO:0046785
      label: microtubule polymerization
    modifier: DECREASED
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine's toxicity is an extension of its mechanism of action - binding
      to tubulin and disrupting the microtubular network.
    explanation: >-
      States both the binding target and that the toxicity is continuous with the
      therapeutic mechanism, which is the framing of this node.
  - reference: PMID:20661070
    reference_title: "Colchicine myopathy and neuromyopathy: two cases with different characteristics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Colchicine, a long established anti-inflammatory agent now used in several
      rheumatologic conditions, acts by inhibiting microtubular polymerization,
      as it binds equimolarly to tubulin molecules.
    explanation: >-
      Gives the stoichiometry and the polymerisation block underlying this node.
  - reference: PMID:34229452
    reference_title: "The Ugly Side of Colchicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The primary mechanism of action is binding to tubulins blocking the
      production and lengthening of microtubules, which make up the skeleton of
      cells.
    explanation: >-
      Independent statement of the same binding and assembly block.
  downstream:
  - target: Mitotic Arrest in Rapidly Proliferating Tissue
    causal_link_type: DIRECT
    description: >-
      Without assembling microtubules there is no mitotic spindle, so cells
      attempting division arrest. Tissues with the highest proliferative fraction
      therefore declare first.
    evidence:
    - reference: PMID:36028733
      reference_title: "Progress in the management of acute colchicine poisoning in adults."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        colchicine can impair mitosis by inhibiting microtubule devices which are
        necessary for the maintenance of cellular homeostasis and thereby causing
        cell injury
      explanation: >-
        Connects the microtubule block to mitotic impairment and cell injury.
  - target: Cardiac Myocyte Conduction and Contractility Failure
    causal_link_type: DIRECT
    description: >-
      The same microtubule collapse interrupts conduction and contractility in
      cardiac myocytes. This arm depends on neither mitosis nor axonal length, so
      it runs on the fast clock alongside the gut and marrow rather than with the
      neuromyopathy.
    evidence:
    - reference: PMID:20586571
      reference_title: "Colchicine poisoning: the dark side of an ancient drug."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        affected cells experience impaired protein assembly, decreased
        endocytosis and exocytosis, altered cell morphology, decreased cellular
        motility, arrest of mitosis, and interrupted cardiac myocyte conduction
        and contractility
      explanation: >-
        Names interrupted cardiac myocyte conduction and contractility as a direct
        cellular consequence of the microtubule lesion.
  - target: Microtubule-Dependent Intracellular Transport Failure
    causal_link_type: DIRECT
    description: >-
      The same assembly block removes the tracks for microtubule-based transport.
      This arm is independent of cell division, which is why it can affect
      post-mitotic muscle and nerve.
    evidence:
    - reference: PMID:20586571
      reference_title: "Colchicine poisoning: the dark side of an ancient drug."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        affected cells experience impaired protein assembly, decreased
        endocytosis and exocytosis, altered cell morphology, decreased cellular
        motility, arrest of mitosis, and interrupted cardiac myocyte conduction
        and contractility
      explanation: >-
        Lists the non-mitotic cellular consequences alongside mitotic arrest,
        establishing that the transport arm is a separate consequence of the same
        lesion.
- name: Mitotic Arrest in Rapidly Proliferating Tissue
  description: >-
    Cells attempting division without a spindle arrest and die. The tissues with
    the highest proliferative fraction - gut mucosa, bone marrow, hair follicle -
    are therefore the ones that declare first, and in that order clinically.
  role: intermediate
  biological_scale: CELLULAR
  conforms_to: "myelosuppression#Cytotoxic Insult to Proliferating Hematopoietic Progenitors"
  biological_processes:
  - preferred_term: mitotic cell cycle
    term:
      id: GO:0000278
      label: mitotic cell cycle
    modifier: DECREASED
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the organs with active cell proliferation, such as the gastrointestinal
      tract, bone marrow, and hair follicles, are often the most susceptible to
      the toxic effects of colchicine
    explanation: >-
      Names the proliferative tissues that this node predicts will be affected
      first, and states the reason as their proliferation.
  downstream:
  - target: Gastrointestinal Mucosal Injury
    causal_link_type: DIRECT
    description: >-
      The intestinal epithelium turns over faster than any other tissue here, so
      it fails earliest - within the first day, before the marrow.
  - target: Hepatic and Renal Injury
    causal_link_type: DIRECT
    description: >-
      The review attributes the hepatic and renal dysfunction to the same
      inhibition of mitosis, which is why this injury is placed downstream of the
      arrest node rather than treated as a separate toxic mechanism.
    evidence:
    - reference: PMID:36028733
      reference_title: "Progress in the management of acute colchicine poisoning in adults."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        colchicine overdose can lead to multiple organ dysfunction by inhibiting
        cell mitosis progress, particularly in the liver and kidneys
      explanation: >-
        Names the liver and kidneys specifically as organs injured through the
        mitotic mechanism, which is the direction of this edge.
  - target: Bone Marrow Hematopoietic Suppression
    causal_link_type: DIRECT
    description: >-
      Haematopoietic progenitors arrest, and the marrow's output falls. The delay
      before this becomes visible in the blood is the transit time of the
      circulating cells already made, not a delay in the injury itself.
    evidence:
    - reference: PMID:7530779
      reference_title: "Colchicine toxicity--clinical features and treatment. Massive overdose case report."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        She developed multiple organ failure and bone marrow suppression after
        the suicidal ingestion of 50 (1 mg) colchicine tablets.
      explanation: >-
        Reports marrow suppression following a quantified colchicine ingestion.
  notes: >-
    Conformance is asserted on the shared step of a cytotoxic insult acting on
    dividing haematopoietic progenitors. The module's trigger is written for
    chemotherapy and radiation; colchicine reaches the same node by spindle
    poisoning rather than by DNA damage, which is a mechanistically different
    insult with the same target population of cells.
- name: Gastrointestinal Mucosal Injury
  description: >-
    Injury to the rapidly renewing intestinal epithelium, producing the vomiting,
    abdominal pain and profuse diarrhoea that open the illness. Clinically this is
    the phase that looks like gastroenteritis, and it is where the poisoning is
    most often missed.
  role: intermediate
  biological_scale: TISSUE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Acute colchicine poisoning can lead to original gastrointestinal disorders,
      shock, progressive multiple organ failure, and myelosuppression.
    explanation: >-
      Places the gastrointestinal disturbance first in the sequence this node
      occupies.
  downstream:
  - target: Neutropenic Sepsis and Progressive Multi-Organ Failure
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Fluid and electrolyte loss from the mucosal injury produces hypovolaemia and
      shock, which is one of the components of the terminal multi-organ picture.
      The intermediates are volume depletion and hypoperfusion.
    evidence:
    - reference: PMID:36028733
      reference_title: "Progress in the management of acute colchicine poisoning in adults."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Acute colchicine poisoning can lead to original gastrointestinal
        disorders, shock, progressive multiple organ failure, and myelosuppression.
      explanation: >-
        Places gastrointestinal disturbance, shock and multi-organ failure in the
        sequence this edge asserts. The source lists them in order; it does not
        separately demonstrate that the gastrointestinal fluid loss is what causes
        the shock.
- name: Bone Marrow Hematopoietic Suppression
  description: >-
    Failure of marrow output across all three lineages once dividing progenitors
    are arrested. This is the step that makes colchicine poisoning lethal rather
    than merely severe, and it is why the second phase of the illness is the
    dangerous one even when the patient looks better than they did on day one.
  role: central_effector
  biological_scale: TISSUE
  conforms_to: "myelosuppression#Bone Marrow Hematopoietic Suppression"
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Acute colchicine poisoning can lead to original gastrointestinal disorders,
      shock, progressive multiple organ failure, and myelosuppression.
    explanation: >-
      Names myelosuppression as a consequence of acute colchicine poisoning.
  downstream:
  - target: Multilineage Peripheral Cytopenias
    causal_link_type: DIRECT
    description: >-
      Marrow failure shows in the blood as the existing circulating cells are
      consumed and not replaced, so the cytopenia lags the marrow injury by
      roughly the lifespan of each lineage.
    evidence:
    - reference: PMID:1384817
      reference_title: "Use of granulocyte colony-stimulating factor in the treatment of pancytopenia secondary to colchicine overdose."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        A 19-year-old man developed pancytopenia four days after ingestion of
        approximately 50-60 0.6-mg colchicine tablets in a suicide attempt.
      explanation: >-
        Documents pancytopenia and its several-day delay after a quantified
        ingestion, which is the lag this edge describes.
- name: Multilineage Peripheral Cytopenias
  description: >-
    Pancytopenia, with neutropenia the component that matters. Anaemia and
    thrombocytopenia follow on their own slower timescales, and the coagulopathy
    seen in severe cases is not purely a platelet problem - disseminated
    intravascular coagulation is reported alongside it.
  role: intermediate
  biological_scale: ORGANISM
  conforms_to: "myelosuppression#Multilineage Peripheral Cytopenias"
  evidence:
  - reference: PMID:34229452
    reference_title: "The Ugly Side of Colchicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He developed progressive multiple organ failure with shock, acute kidney
      failure, troponemia, pancytopenia, absolute neutropenia, disseminated
      intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic
      acidosis.
    explanation: >-
      Documents pancytopenia with absolute neutropenia, and the disseminated
      intravascular coagulation this node's description separates from
      thrombocytopenia.
  downstream:
  - target: Neutropenic Sepsis and Progressive Multi-Organ Failure
    causal_link_type: DIRECT
    description: >-
      Loss of neutrophils removes the defence against infection in a patient
      whose gut mucosal barrier is already injured, so the two arms of the
      poisoning compound each other. Positive blood cultures were recorded in 5 of
      20 patients in the cited series; the route of entry was not established
      there, so no claim of bacterial translocation is made.
    evidence:
    - reference: PMID:20586571
      reference_title: "Colchicine poisoning: the dark side of an ancient drug."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        24 h to 7 days after ingestion - multi-organ dysfunction. Death results
        from rapidly progressive multi-organ failure and sepsis.
      explanation: >-
        States that death follows multi-organ failure and sepsis in the phase
        this edge covers.
- name: Neutropenic Sepsis and Progressive Multi-Organ Failure
  description: >-
    The terminal phase: sepsis in a patient with no neutrophils, on a background
    of shock, acute kidney injury, hepatic failure, rhabdomyolysis and lactic
    acidosis. Reported case-fatality in acute poisoning runs to a quarter of
    patients.
  role: outcome
  biological_scale: ORGANISM
  conforms_to: "myelosuppression#Cytopenia-Related Clinical Complications"
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the fatality rate of acute colchicine poisoning may range from 14.3 to
      25.6%
    explanation: >-
      Gives the reported case-fatality range this node states.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The culmination of these mechanisms leads to multi-organ dysfunction and
      failure.
    explanation: >-
      States multi-organ failure as the endpoint of the mechanisms above.
- name: Microtubule-Dependent Intracellular Transport Failure
  description: >-
    Loss of the microtubule tracks on which intracellular cargo moves. In muscle
    and in long peripheral axons this matters more than mitosis does, because
    those cells are post-mitotic and depend on transport over distances no other
    mechanism can cover. This arm is slower than the marrow arm and is what
    dominates the chronic-accumulation route.
  role: intermediate
  biological_scale: CELLULAR
  conforms_to: "peripheral_axonal_degeneration#Axonal Transport Impairment and Mitochondrial Dysfunction"
  biological_processes:
  - preferred_term: microtubule-based transport
    term:
      id: GO:0099111
      label: microtubule-based transport
    modifier: DECREASED
  evidence:
  - reference: PMID:20661070
    reference_title: "Colchicine myopathy and neuromyopathy: two cases with different characteristics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cytoskeletal microtubules are crucial in processes of cell viability, such
      as mitosis and intracellular vesicle motility.
    explanation: >-
      Names intracellular vesicle motility alongside mitosis as a microtubule
      function, which is the division this node depends on. The statement is
      about microtubule function generally rather than about axons specifically.
  downstream:
  - target: Colchicine Neuromyopathy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Transport failure in myocytes and in peripheral axons produces the vacuolar
      myopathy and the accompanying axonal neuropathy. The intermediates -
      lysosomal accumulation in the vacuolar myopathy, distal axonal degeneration
      in the neuropathy - are described in the clinical literature, so the link is
      not direct.
    evidence:
    - reference: PMID:19078054
      reference_title: "Colchicine neuromyopathy."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Definitive diagnosis usually requires histologic examination where a
        characteristic vacuolar myopathy is typically present.
      explanation: >-
        Establishes the vacuolar histology that this edge names as the muscle
        endpoint.
  notes: >-
    Conformance to the module's axonal-transport node is asserted on the transport
    arm only. The module node also carries mitochondrial dysfunction; this entry
    makes no mitochondrial claim for colchicine, because none of the cited human
    sources reports one. Note also the direction of the evidence here: the cited
    statements are about microtubule function in general, and the specifically
    axonal reading is inference from the clinical neuropathy, not a direct
    measurement of axonal transport in a poisoned patient.
- name: Colchicine Neuromyopathy
  description: >-
    Proximal myopathy with elevated creatine kinase, accompanied in about half of
    reported cases by a peripheral neuropathy. It is characteristically insidious,
    arises at ordinary therapeutic doses rather than in overdose, and resolves on
    stopping the drug - which is what separates it from the acute poisoning
    syndrome and makes recognising it worthwhile.
  role: outcome
  biological_scale: TISSUE
  conforms_to: "peripheral_axonal_degeneration#Distal Axonal Degeneration and Demyelination"
  evidence:
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 143 cases of neuromyopathy from 99 articles were identified as
      having a "definite" or "probable" association with colchicine usage
    explanation: >-
      Establishes the entity and its size in the published literature by
      systematic review.
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most of these cases presented with features of both neuropathy and myopathy
    explanation: >-
      Supports the combined neuropathy-and-myopathy presentation this node
      describes. It establishes co-occurrence only; it does not characterise the
      fibre pathology as axonal, and the node notes record that limit.
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine myopathy can complicate standard treatment of gout, especially
      in those patients with underlying renal insufficiency.
    explanation: >-
      States that the myopathy arises during standard treatment and is
      potentiated by renal impairment, which is the chronic-accumulation route.
  notes: >-
    Conformance is asserted at the level of a toxic peripheral neuromyopathy
    reaching the module's degeneration node. The module node names axonal
    degeneration and demyelination; the sources cited here establish a
    colchicine-associated neuropathy co-occurring with myopathy but do not
    themselves classify the fibre pathology, and the predominant finding in the
    systematic review is myopathic rather than neuropathic. The conformance should
    be read as partial on that basis.
- name: Hepatic and Renal Injury
  description: >-
    Injury to the two organs that clear colchicine. This node matters less for the
    organ failure it names than for what it does to the rest of the pathograph:
    hepatic elimination carries most of the drug's clearance, so damaging the liver
    slows removal of the poison doing the damage. The loop is why late presentation
    and pre-existing hepatic or renal impairment carry a worse prognosis.
  role: intermediate
  biological_scale: TISSUE
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine and its metabolites are mainly eliminated through the liver. The
      kidneys contribute only 10–20% of the total colchicine clearance
    explanation: >-
      Establishes that clearance is predominantly hepatic, which is what makes
      liver injury a rate-limiting step for elimination rather than only an organ
      failure.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Delayed presentation, pre-existing renal or liver impairment are associated
      with poor prognosis.
    explanation: >-
      Links pre-existing hepatic and renal impairment to worse outcome, which is
      the prognostic consequence of this node.
  downstream:
  - target: Colchicine Exposure Exceeding the Therapeutic Window
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Injury to the clearing organs slows elimination and so raises the systemic
      burden, closing a positive feedback loop back onto the head of the
      pathograph. The intermediate is reduced hepatic metabolism and biliary
      excretion.
    evidence:
    - reference: PMID:34229452
      reference_title: "The Ugly Side of Colchicine."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        With our patient having both liver and kidneys impairment, this could
        have led to his progression of MOF
      explanation: >-
        The authors propose that combined hepatic and renal impairment drove
        progression in their case. Note the hedge in the source - "could have led
        to" - so this is an author's mechanistic proposal about one patient, not a
        measured demonstration of impaired clearance.
- name: Cardiac Myocyte Conduction and Contractility Failure
  description: >-
    Interruption of conduction and contractility in cardiac muscle, giving
    arrhythmia and depressed contractility. This is the organ dysfunction most
    frequently recorded in the published adult case series, and it is not a
    proliferation effect - cardiac myocytes are post-mitotic, so this arm shows
    that the poisoning is not only a spindle poison.
  role: intermediate
  biological_scale: TISSUE
  cell_types:
  - preferred_term: cardiac myocyte
    term:
      id: CL:0000746
      label: cardiac muscle cell
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Organ dysfunction, n (%) Acute myocardial injury16 (80%) Acidosis14 (70%)
      Acute kidney injury15 (75%)
    explanation: >-
      Records acute myocardial injury in 16 of 20 patients, the most frequent
      organ dysfunction in that published series. The denominator is a series of
      published case reports and skews severe, so no frequency band is asserted.
  downstream:
  - target: Neutropenic Sepsis and Progressive Multi-Organ Failure
    causal_link_type: DIRECT
    description: >-
      Cardiac failure contributes to the shock state that defines the terminal
      phase, alongside the septic and hypovolaemic components.
phenotypes:
- name: Diarrhea
  description: >-
    Profuse diarrhoea in the opening gastrointestinal phase, part of the picture
    that mimics gastroenteritis.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
    temporality: ACUTE
  frequency: FREQUENT
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1
      (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)
    explanation: >-
      Reports diarrhoea in 14 of 20 patients. The denominator is a series of 20
      published adult case reports, which skews towards severe poisoning; the
      FREQUENT band is taken as a conservative reading of that figure rather than
      as a population frequency.
- name: Vomiting
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
    temporality: ACUTE
  frequency: FREQUENT
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1
      (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)
    explanation: >-
      Reports vomiting in 14 of 20 patients in the same published series, with the
      same denominator caveat.
- name: Abdominal pain
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
    temporality: ACUTE
  frequency: FREQUENT
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinical symptoms, n (%) Abdominal pain14 (70%) Diarrhea14 (70%) Dizziness1
      (5%) Nausea8 (40%) Shock1 (5%) Vomiting14 (70%)
    explanation: >-
      Reports abdominal pain in 14 of 20 patients, same series and same caveat.
- name: Pancytopenia
  description: >-
    Fall across all three lineages, appearing in the second phase.
  phenotype_term:
    preferred_term: Pancytopenia
    term:
      id: HP:0001876
      label: Pancytopenia
    temporality: ACUTE
  evidence:
  - reference: PMID:34229452
    reference_title: "The Ugly Side of Colchicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He developed progressive multiple organ failure with shock, acute kidney
      failure, troponemia, pancytopenia, absolute neutropenia, disseminated
      intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic
      acidosis.
    explanation: >-
      Documents pancytopenia in a case of acute colchicine poisoning. No frequency
      band is asserted, because the published series available here over-represent
      severe poisoning.
- name: Decreased total neutrophil count
  description: >-
    Neutropenia is the component of the pancytopenia that determines outcome, and
    the reason G-CSF is given.
  phenotype_term:
    preferred_term: Neutropenia
    term:
      id: HP:0001875
      label: Decreased total neutrophil count
    temporality: ACUTE
  evidence:
  - reference: PMID:34229452
    reference_title: "The Ugly Side of Colchicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He developed progressive multiple organ failure with shock, acute kidney
      failure, troponemia, pancytopenia, absolute neutropenia, disseminated
      intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic
      acidosis.
    explanation: >-
      Documents absolute neutropenia in acute colchicine poisoning.
- name: Thrombocytopenia
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
    temporality: ACUTE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%)
      Thrombocytopenia12 (60%)
    explanation: >-
      Reports thrombocytopenia in 12 of 20 patients in the published series. No
      band is asserted from this denominator.
- name: Anemia
  phenotype_term:
    preferred_term: Anemia
    term:
      id: HP:0001903
      label: Anemia
    temporality: ACUTE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Anemia8 (40%) Coagulation disorders15 (75%)
    explanation: >-
      Reports anaemia in 8 of 20 patients in the published series.
- name: Acute kidney injury
  phenotype_term:
    preferred_term: Acute kidney injury
    term:
      id: HP:0001919
      label: Acute kidney injury
    temporality: ACUTE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Organ dysfunction, n (%) Acute myocardial injury16 (80%) Acidosis14 (70%)
      Acute kidney injury15 (75%)
    explanation: >-
      Reports acute kidney injury in 15 of 20 patients in the published series.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and
      rhabdomyolysis.
    explanation: >-
      Qualifies the severity of this phenotype by exposure route: it was mild in a
      297-patient plant-ingestion cohort, against the severe injury reported in
      tablet overdose. The phenotype is route-dependent and the entry should not
      be read as asserting one severity.
- name: Rhabdomyolysis
  phenotype_term:
    preferred_term: Rhabdomyolysis
    term:
      id: HP:0003201
      label: Rhabdomyolysis
    temporality: ACUTE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%)
      Thrombocytopenia12 (60%)
    explanation: >-
      Reports rhabdomyolysis in 9 of 20 patients in the published series.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and
      rhabdomyolysis.
    explanation: >-
      Qualifies the severity of this phenotype by exposure route: it was mild in a
      297-patient plant-ingestion cohort, against the severe injury reported in
      tablet overdose. The phenotype is route-dependent and the entry should not
      be read as asserting one severity.
- name: Lactic acidosis
  phenotype_term:
    preferred_term: Lactic acidosis
    term:
      id: HP:0003128
      label: Lactic acidosis
    temporality: ACUTE
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine poisoning should be suspected in patients with access to the drug
      and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis,
      and prerenal azotemia).
    explanation: >-
      Names lactic acidosis as part of the characteristic toxidrome.
- name: Hypotension
  phenotype_term:
    preferred_term: Hypotension
    term:
      id: HP:0002615
      label: Hypotension
    temporality: ACUTE
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine poisoning should be suspected in patients with access to the drug
      and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis,
      and prerenal azotemia).
    explanation: >-
      Names hypotension as part of the characteristic toxidrome.
- name: Decreased liver function
  phenotype_term:
    preferred_term: Hepatic injury
    term:
      id: HP:0001410
      label: Decreased liver function
    temporality: ACUTE
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Leucopenia11 (55%) Liver damage12 (60%) Rhabdomyolysis9 (45%)
      Thrombocytopenia12 (60%)
    explanation: >-
      Reports liver damage in 12 of 20 patients in the published series.
- name: Proximal muscle weakness
  description: >-
    The predominant presenting feature of the chronic-accumulation neuromyopathy.
  phenotype_term:
    preferred_term: Proximal muscle weakness
    term:
      id: HP:0003701
      label: Proximal muscle weakness
    temporality: CHRONIC
  evidence:
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cases generally present with proximal myopathy symptoms.
    explanation: >-
      States proximal myopathy as the general presentation across 143 systematically
      reviewed cases.
- name: Peripheral neuropathy
  description: >-
    Accompanies the myopathy in about half of reported neuromyopathy cases.
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
    temporality: CHRONIC
  evidence:
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most of these cases presented with features of both neuropathy and myopathy
    explanation: >-
      Establishes that neuropathy co-occurs with myopathy in the majority of the
      143 reviewed cases.
- name: Alopecia
  description: >-
    Hair loss in survivors, from arrest of the follicular matrix, appearing during
    the recovery phase.
  phenotype_term:
    preferred_term: Alopecia
    term:
      id: HP:0001596
      label: Alopecia
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the organs with active cell proliferation, such as the gastrointestinal
      tract, bone marrow, and hair follicles, are often the most susceptible to
      the toxic effects of colchicine
    explanation: >-
      Names the hair follicle as a susceptible proliferative tissue. This supports
      the mechanism; it is not a direct report of alopecia frequency, and no
      frequency band is asserted.
diagnosis:
- name: Clinical recognition from exposure history and toxidrome
  description: >-
    The diagnosis is made by putting an exposure history against a characteristic
    toxidrome. Both halves are needed - the toxidrome alone reads as gastroenteritis
    with shock, which is why the poisoning is missed in its first phase. The history
    must reach for three routes, not one: tablets, parenteral administration, and
    ingestion of colchicine-containing plants. Plasma colchicine concentration is
    measurable and strongly predicts death, but it is a prognostic measurement in a
    research cohort rather than a routinely available diagnostic test, and this
    entry does not curate it as one.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      History of ingestion of tablets, parenteral administration, or consumption
      of colchicine-containing plants suggest the diagnosis.
    explanation: >-
      Names the three exposure histories that raise the diagnosis, which is the
      first half of this diagnostic approach.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine poisoning should be suspected in patients with access to the drug
      and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis,
      and prerenal azotemia).
    explanation: >-
      Gives the toxidrome and pairs it with access to the drug, which is the
      second half.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Admission colchicine concentrations were highly correlated with a fatal
      outcome [median 7.8 ng/ml (IQR: 5.8-18.7) vs 1.2 (0-2.3) in survivors].
    explanation: >-
      Source for the measurable-concentration point in this description. The
      measurement was made by HPLC in a research cohort and predicts outcome; it
      is not curated here as a routine diagnostic test.
- name: Recognition of colchicine neuromyopathy
  description: >-
    A different diagnostic problem from the acute poisoning. The patient is on a
    correct prescription, the onset is insidious, and the available tests do not
    settle it. Recognition matters because stopping the drug resolved symptoms
    completely in 70 percent of reviewed cases, so the cost of missing it is
    weakness that need not have continued. Nearly half of the reviewed patients had
    been taking colchicine for over a year before the neuromyopathy was recognised.
  evidence:
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The symptoms of this disorder are frequently insidious, and the diagnostic
      tests used in its evaluation are mostly nonspecific.
    explanation: >-
      States both the insidious onset and the nonspecificity of the available
      tests, which is the diagnostic difficulty this entry names.
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Definitive diagnosis usually requires histologic examination where a
      characteristic vacuolar myopathy is typically present.
    explanation: >-
      Identifies muscle biopsy as the definitive test and names the finding it
      looks for.
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cessation of colchicine generally led to complete resolution of symptoms in
      70% of cases within a median of 21 days.
    explanation: >-
      Source for the 70 percent resolution figure in this description, which is
      what makes recognition worth the effort.
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The mean total daily dose was 1.25±0.60 mg and 48% had been taking
      colchicine for more than 12 months before presenting with neuromyopathy.
    explanation: >-
      Source for the delay-to-recognition figure in this description, and for the
      point that the dose involved is a therapeutic one.
- name: Magnetic resonance imaging for biopsy targeting
  description: >-
    MRI is used to pick the biopsy site rather than to make the diagnosis. The
    cited source is explicit that its value as a diagnostic modality in these
    patients is speculative, and this entry does not curate it as one.
  evidence:
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Magnetic resonance imaging can be useful in the localization of optimal
      biopsy sites, although its use as a diagnostic modality in these patients is
      speculative.
    explanation: >-
      Supports the localisation role and carries the author's own hedge about its
      diagnostic value, which is why this entry claims only the former.
histopathology:
- name: Vacuolar myopathy
  description: >-
    Vacuolar change in muscle on biopsy, the characteristic finding sought when
    the diagnosis needs settling. The source says it is typically present, not
    invariably, so it is not curated as a required feature. It is the
    tissue-level correlate of the transport-failure arm rather than of the mitotic
    arm.
  diagnostic: true
  evidence:
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Definitive diagnosis usually requires histologic examination where a
      characteristic vacuolar myopathy is typically present.
    explanation: >-
      States the characteristic histology and its role in definitive diagnosis.
progression:
- phase: Gastrointestinal phase
  duration: approximately 10 to 24 hours after ingestion
  notes: >-
    Vomiting, abdominal pain and diarrhoea, indistinguishable from gastroenteritis.
    This is where the diagnosis is missed, and the review notes the phase can be
    absent altogether after intravenous administration - so its absence does not
    exclude the poisoning.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis
      may be absent after intravenous administration
    explanation: >-
      Gives the timing of this phase, the gastroenteritis resemblance, and the
      route-dependent exception.
- phase: Multi-organ dysfunction
  duration: 24 hours to 7 days after ingestion
  notes: >-
    The dangerous phase, and the one that follows an apparent improvement in the
    gastrointestinal symptoms. Marrow failure, cytopenias, sepsis, cardiac and
    renal injury. Death here is from multi-organ failure and sepsis rather than
    from any single organ.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      24 h to 7 days after ingestion - multi-organ dysfunction. Death results from
      rapidly progressive multi-organ failure and sepsis.
    explanation: >-
      Gives the interval and the mode of death for this phase.
- phase: Recovery
  duration: within a few weeks of ingestion
  notes: >-
    Recovery in survivors is generally complete, which is a meaningful feature of
    this poisoning: the lesion is a reversible binding event, not a permanent
    structural one, so a patient supported through the cytopenic phase can be
    expected to recover fully.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Recovery typically occurs within a few weeks of ingestion, and is generally
      a complete recovery barring complications of the acute illness.
    explanation: >-
      States the timing and completeness of recovery.
- phase: Chronic-accumulation neuromyopathy
  duration: median 21 days to resolution after the drug is stopped
  notes: >-
    A separate time course belonging to the chronic route rather than to acute
    overdose. The systematic review found a mean total daily dose of 1.25 mg -
    that is a therapeutic dose - and 48 percent had been taking colchicine for
    more than twelve months before the neuromyopathy declared. Stopping the drug
    resolved symptoms completely in 70 percent, at a median of 21 days.
  evidence:
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The mean total daily dose was 1.25±0.60 mg and 48% had been taking
      colchicine for more than 12 months before presenting with neuromyopathy.
    explanation: >-
      Gives the dose and the exposure duration this phase is defined by.
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cessation of colchicine generally led to complete resolution of symptoms in
      70% of cases within a median of 21 days.
    explanation: >-
      Gives the resolution proportion and the median time this phase's duration is
      taken from.
environmental:
- name: Colchicine exposure above the therapeutic window
  description: >-
    Exposure by two routes that differ in tempo but not in mechanism: an acute
    ingestion in self-harm or in error, and slow accumulation at prescribed doses
    when clearance falls. The second route is the one that catches clinicians out,
    because the prescription is correct and the patient is poisoned anyway.
  exposure_term:
    preferred_term: exposure to colchicine
    term:
      id: ECTO:0000509
      label: exposure to drug
  exposure_classifications:
    hazard_agent_type:
    - classification_value: CHEMICAL
    exposure_route:
    - classification_value: ORAL
  influences_mechanisms:
  - target: Colchicine Exposure Exceeding the Therapeutic Window
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Ingestion is what establishes the systemic burden the rest of the pathograph
      follows from.
    evidence:
    - reference: PMID:20586571
      reference_title: "Colchicine poisoning: the dark side of an ancient drug."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        High fatality rate was reported after acute ingestions exceeding 0.5
        mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.
      explanation: >-
        Ties ingested dose to outcome, which is the exposure-to-burden step this
        link asserts.
  evidence:
  - reference: PMID:36512928
    reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Renal and hepatic dysfunction and medications that inhibit cytochrome P450
      3A4 isozyme (CYP3A4) and P-glycoprotein (P-gp) appear to be the most
      significant risk factors.
    explanation: >-
      Establishes the accumulation route - impaired clearance and interacting
      drugs - as the dominant risk setting for toxicity at ordinary doses.
  notes: >-
    Bound to ECTO:0000509 exposure to drug, which is correct for this entry
    because this entry is the medicinal route. ECTO was searched through this
    repository's own adapter (sqlite:obo:ecto) for a colchicine-specific exposure
    class and none exists. ECTO:9000271 exposure to alkaloid also resolves; it is
    used on the plant-ingestion entry below rather than here, since that route is
    not a drug exposure. A term resolving in OLS would not be sufficient in either
    case, because dismech does not validate ECTO against OLS.
- name: Ingestion of a colchicine-containing plant
  description: >-
    Colchicine is a plant alkaloid, and poisoning also follows eating the plant
    that makes it - autumn crocus (Colchicum autumnale) or glory lily (Gloriosa
    superba). This route is not a medication error and does not involve a
    prescription at all, so nothing about drug interactions or renal clearance
    predicts it. The exposure history has to ask for it separately, which is why
    the diagnostic entry above names plants as a third history to take.
  exposure_term:
    preferred_term: exposure to colchicine-containing plant material
    term:
      id: ECTO:9000271
      label: exposure to alkaloid
  exposure_classifications:
    hazard_agent_type:
    - classification_value: CHEMICAL
    exposure_route:
    - classification_value: ORAL
    exposure_duration:
    - classification_value: ACUTE
  influences_mechanisms:
  - target: Colchicine Exposure Exceeding the Therapeutic Window
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Eating the plant delivers the same alkaloid, so this route joins the
      pathograph at the same node as a tablet overdose. Nothing downstream
      distinguishes them.
    evidence:
    - reference: PMID:36028733
      reference_title: "Progress in the management of acute colchicine poisoning in adults."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Colchicine is a naturally occurring alkaloid extracted from the plants
        Colchicum autumnale and Gloriosa superba
      explanation: >-
        Identifies the two source plants and establishes that the compound in them
        is the same alkaloid, which is what lets this route share the downstream
        chain.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      History of ingestion of tablets, parenteral administration, or consumption
      of colchicine-containing plants suggest the diagnosis.
    explanation: >-
      Records plant consumption alongside tablets and parenteral administration as
      a recognised exposure history, which is the basis for curating it as a
      separate route.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Gloriosa superba is a flowering plant that contains colchicine. Deliberate
      self-poisoning with this plant in Sri Lanka is common and potentially fatal.
    explanation: >-
      Establishes the plant route as a common and lethal presentation in its own
      right, not an incidental one.
  - reference: PMID:30888889
    reference_title: "Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The case fatality was 10% (29/297), and death was much more common in older
      patients.
    explanation: >-
      Gives a case fatality for the plant route from a 297-patient cohort, with an
      age effect. This is a population figure and is not comparable with the 14 to
      26 percent range quoted elsewhere in this entry, which comes from published
      case reports of tablet overdose.
  notes: >-
    Bound to ECTO:9000271 exposure to alkaloid rather than to ECTO:0000509
    exposure to drug, because this route is not a medicinal exposure. Neither term
    is colchicine-specific; ECTO has no such class through this repository's
    adapter. The cited sources establish the plants as the source, the route as a
    recognised exposure history, and a case fatality of 10 percent in a
    297-patient Gloriosa superba cohort. That figure is a population rate from one
    country's self-poisoning presentations and should not be read as a case
    fatality for plant ingestion generally.
treatments:
- name: Granulocyte colony-stimulating factor
  description: >-
    G-CSF is given to shorten the neutropenic phase. It does not oppose the
    tubulin lesion and it cannot restart a progenitor that is arrested; it acts on
    the marrow's output once the drug is clearing, which is why it is described as
    supportive rather than as an antidote. It is the one pharmacological measure
    here that is aimed at a specific node of this pathograph.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: filgrastim
      term:
        id: NCIT:C1474
        label: Filgrastim
  target_mechanisms:
  - target: Bone Marrow Hematopoietic Suppression
    treatment_effect: MODULATES
    description: >-
      Stimulates granulopoiesis to shorten the period of neutropenia. Recorded as
      MODULATES rather than RESTORES because the cited reports describe recovery
      of counts under treatment, not a demonstrated reversal of the marrow lesion
      against a control.
    evidence:
    - reference: PMID:1384817
      reference_title: "Use of granulocyte colony-stimulating factor in the treatment of pancytopenia secondary to colchicine overdose."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        His pancytopenia resolved after subcutaneous administration of one
        300-micrograms dose of G-CSF.
      explanation: >-
        Reports resolution of the cytopenia after G-CSF in a single case. A single
        uncontrolled case cannot separate the drug's effect from spontaneous
        marrow recovery, which is why the effect is graded MODULATES.
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Supportive treatments including administration of granulocyte
      colony-stimulating factor are the mainstay of treatment.
    explanation: >-
      Establishes G-CSF within supportive care as the mainstay, which is the role
      this entry gives it.
  - reference: PMID:7530779
    reference_title: "Colchicine toxicity--clinical features and treatment. Massive overdose case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The pancytopenia responded to granulocyte colony-stimulating factor 300
      micrograms on days 4, 5, 6, and 8.
    explanation: >-
      A second case reporting response of the pancytopenia to G-CSF, with the
      dosing schedule.
  notes: >-
    therapeutic_modality is OTHER rather than SMALL_MOLECULE: filgrastim is a
    recombinant protein, and the schema has no cytokine or growth-factor value.
- name: Activated charcoal
  description: >-
    Gastrointestinal decontamination. Colchicine undergoes significant
    enterohepatic recirculation, which is a specific argument for charcoal here
    beyond the generic one, though the cited review recommends it on timing
    grounds without invoking that. The same recommendation reserves gastric lavage
    for very large ingestions presenting within an hour, so lavage is a narrow
    adjunct to charcoal rather than a separate treatment, and it is not curated as
    one.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
    therapeutic_agent:
    - preferred_term: activated charcoal
      term:
        id: CHEBI:91090
        label: charcoal
  evidence:
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Timely gastrointestinal decontamination should be considered with activated
      charcoal, and very large, recent (<60 min) ingestions may warrant gastric
      lavage.
    explanation: >-
      States the decontamination recommendation and its timing constraint.
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Colchicine and its metabolites undergo significant enterohepatic
      re-circulation which may further lead to its retention in the body
    explanation: >-
      Documents the enterohepatic recirculation this entry names as an additional
      argument for charcoal. The source states the recirculation, not that
      charcoal interrupts it.
- name: Withdrawal of colchicine and of interacting drugs
  description: >-
    For the chronic-accumulation neuromyopathy this is the treatment, and it
    works: symptoms resolved completely in 70 percent of reviewed cases at a
    median of 21 days. Rechallenge at a reduced dose was usually tolerated, which
    matters clinically for patients with familial Mediterranean fever who have few
    alternatives.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_mechanisms:
  - target: Colchicine Exposure Exceeding the Therapeutic Window
    treatment_effect: INHIBITS
    description: >-
      Stopping the drug removes the exposure at the head of the pathograph, which
      is why the downstream neuromyopathy reverses.
    evidence:
    - reference: PMID:36512928
      reference_title: "Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Cessation of colchicine generally led to complete resolution of symptoms
        in 70% of cases within a median of 21 days.
      explanation: >-
        Demonstrates that removing the exposure reverses the downstream syndrome,
        which is the claim of this link.
  evidence:
  - reference: PMID:19078054
    reference_title: "Colchicine neuromyopathy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is important to be aware of this entity, as the discontinuation of
      colchicine will allow a prompt remission.
    explanation: >-
      States discontinuation as the effective intervention for the myopathy.
- name: Intensive supportive care
  description: >-
    Mechanical ventilation, vasopressors, renal replacement therapy, transfusion
    and antimicrobial cover for the neutropenic phase. In a poisoning with no
    antidote and a reversible lesion, keeping the patient alive through the
    cytopenic window is the whole of the treatment.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      there are currently no specific antidotes for colchicine poisoning
    explanation: >-
      Establishes the absence of an antidote, which is why supportive care carries
      the treatment.
  - reference: PMID:7530779
    reference_title: "Colchicine toxicity--clinical features and treatment. Massive overdose case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although anticolchicine monoclonal antibody administration is the only
      specific therapy described, intensive supportive care including granulocyte
      colony-stimulating factor administration can facilitate recovery from severe
      colchicine intoxication.
    explanation: >-
      States that intensive supportive care can carry a patient through severe
      poisoning.
  - reference: PMID:20586571
    reference_title: "Colchicine poisoning: the dark side of an ancient drug."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Although a specific experimental treatment (Fab fragment antibodies) for
      colchicine poisoning has been used, it is not commercially available.
    explanation: >-
      Records that the one specific therapy described is unavailable in practice,
      which is why this entry curates supportive care rather than an antidote.
  - reference: PMID:36028733
    reference_title: "Progress in the management of acute colchicine poisoning in adults."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      its Vd can even reach up to 21 L/kg in overdose
    explanation: >-
      Gives the volume of distribution in overdose. A distribution volume of this
      size is the reason extracorporeal removal is not curated here as a means of
      clearing colchicine.
  notes: >-
    Colchicine-specific Fab fragments are not curated as a treatment of this
    disease because they are not commercially available, per the cited systematic
    review. Extracorporeal removal is likewise not curated as a means of clearing
    the drug: the volume of distribution cited above makes colchicine a poor
    dialysis candidate, and the renal replacement therapy used in the reported
    cases was for the acute kidney injury rather than for drug removal.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Colchicine Poisoning · 2026-09-01T22:53:27Z · View source

New entry for colchicine poisoning (MONDO:0017859), curated as a two-clock toxicology entry: one molecular lesion (colchicine-tubulin binding, which blocks microtubule assembly) branching into a fast mitotic-arrest arm that kills, and a slow transport-failure arm that produces the therapeutic-dose neuromyopathy. Pathograph: 12 pathophysiology nodes, fully connected apart from the CYP3A4/P-glycoprotein clearance node, which is an intentional modifier entry point. Six conforms_to declarations across two modules - the complete myelosuppression chain (cytotoxic insult to progenitors, marrow suppression, multilineage cytopenias, cytopenia-related complications) and two nodes of peripheral_axonal_degeneration (axonal transport impairment, distal axonal degeneration). Both peripheral_axonal_degeneration conformances carry notes recording that they are partial: the module nodes name mitochondrial dysfunction and axonal/demyelinating fibre pathology, and the human sources cited here establish neither. A hepatorenal feedback edge closes a loop back onto the exposure node, since hepatic clearance carries most of the drug's elimination. Evidence: 84 evidence items over 10 references, all fetched with just fetch-reference, and every snippet pre-verified against the local cache before the YAML was written. Anchors are two systematic reviews (PMID:20586571, clinical toxicology review; PMID:36512928, systematic review of 143 neuromyopathy cases), a full-text management review carrying a 20-case series (PMID:36028733), and individual case reports for the marrow and G-CSF claims. Frequency discipline: FREQUENT is asserted only for the three gastrointestinal symptoms, and each explanation names the denominator (14 of 20 published adult case reports) and states that the series skews towards severe poisoning. No band is asserted for any cytopenia or organ-failure phenotype, because publication bias inflates exactly those figures. Claims deliberately not made: no bacterial-translocation claim on the neutropenic sepsis edge (blood cultures were positive in 5 of 20 patients but the route of entry was not established); no mitochondrial claim on the transport arm; Fab fragments and extracorporeal drug removal are recorded in notes as not curated, with the volume-of-distribution figure justifying the latter carried as a cited snippet rather than as bare prose. Deep research: just research-disorder claude_code produced a 95 KB report, 59/59 references resolved, 0 unresolved, 0 off topic. NEC preflight returned SKIP (MONDO records no causal gene for a poisoning) and was cleared manually - CYP3A4 and ABCB1 dominate the report's gene mentions, and those are colchicine's own metabolism and efflux genes. The report was used as leads only; zero snippets were taken from it. It did surface two genuine gaps in the draft, the cardiac branch and the hepatorenal feedback loop, and both were verified independently against papers already in the cache before being added. Validation: just validate-disorders (the batched sweep CI runs) passed; 84/84 snippets verified; check-duplicate-keys, check-folded-hyphens, check-title-snippets, check-entity-refs, check-causal-targets and check-environmental-evidence all clean. Every reference_title was generated programmatically from the cache files, never typed. Review round 1 (ai4c-reviewer, CHANGES_REQUESTED) raised two blocking omissions, both closable from references already cached. Both were correct. A diagnosis: section was added (exposure-history-plus-toxidrome recognition, the separate problem of recognising the chronic neuromyopathy, and MRI for biopsy targeting carrying its source's own hedge), plus a histopathology: entry for the vacuolar myopathy. A second environmental: entry was added for the plant-ingestion route (Colchicum autumnale, Gloriosa superba), bound to ECTO:9000271 exposure to alkaloid rather than ECTO:0000509 exposure to drug. The reviewer's second finding also exposed a hole in this entry's own reasoning: the original ECTO note rejected exposure to alkaloid on the grounds that the poisoning is medicinal, a scoping premise the entry never declared and that the plant route falsifies. That note was rewritten rather than patched around. Following the plant route into the literature added PMID:30888889, a 297-patient Gloriosa superba cohort with a 10 percent case fatality. That figure is a population rate and is explicitly not comparable with the 14 to 26 percent quoted elsewhere in the entry, which comes from published tablet- overdose case reports; the explanation says so. The same paper reports that plant ingestion caused only mild acute kidney injury and rhabdomyolysis, so both of those phenotypes now carry a route-dependence qualifier instead of implying a single severity. Its concentration-versus-outcome finding was also added to the exposure node, which previously rested only on the absence of a dose boundary. Non-blocking items also taken: P-glycoprotein efflux bound to GO:0042908 on the clearance node, the statin-myopathy interaction sentence added, and gastric lavage recorded in the charcoal treatment as a narrow adjunct rather than curated as a separate treatment. Review round 2 (ai4c-reviewer, CHANGES_REQUESTED) found one defect introduced by the round-1 fix: the plant-route notes: still said the sources gave no case-fatality figure for that route and that none was asserted, three lines below the evidence item quoting 10 percent (29/297) from PMID:30888889. The note was written before that paper was pulled in and was never revisited. It now states the figure and marks it as a population rate from one country's self-poisoning presentations rather than a case fatality for plant ingestion generally. The trigger node's "the two routes" phrasing was also updated, since the description now names three. Swept the rest of the entry for the same failure mode - prose that was true when written and falsified by later evidence. Every remaining negative claim about the sources was re-checked against its block, and every phenotype was cross-checked so that no frequency band coexists with an explanation saying none is asserted. None found.

Claude Code ▸
Colchicine Poisoning — Research Report
claude-haiku-4-5-20251001, claude-opus-5 10 citations 2026-09-01T18:46:24.007644

Colchicine Poisoning — Research Report

Prepared: 2026-09-01. Target: Colchicine Poisoning. MONDO: MONDO:0017859 (verified against OLS4; label colchicine poisoning). Category: Complex / toxic exposure disorder.

Scope note. This is a toxic exposure disorder, not a Mendelian disease. Sections 4 and 9 are therefore reframed: there are no causal genes, and the genetic content that exists is host pharmacogenetics governing colchicine disposition. Where a template item does not apply, I say so rather than filling it.

Ontology note. Every CURIE below was resolved against the EBI Ontology Lookup Service (OLS4) on 2026-09-01 and the returned label is the one printed. Four suggested NCI Thesaurus concepts did not resolve by exact label and are flagged as unresolved. A term resolving is not the same as a term being right for the claim; treat these as leads.

1. Disease Information

Colchicine poisoning is systemic multi-organ injury caused by exposure to colchicine, a tricyclic lipid-soluble alkaloid of Colchicum autumnale and Gloriosa superba. It follows deliberate self-poisoning, accidental ingestion of the plant, dosing error, or accumulation when clearance falls. The drug has a narrow therapeutic index and no antidote in routine clinical use.

MONDO's own definition: "A potentially life-threatening condition from ingesting colchicine drug or Colchicum autumnale plant. It begins with gastrointestinal symptoms causing severe dehydration, progresses to marrow failure within 24 hours, and can result in multi-organ failure including renal failure, cardiac arrest, and shock within 1-3 days."

Identifiers

Vocabulary Identifier Note
MONDO MONDO:0017859 verified, label colchicine poisoning
Orphanet ORPHA:31824 from MONDO xrefs
SNOMED CT 24354007 from MONDO xrefs
ICD-9-CM 974.7 from MONDO xrefs
ICD-11 (foundation) 1617857912 from MONDO xrefs
ICD-10-CM T50.4X1A – T50.4X4A (poisoning, by intent); T50.4X5A (adverse effect) "Drugs affecting uric acid metabolism". Crosswalked from ICD-9 974.7. I could not open the ICD-10-CM Table of Drugs page directly (HTTP 403), so the colchicine index entry is inferred, not confirmed.
MeSH D003078 (Colchicine), subheading /poisoning verified via NCBI E-utilities. There is no colchicine-poisoning descriptor; the concept is drug + subheading.
CHEBI (agent) CHEBI:23359 colchicine verified
NCIT (agent) NCIT:C385 Colchicine verified
OMIM not applicable no Mendelian entry; this is an exposure

Synonyms: colchicine toxicity, colchicine intoxication, colchicine overdose, autumn crocus poisoning, meadow saffron poisoning, Colchicum autumnale poisoning, Gloriosa superba poisoning ("niyangala" poisoning, Sri Lanka), colchicine toxicosis (veterinary).

Data provenance. Both. Individual-patient sources dominate the literature (case reports, poison-centre call records, ICU registries). Aggregated disease-level resources contribute the ontology mappings and the national poison-centre denominators. The largest patient-level series are the Sri Lankan Gloriosa cohort (n = 297, PMID:30888889), the Turkish paediatric ICU cohort (n = 150, PMID:42499431), the UK paediatric NPIS series (n = 57, PMID:41663238), the Hong Kong clarithromycin co-prescription study (n = 116, PMID:16007523), and a Chinese acute-poisoning series (n = 43, PMID:34484680).

2. Etiology

Causal factor

One molecule. Colchicine binds tubulin and blocks microtubule assembly. Everything downstream is that lesion propagating through tissues ranked by how much they need microtubules.

Finkelstein et al. state it plainly (PMID:20586571): "Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network."

Routes of exposure:

  1. Deliberate self-poisoning with tablets or with plant material. In the Sri Lankan series, Gloriosa superba self-poisoning was the dominant presentation (PMID:30888889).
  2. Accidental plant ingestion. Colchicum autumnale leaves mistaken for wild garlic (Allium ursinum) — a documented and recurrent European error (PMID:42043136). Gloriosa superba tubers mistaken for ginger (PMID:41628608).
  3. Therapeutic dosing error, including iatrogenic tenfold overdose (PMID:33898365, a 4-year-old given 0.5 mg/kg).
  4. Accumulation at therapeutic dose when renal or hepatic clearance falls, or a CYP3A4/P-glycoprotein inhibitor is co-prescribed. This is the commonest fatal mechanism in older patients and produces the chronic neuromyopathic phenotype rather than the acute one.

Risk factors — environmental and clinical

Factor Evidence Source
Ingested dose > 0.5 mg/kg "High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg." PMID:20586571
Dose ≥ 0.8 mg/kg Survival 28.60% in that band, vs 83.33% at 0.5–0.8 mg/kg and 100% at ≤ 0.5 mg/kg (n = 43) PMID:34484680
Renal impairment Independent predictor of death with clarithromycin co-therapy (RR 9.1; 95% CI 1.75–47.06; P < 0.001) PMID:16007523
Hepatic impairment Blocks the primary elimination route; the plateau in a poisoned child's blood level was attributed to liver failure PMID:33898365
CYP3A4 + P-gp inhibitor co-prescription 9/88 (10.2%) died on concomitant clarithromycin vs 1/28 (3.6%) sequential PMID:16007523
Any CYP3A4/P-gp inhibitor (FAERS signal) 37 reporting-odds-ratio and 34 observed/expected safety signals; strongest ROR colchicine + atazanavir with rhabdomyolysis/myopathy, ROR 35.4 (95% CI 12.8–97.6) PMID:36688283
Statin co-therapy Statin use was a significant covariate on colchicine clearance in a population PK model; risk concentrated in low-body-weight patients PMID:40719983
Older age Median colchicine concentration 4.7 ng/mL (IQR 1.7–6.6) in those over 65 vs 1.2 (IQR 0.2–2.7) under 35 PMID:30888889
Low body weight Body weight was a significant predictor of colchicine PK PMID:40719983
Delayed presentation "Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis." PMID:20586571
Polypharmacy, advanced age Named risk group in the 2026 review PMID:42618164
Long duration of therapy 48% of neuromyopathy cases had taken colchicine > 12 months before presenting PMID:36512928

Named interacting drugs (PMID:20586571): "CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy." CHEBI leads: clarithromycin CHEBI:3732 (verified), atorvastatin CHEBI:39548 (verified).

Genetic risk factors

There is no disease-causing genotype. There is a transporter genotype that modulates exposure.

  • ABCB1 (HGNC:40, P-glycoprotein) is the efflux transporter that limits colchicine absorption and drives biliary/renal efflux. A 2025 systematic review concluded that "P-glycoprotein is considered a key transporter protein as it regulates the absorption, distribution, and excretion of several drugs, including colchicine. In diseases like FMF, ABCB1 polymorphisms have been shown to affect the response to colchicine, potentially leading to treatment resistance or altered toxicity" (PMID:40136464).
  • A two-case series with muscle transcript data reported "the descriptive finding of reduced ABCB1 transcript levels in the colchicine myopathy patients" (PMID:31178824). Both cases were on rosuvastatin. That is descriptive, n = 2, and hypothesis-generating.
  • CYP3A4 (HGNC:2637) and CYP3A5 (HGNC:2638) are the metabolic route. I found no adequately powered study linking a CYP3A5 expressor genotype to colchicine toxicity risk. Stated as absence of evidence, not evidence of absence.

Assessment. No validated pharmacogenetic test guides colchicine dosing today. CPIC has no colchicine guideline that I located. The tractable genetic risk story is ABCB1 expression, and it is not yet actionable.

Protective factors

  • Genetic: none identified.
  • Environmental / clinical: early presentation and early gastrointestinal decontamination. Recovery followed presentation one hour after a 1.38 mg/kg ingestion, against a fatal outcome at 0.39–0.65 mg/kg presenting at 44 hours (both discussed in PMID:34229452). Dose reduction in renal or hepatic impairment. Avoiding CYP3A4/P-gp inhibitor co-prescription outright: "these 2 drugs should not be coprescribed, because of the risk of fatality" (PMID:16007523).
  • Restarting colchicine at reduced dose after neuromyopathy was usually tolerated — 73% had no symptom recurrence in 15 rechallenged cases (PMID:36512928).

Gene–environment interaction

The interaction is pharmacokinetic and it is the core of the disease. A patient with reduced ABCB1 function, or a CYP3A4 inhibitor on board, or a failing kidney, converts a therapeutic dose into a toxic exposure without any change in what was swallowed. The Hong Kong data quantify one arm of it (PMID:16007523). The FAERS disproportionality analysis maps the drug space (PMID:36688283). The genotype arm is characterised but not quantified (PMID:40136464).

3. Phenotypes

Colchicine poisoning runs in three overlapping phases. Finkelstein et al. define them (PMID:20586571): "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 ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis."

Phase 1 — gastrointestinal (0–24 h)

Phenotype HPO suggestion (verified label) Frequency / note
Nausea and vomiting HP:0002018 Nausea; HP:0002013 Vomiting 64.7% of 150 paediatric cases (PMID:42499431)
Abdominal pain HP:0002027 Abdominal pain 36.7% (PMID:42499431)
Diarrhea HP:0002014 Diarrhea 24% paediatric (PMID:42499431); universal in experimentally poisoned calves (PMID:9764409)
Leukocytosis HP:0001974 Leukocytosis Early, and a diagnostic trap — it reads as sepsis
Hypotension / hypovolaemic shock HP:0002615 Hypotension From fluid and electrolyte loss
Lactic acidosis HP:0003128 Lactic acidosis Part of the named toxidrome

The toxidrome to recognise (PMID:20586571): "Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia)."

Severity/progression: acute onset, self-limited in mild exposure, or the opening of a fatal course. Around half of UK paediatric cases were symptomatic at presentation, gastrointestinal upset in 39% (PMID:41663238). Asymptomatic presentation does not exclude later systemic toxicity — the UK authors state exactly that.

Phase 2 — multi-organ dysfunction (24 h – 7 days)

Phenotype HPO suggestion Frequency / note
Pancytopenia HP:0001876 Pancytopenia The defining haematological lesion
Neutropenia HP:0001875 Neutropenia Grade 4 reported (PMID:36319015)
Thrombocytopenia HP:0001873 Thrombocytopenia Nadir 13 × 10⁹/L in one ECLS survivor (PMID:26230148)
Anemia HP:0001903 Anemia Grade 2 upward (PMID:36319015)
Bone marrow hypocellularity HP:0005528 Bone marrow hypocellularity Structural correlate
Disseminated intravascular coagulation HP:0005521 Disseminated intravascular coagulation Coagulation system most frequently affected in paediatric MODS, 26% (PMID:42499431)
Acute kidney injury HP:0001919 Acute kidney injury Only mild AKI after Gloriosa ingestion (PMID:30888889); severe and dialysis-refractory in tablet overdose (PMID:34229452)
Elevated hepatic transaminase HP:0002910 Elevated hepatic transaminase AST an independent MODS predictor (PMID:42499431)
Hepatic failure HP:0001399 Hepatic failure Centrilobular necrosis at autopsy (PMID:37222938)
Rhabdomyolysis HP:0003201 Rhabdomyolysis Mild after Gloriosa; marked in tablet overdose
Elevated creatine kinase HP:0003236 Elevated circulating creatine kinase activity Kuncl: "always presents with elevation of serum creatine kinase" (PMID:3035372)
Cardiac arrhythmia HP:0011675 Arrhythmia Second-degree AV block documented in a poisoned dog (PMID:31883205)
Cardiac arrest HP:0001695 Cardiac arrest A leading terminal event
Respiratory distress / hypoxemia HP:0002098 Respiratory distress; HP:0012418 Hypoxemia ARDS reported (PMID:9786547)
Hypocalcemia HP:0002901 Hypocalcemia (PMID:9786547, PMID:34229452)
Hyponatremia HP:0002902 Hyponatremia Including SIADH after Gloriosa
Hypoglycemia HP:0001943 Hypoglycemia Refractory in one fatal case (PMID:34229452)
Seizure HP:0001250 Seizure With encephalopathy from cerebral oedema
Sepsis HP:0100806 Sepsis Death route via neutropenia; Candida dubliniensis isolated post mortem in one case (PMID:34229452)

Cardiovascular collapse, not marrow failure, is the usual proximate cause of death in acute oral poisoning — a claim carried in the Cozza review and worth flagging as a review-level statement rather than a primary result. The Chinese series is the primary support: "The causes of death were cardiovascular and bone marrow hematopoietic failures" (PMID:34484680).

Phase 3 — recovery (7–21 days)

Phenotype HPO suggestion Note
Rebound leukocytosis HP:0001974 Leukocytosis Marrow escape
Alopecia HP:0001596 Alopecia Days 5–16 post ingestion; historically documented as alopecia totalis after suicidal overdose (PMID:14164521)

Finkelstein: "Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness" (PMID:20586571).

Chronic / therapeutic-dose phenotype: colchicine neuromyopathy

A separate clock, a separate presentation, and misdiagnosed more often than not. Kuncl's 1987 description remains canonical (PMID:3035372): "It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly." And: "colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy."

Phenotype HPO suggestion Frequency
Proximal muscle weakness HP:0003701 Proximal muscle weakness Predominant symptom in 143 reviewed cases (PMID:36512928)
Myopathy (vacuolar) HP:0003198 Myopathy Lysosome/autophagic-vacuole accumulation (PMID:3035372); imaged and re-reported 2019–2025 (PMID:31819001, PMID:39870408)
Peripheral axonal neuropathy HP:0003477 Peripheral axonal neuropathy Combined neuropathy + myopathy in 72/143 (51%) (PMID:36512928)

Mean total daily dose in the neuromyopathy series was 1.25 ± 0.60 mg — ordinary therapeutic dosing (PMID:36512928). 117/143 (82%) had a significant comorbidity or a probable drug–drug interaction; 57 (40%) had both. Cessation gave complete resolution in 70% of cases at a median of 21 days.

Quality of life

I found no colchicine-poisoning-specific EQ-5D, SF-36, or PROMIS data. Stated as a gap. Functional impact is inferable per phenotype: neuromyopathy causes reversible proximal weakness with a median 21-day resolution (PMID:36512928); acute survivors of the multi-organ phase carry ICU-course morbidity (dialysis, ventilation, transfusion burden — 15 red-cell, 13 platelet, and 7 plasma units in one survivor, PMID:26230148); alopecia is cosmetic and reversible.

4. Genetic / Molecular Information

Causal genes: none. This is an exposure disorder. There is no pathogenic variant, no variant classification, no allele frequency, no somatic/germline distinction, no chromosomal abnormality, and no epigenetic disease mechanism to report. Any KB entry should record these as not applicable rather than empty.

What genetics does contribute:

Host disposition genes.

Gene HGNC (verified) Role
ABCB1 HGNC:40 P-glycoprotein efflux; polymorphism alters colchicine exposure and toxicity risk (PMID:40136464, PMID:31178824)
CYP3A4 HGNC:2637 Principal oxidative metabolism (PMID:29359661)
CYP3A5 HGNC:2638 Same subfamily; no colchicine-specific toxicity association found

Drug target genes. Colchicine's target is the αβ-tubulin heterodimer. Representative human genes: TUBA1A HGNC:20766, TUBB HGNC:20778. Note this is a drug target, not a disease gene — the binding site is intact wild-type tubulin, and that is precisely why the poisoning is universal rather than genotype-restricted.

Therapy-relevant gene. CSF3 HGNC:2438 (colony stimulating factor 3) is the gene product administered as filgrastim in the rescue of the marrow phase.

Chromosomal effects — a genuine molecular finding, and a real one. Colchicine is a spindle poison, so it produces aneugenic effects. Chromosomal aberrations have been tracked serially alongside marrow suppression in acute human poisoning (PMID:35237367; title and journal confirmed, abstract not indexed in PubMed, so I have not read the numbers). This is a downstream consequence of the exposure, not an inherited abnormality.

Epigenetics: no colchicine-poisoning methylation or chromatin dataset located in ENCODE, Roadmap, or the literature search. Gap.

5. Environmental Information

The exposure is the disease. Suggested ECTO-style framing: exposure to colchicine via ingestion; exposure to Colchicum autumnale plant material via ingestion; exposure to Gloriosa superba tuber via ingestion. I did not resolve ECTO CURIEs for these and will not guess them — the correct move is an ECTO search at curation time, and recording the absence in notes if nothing fits.

Plant sources. Colchicum autumnale (autumn crocus, meadow saffron) and Gloriosa superba (glory lily, "niyangala"). The 2018 pharmacology review calls colchicine "a tricyclic, lipid-soluble alkaloid derived from the plant of the Lily family Colchicum autumnale, sometimes called the 'autumn crocus'" (PMID:29359661). Cattle poisoning material additionally contained demecolcine alongside colchicine (PMID:9764409).

Occupational / agricultural. Livestock exposure from mown meadow forage. A Swiss organic dairy herd showed apathy, hypothermia, and reduced milk yield after eating cut forage containing autumn crocus leaves, and bulk milk tested positive for colchicine by LC-MS/MS two weeks after the event, negative at five weeks (PMID:40905265). That makes colchicine a food-chain hazard as well as a clinical one.

Lifestyle factors. Grapefruit juice is a named CYP3A4 inhibitor raising colchicine concentration (PMID:20586571). Alcohol appears in chronic-toxicity case narratives as a comorbid factor (PMID:35047617). Foraging for wild garlic is the specific behaviour behind European accidental plant poisoning (PMID:42043136).

Infectious agents. None cause this disease. Infection enters as a consequence: neutropenic sepsis is a death route (PMID:20586571, PMID:34229452). There is a second, inverse relationship worth noting — colchicine is being studied against NLRP3-driven inflammation in COVID-19 and influenza, which puts more colchicine into more hands and widens the exposed population (PMID:42589484).

6. Mechanism / Pathophysiology

Ordered causal chain

  1. Colchicine is absorbed from the gut and enters cells. It is lipid-soluble and distributes widely, with an apparent volume of distribution of 4.87 ± 2.05 L/kg in patients with normal renal function (PMID:8035398). Absorption and efflux are gated by P-glycoprotein; metabolism is hepatic via CYP3A4 (PMID:29359661). Leads to an intracellular colchicine burden, highest in myeloid cells, which preferentially accumulate the drug (PMID:42589484).
  2. Intracellular colchicine binds the αβ-tubulin heterodimer at the colchicine site. Ravelli et al. determined the structure at 3.5 Å and state the mechanism: "the tubulin-colchicine complex sheds light on the mechanism of colchicine's activity: we show that colchicine binds at a location where it prevents curved tubulin from adopting a straight structure, which inhibits assembly" (PMID:15014504). GO leads: GO:0015631 tubulin binding, GO:0008017 microtubule binding. Leads to step 3.
  3. Tubulin is locked in the curved conformation and cannot polymerise. Loss of lateral contacts between protofilaments follows. Leads to net microtubule depolymerisation. GO: GO:0046785 microtubule polymerization (blocked), GO:0007017 microtubule-based process, GO:0005874 microtubule (cellular component).
  4. The microtubule network collapses in every cell that has taken up drug. The consequence list is enumerated by Finkelstein et al. (PMID:20586571): "affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility." GO: GO:0006887 exocytosis, GO:0006897 endocytosis, GO:0008088 axo-dendritic transport, GO:0005819 spindle. The chain branches here. Four branches follow, on different clocks.

Branch A — mitotic arrest in rapidly dividing tissue (hours to days; the lethal branch).

5a. Spindle assembly fails in cells attempting mitosis. GO: GO:0007052 mitotic spindle organization, GO:0000278 mitotic cell cycle, GO:0051301 cell division. Leads to metaphase arrest. 6a. Arrested cells die by apoptosis. This is directly demonstrated, not inferred. Experimental Colchicum poisoning in cattle showed "cellular injury caused by autumn crocus was closely associated with apoptosis" by in-situ DNA strand-break analysis and electron microscopy (PMID:10458107, MODEL_ORGANISM). In mice, colchicine raised duodenal crypt apoptotic indices with the highest values in the deepest crypt regions (PMID:15865323, MODEL_ORGANISM). GO: GO:0006915 apoptotic process. 7a. Gut arm: intestinal crypt enterocytes (CL:0000584 enterocyte) die, the mucosal barrier is lost, and secretory diarrhoea with massive fluid and electrolyte loss follows. Calf histology confirms the target: "necrosis and degeneration with karyopyknosis and karyorrhexis were shown in the basal cell layer of the tongue, esophagus, forestomach, renal pelvis, urinary bladder, neck cell layer of the abomasal gastric glands, and intestinal cryps" (PMID:9764409). Leads to hypovolaemia, hypotension, lactic acidosis, prerenal azotemia — phase 1. 8a. Marrow arm: haematopoietic progenitors (CL:0000037 hematopoietic stem cell, CL:0000763 myeloid cell, CL:0000556 megakaryocyte) arrest and die in UBERON:0002371 bone marrow. Leads to pancytopenia at 24 h to 7 days, with neutropenia the dangerous component. Leads to neutropenic sepsis and bleeding.

Branch B — cardiac (hours to days; the usual proximate cause of death in acute overdose).

5b. Microtubule disruption interferes with cardiac myocyte (CL:0000746 cardiac muscle cell) conduction and contractility (PMID:20586571). A 2024 case report puts it as "Direct cellular toxicity interferes with myocardial contractility, leading to cardiovascular collapse" (PMID:39484332). Leads to arrhythmia, reduced ejection fraction, refractory cardiogenic shock. Ejection fraction fell to 5–10% in one survivor before extracorporeal support (PMID:26230148). Leads to cardiac arrest.

Branch C — neuromuscular (weeks to years; the therapeutic-dose branch).

5c. Microtubule-dependent intracellular transport fails in muscle and in long axons (CL:0000540 neuron; UBERON:0001630 muscle organ; UBERON:0001021 nerve). Kuncl inferred the mechanism from morphology: "The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes" (PMID:3035372). GO: GO:0005764 lysosome, GO:0006914 autophagy. This step is explicitly inferred, not demonstrated. 6c. Lysosomes and autophagic vacuoles accumulate. Leads to vacuolar myopathy with proximal weakness and elevated creatine kinase, plus a slower axonal polyneuropathy. Reversible on withdrawal.

Branch D — hepatic, renal, and the feedback loop.

5d. Hepatocyte (CL:0000182 hepatocyte, UBERON:0002107 liver) injury and renal tubular injury (UBERON:0002113 kidney) occur, with centrilobular hepatic necrosis at autopsy (PMID:37222938). 6d. This closes a positive feedback loop. Colchicine's principal elimination is hepatic with enterohepatic recirculation and 10–30% renal (PMID:33898365). Damaging both organs slows clearance of the poison damaging them. Cozza et al. make the point directly: "With our patient having both liver and kidneys impairment, this could have led to his progression of MOF" (PMID:34229452). Toxicokinetic confirmation: blood colchicine plateaued for six days in a poisoned child, "indicating impeded elimination resulting from liver failure" (PMID:33898365).

  1. Convergence: hypovolaemia, cardiogenic shock, pancytopenia, coagulopathy, and impaired clearance converge on multi-organ dysfunction syndrome and death. Recovery, when it comes, follows the reverse order of organ involvement — "the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver" (PMID:34484680).

The therapeutic mechanism is the same lesion, dialled down

At therapeutic dose the same tubulin binding produces the anti-inflammatory effect: "Colchicine interferes with several inflammatory pathways including adhesion and recruitment of neutrophils, superoxide production, inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway attenuating the inflammatory response" (PMID:29359661). GO leads: GO:0030595 leukocyte chemotaxis, GO:0072559 NLRP3 inflammasome complex. There is no separate toxic mechanism to find. The therapeutic window is quantitative, which is exactly why it is narrow.

Multi-omics

  • Transcriptomics: the only disease-relevant human transcript measurement I found is reduced ABCB1 transcript in muscle from two colchicine-myopathy patients (PMID:31178824). No GEO series specific to colchicine poisoning was located.
  • Proteomics / metabolomics / lipidomics / single-cell / spatial: none located for this disorder. Gaps.
  • Biomarker panel work (the closest thing to omics here): the Sri Lankan study measured serum creatinine, cystatin C, creatine kinase, and urinary KIM-1, clusterin, albumin, β2-microglobulin, cystatin C, NGAL, osteopontin, and trefoil factor 3 in 45 patients, and concluded "Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and rhabdomyolysis" (PMID:30888889).
  • Functional genomics screens: none specific to colchicine poisoning. Colchicine is widely used as a reagent in cell-biology screens, which is a different claim and should not be curated as disease evidence.

7. Anatomical Structures Affected

Primary targets — highest mitotic index and highest drug uptake.

Structure UBERON (verified) Injury
Bone marrow UBERON:0002371 Progenitor arrest, hypocellularity, pancytopenia
Intestine UBERON:0000160 Crypt enterocyte apoptosis, mucosal barrier loss
Colon UBERON:0001155 Secretory diarrhoea
Hair follicle UBERON:0002073 Anagen arrest → alopecia days 5–16

Secondary / systemic involvement.

Structure UBERON Injury
Heart UBERON:0000948 Contractility and conduction failure; septal microinfarct at autopsy (PMID:37222938)
Liver UBERON:0002107 Transaminitis, centrilobular necrosis, acute liver failure
Kidney UBERON:0002113 AKI, tubular injury; renal-pelvis epithelial necrosis in calves (PMID:9764409)
Muscle organ UBERON:0001630 Vacuolar myopathy, rhabdomyolysis
Nerve UBERON:0001021 Axonal polyneuropathy
Lung UBERON:0002048 ARDS, respiratory failure

Body systems: digestive, haematopoietic and immune, cardiovascular, renal, hepatobiliary, neuromuscular, respiratory, integumentary.

Cell populations (Cell Ontology, verified).

Cell type CL Role
enterocyte CL:0000584 crypt apoptosis, phase 1
hematopoietic stem cell CL:0000037 progenitor arrest
myeloid cell CL:0000763 preferential drug accumulation (PMID:42589484)
neutrophil CL:0000775 chemotaxis inhibition; necrobiosis reported (PMID:42053158)
megakaryocyte CL:0000556 thrombocytopenia
cardiac muscle cell CL:0000746 contractility/conduction failure
hepatocyte CL:0000182 centrilobular necrosis
neuron CL:0000540 axonal transport failure

Also implicated in the cattle model: Kupffer cells, renal tubular epithelial cells, and lymphocytes (PMID:9764409).

Subcellular (GO cellular component, verified): GO:0005874 microtubule, GO:0005819 spindle, GO:0005764 lysosome, GO:0072559 NLRP3 inflammasome complex.

Lateralization: not applicable. The distribution is systemic and symmetric. Neuromyopathy is bilateral and proximal.

8. Temporal Development

Onset. Any age. Acute in overdose, insidious in accumulation. The two clocks are the disease's defining structural feature.

  • Acute overdose: gastrointestinal onset at 10–24 h (PMID:20586571), sometimes earlier. Peak serum concentration at 0.5–3.0 h post ingestion (PMID:34229452).
  • Chronic accumulation: 48% of neuromyopathy cases had been on colchicine more than 12 months (PMID:36512928). One reported case had taken it for 23 years before presenting with neuromyopathy, gastric ulcers, and myelosuppression (PMID:35047617).

Stages.

Phase Window Content
1 — Gastrointestinal 0–24 h Vomiting, diarrhoea, abdominal pain, leukocytosis, hypovolaemia, lactic acidosis
2 — Multi-organ dysfunction 24 h – 7 days Shock, arrhythmia, AKI, liver failure, pancytopenia, DIC, rhabdomyolysis, encephalopathy, seizures. Death occurs here.
3 — Recovery 7–21 days Organ recovery, rebound leukocytosis, alopecia

Progression rate. Rapid. Deaths in the reported series occur on hospital days 7–8 (PMID:34229452, PMID:9786547, PMID:37222938). Experimental calves died within 63 hours (PMID:9764409). A poisoned dog was euthanised at ~24 hours (PMID:14992256). Minipigs given 0.25 mg/kg IV required euthanasia at a mean 22.5 h (SD 3.2) (PMID:29334816).

Course pattern. Acute, monophasic, self-limited if survived. Not relapsing. Not chronic — with the exception of the chronic-accumulation neuromyopathy, which is progressive while the drug continues and remits on withdrawal.

Duration. Acute illness resolves over days to a few weeks. Neuromyopathy resolves at a median of 21 days after cessation (PMID:36512928).

Remission. Treatment-facilitated and spontaneous. There is no antidote to induce it; withdrawal plus supportive care is the mechanism.

Critical periods — the intervention windows.

  • < 60 min: gastric lavage may be warranted for very large recent ingestions (PMID:20586571).
  • First hours: early activated charcoal. Presentation at 1 hour was associated with recovery from 1.38 mg/kg; presentation at 44 hours with death at a lower dose (PMID:34229452).
  • 1–3 hours (experimental): Fab given 1 or 3 h after colchicine gave survival to study end without marked cardiotoxicity; the same dose at 6 h did not prevent toxicity (PMID:29334816). That is the sharpest therapeutic-window result in the field.

9. Population and Epidemiology

Inheritance: not applicable. There is no inheritance pattern, penetrance, expressivity, anticipation, germline mosaicism, founder effect, consanguinity role, or carrier frequency, because this is an exposure disorder. Record as not applicable.

Incidence and case fatality

Population Measure Value Source
UK children < 18 Minimum incidence 0.41 cases/million children/year (57 cases over 2011–2021) PMID:41663238
UK children Case fatality 4/57 (7%); MOF in 7/57 (12%); systemic toxicity 12/57 (21.1%) PMID:41663238
Sri Lanka, Gloriosa superba self-poisoning Case fatality 10% (29/297) PMID:30888889
Türkiye, paediatric ICU MODS rate 26.7% of 150; single-organ failure 7.3%; no organ failure 66% PMID:42499431
China, acute colchicine poisoning Survival by dose 100% (≤0.5 mg/kg), 83.33% (0.5–0.8), 28.60% (≥0.8) PMID:34484680
Hong Kong, clarithromycin co-prescription Mortality 10.2% concomitant vs 3.6% sequential PMID:16007523
FAERS reports with colchicine + CYP3A4/P-gp inhibitor + AE Severity 61% hospitalisation, 24% death among reports stating severity (n = 787) PMID:36688283

Prevalence: not a meaningful measure for an acute poisoning. Use incidence and case fatality.

Geographic distribution. Two distinct epidemiologies.

  • Pharmaceutical overdose: wherever colchicine is prescribed. Expanding, because indications are expanding — gout and familial Mediterranean fever have been joined by pericarditis, coronary artery disease, and cardiovascular event prevention (PMID:42618164, PMID:41663238).
  • Plant poisoning: Gloriosa superba in South Asia, notably Sri Lanka, where it accounts for a large share of plant poisonings; Colchicum autumnale in Europe, both as foraging error and as livestock/pasture exposure (Switzerland, Germany, Italy, Croatia).

Age distribution. Bimodal in paediatrics: 40% under 5 years (accidental) and 52% over 13 years (deliberate), in the Turkish cohort (PMID:42499431). UK median age 7 years, range 0–17 (PMID:41663238). Adult self-poisoning cases cluster in young adults; accumulation toxicity clusters in the elderly. Age is a strong mortality signal — "Fatal outcomes and high concentrations were both much more common in the elderly" (PMID:30888889).

Sex ratio. No reliable sex ratio located for colchicine poisoning specifically. Sex was a significant covariate in colchicine population pharmacokinetics (PMID:40719983), which is a disposition finding, not an incidence one. Gap.

Affected populations. No ethnic predisposition established. Ethnicity was tested as a covariate in the population PK model and was not among the significant predictors (PMID:40719983). Familial Mediterranean fever populations carry elevated exposure by virtue of lifelong therapy, not by susceptibility.

10. Diagnostics

The diagnosis is clinical and historical. No routine assay confirms it in time to matter. One 2023 case notes plainly: "Unfortunately, specific tests of colchicine toxicity were not routinely available" (PMID:37813551).

Establishing the diagnosis

Finkelstein et al. (PMID:20586571): "History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis."

The differential trap is sepsis. A patient with vomiting, diarrhoea, leukocytosis, hypotension, and lactate looks septic, and a 2023 case report exists specifically because the toxicity mimicked septic shock (PMID:37813551).

Laboratory tests

  • Full blood count with differential, serially. Watches for the phase-2 nadir and the phase-3 rebound. This is the single most informative repeated test.
  • Creatine kinase — always elevated in colchicine myopathy (PMID:3035372).
  • Renal panel, liver panel, lactate, coagulation screen (PT/INR, fibrinogen, D-dimer), electrolytes including calcium, magnesium, phosphate, sodium, potassium, glucose. Calcium, magnesium, potassium, phosphate, and glucose derangements are all documented (PMID:34229452).
  • Plasma colchicine concentration — the best prognostic test, and the least available. Assayed by HPLC or LC-MS/MS in research settings.

Biomarkers

The strongest quantitative result in the field is prognostic, not diagnostic (PMID:30888889): "The area under the receiver operating characteristic curve (AUC-ROC) for uncorrected admission colchicine level was highly predictive of a fatal outcome, and this improved even further with two methods we developed to correct for the expected change with time. The best method had an AUC-ROC of 0.98 (95%CI 0.94-1.00) in predicting death, with 100% sensitivity and 96% specificity at the best cut-point."

Reference concentration context: the nominal therapeutic range is 0.5–3 ng/mL (PMID:40719983). Fatal cases in the Sri Lankan cohort had admission medians of 7.8 ng/mL (IQR 5.8–18.7) against 1.2 (0–2.3) in survivors. LOINC codes exist for the routine chemistry and haematology panels; I did not resolve a LOINC code for a plasma colchicine assay and will not invent one.

Imaging and functional studies

  • Echocardiography — detects the reduced ejection fraction that defines the cardiogenic-shock phase (PMID:34229452, PMID:26230148).
  • ECG — arrhythmia and conduction block surveillance.
  • Muscle MRI — described in colchicine myopathy; the first published muscle-MRI data appeared in 2019 (PMID:31178824).
  • Electromyography — "Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity" (PMID:3035372). Nerve conduction studies show the axonal polyneuropathy.
  • CT abdomen/pelvis and chest X-ray were unremarkable in one severe case (PMID:34229452), so normal imaging does not reassure.

Biopsy and pathology

  • Muscle biopsy: vacuolar myopathy. Kuncl: "The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles" (PMID:3035372).
  • Bone marrow: hypocellularity; massive neutrophil necrobiosis has been reported (PMID:42053158, title-level).
  • Autopsy: centrilobular hepatic necrosis and cardiac septal microinfarct (PMID:37222938). Post-mortem bile assay is informative for toxicokinetics — 27 ng/mL in that case.
  • Post-mortem muscle biochemistry is being developed forensically in rats (PMID:41547239).

Genetic testing

Not indicated for diagnosis. WGS, WES, gene panels, single-gene testing, chromosomal microarray, karyotype, FISH, mtDNA testing, and repeat-expansion testing all have no diagnostic role here. ABCB1 genotyping is a research tool for susceptibility (PMID:31178824, PMID:40136464), not a clinical test.

Screening

No population screening exists, and none is indicated. The preventable pathway is prescription screening — automated interaction checking for CYP3A4/P-gp inhibitors and dose review against renal function.

Differential diagnosis

Condition Distinguishing feature
Septic shock Colchicine gives early leukocytosis then profound neutropenia; sepsis rarely inverts that way at 24–72 h. Exposure history decides it. (PMID:37813551)
Acute gastroenteritis Colchicine progresses to marrow failure and cardiogenic shock; gastroenteritis does not
Other cytotoxic/antimitotic overdose Requires exposure history
Polymyositis Kuncl: colchicine myoneuropathy "is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy" (PMID:3035372). CK rises in both; the vacuolar biopsy and the remission on withdrawal separate them
Uraemic neuropathy Same paper, same trap. Renal impairment coexists, which is what makes it hard
Arsenic or thallium poisoning Both give GI phase then alopecia. Toxicological assay separates them

11. Outcome and Prognosis

Mortality

There is no single case-fatality rate. It depends on dose, timing, age, and organ reserve. Reported figures span 7% to 10% in unselected poison-centre and plant-ingestion populations, and rise steeply with dose (see the epidemiology table in section 9).

The dose–prognosis rule, and its erosion. The classical rule attributed to Bismuth and colleagues holds that ingestion below 0.5 mg/kg predicts survival and above 0.8 mg/kg predicts death. It is repeated in nearly every review. I could not retrieve the primary Bismuth publication in this search and flag that as an unverified secondary attribution.

Three recent findings contradict the rule's hard edges:

  1. Survival was 28.6%, not 0%, in the ≥0.8 mg/kg band (n = 43) (PMID:34484680).
  2. Paediatric national-cohort data state directly: "MODS can develop at ingestion doses lower than 0.5 mg/kg, which have historically been considered safe" (PMID:42499431).
  3. UK paediatric fatalities occurred across 0.21 to 1.45 mg/kg, all mixed overdoses (PMID:41663238).

And a fourth, arguing the opposite direction (PMID:42589484): "The widely accepted belief that total doses of 7-7.5 mg are inherently lethal appears to reflect historical cases complicated by drug interactions and/or hepatic or renal impairment, rather than toxicity attributable to colchicine dose alone."

The rule was a plank laid across a stream, and the stream has moved.

Prognostic factors

Factor Direction Source
Admission plasma colchicine concentration Strongest single predictor; AUC-ROC 0.98 with time correction PMID:30888889
Ingested dose per kg Independent MODS predictor in children PMID:42499431
Baseline PRISM III score Independent MODS predictor PMID:42499431
Admission sodium, creatinine, AST Independent MODS predictors PMID:42499431
Age > 65 Higher concentrations, higher fatality PMID:30888889
Delayed presentation Poor prognosis PMID:20586571
Pre-existing renal or hepatic impairment Poor prognosis PMID:20586571, PMID:16007523
Development of pancytopenia RR 23.4 (95% CI 4.48–122.7; P < 0.001) for death in the clarithromycin cohort PMID:16007523
Longer overlapped interacting-drug therapy RR 2.16 (95% CI 1.41–3.31; P ≤ 0.01) PMID:16007523

A 2026 prediction tool exists and is not ready. A bicentre French–Italian nomogram using admission colchicine concentration and time since ingestion was developed on 52 patients and validated on three small cohorts (n = 25, 13, 16). The authors' own conclusion is the correct framing: "An exploratory nomogram for early risk stratification of mortality after colchicine poisoning is presented. Clinical implementation requires prospective multicenter validation with adequate statistical power" (PMID:42522392). Do not curate this as a validated instrument.

Recovery and morbidity

Survivors generally recover completely: "Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness" (PMID:20586571). Neuromyopathy resolved completely in 70% of cases at a median of 21 days after cessation (PMID:36512928).

Complications during the course: neutropenic sepsis (fungaemia documented, PMID:34229452), DIC with diffuse bleeding, dialysis-requiring AKI, ARDS, cardiac arrest, cerebral oedema with seizures, and the iatrogenic burden of ECMO and massive transfusion.

Life expectancy: unaffected in survivors. No long-term excess-mortality cohort located. Gap.

Quality-of-life instruments: none reported for this disorder. Gap.

12. Treatment

There is no antidote in clinical use. Every guideline statement reduces to decontaminate early, support aggressively, and rescue the marrow. Cozza et al.: "There is currently no antidote or directed therapy available for colchicine overdose" (PMID:34229452).

Decontamination

Intervention Evidence NCIT suggestion
Activated charcoal, including multiple-dose "Timely gastrointestinal decontamination should be considered with activated charcoal" (PMID:20586571). Rationale is enterohepatic recirculation. NCIT:C77524 Activated Charcoal (verified; this is the agent, not the action)
Gastric lavage "very large, recent (<60 min) ingestions may warrant gastric lavage" (PMID:20586571) No NCIT term resolved by exact label. Flag for curation.

A caveat that matters. The theoretical case for multiple-dose charcoal targeting enterohepatic recirculation is weaker than it looks. From the fatal adolescent case with a measured post-mortem bile concentration (PMID:37222938): "Assuming that activated charcoal would be able to adsorb 100% of biliary colchicine, using the bile concentration obtained above, only 0.0162mg of colchicine per day would be able to be adsorbed and eliminated by activated charcoal in this patient." Independently, no measurable clearance from charcoal was observed in a monitored paediatric case (PMID:33898365).

Supportive care — the mainstay

Intervention Role NCIT suggestion
Aggressive fluid and electrolyte replacement Phase-1 hypovolaemia NCIT:C116537 Fluid Therapy (verified)
Vasopressors Refractory shock; three agents plus stress-dose steroids in one case (PMID:34229452) No exact-label NCIT term resolved for "Vasopressor Agent". Flag.
Mechanical ventilation Respiratory failure NCIT:C70909 Mechanical Ventilation (verified)
Blood product support DIC, thrombocytopenia; 15 RBC + 13 platelet + 7 FFP units in one survivor (PMID:26230148) NCIT:C15192 Blood Transfusion; NCIT:C15366 Platelet Transfusion; NCIT:C89783 Fresh Frozen Plasma (all verified)
General supportive care Framing term NCIT:C15747 Supportive Care (verified)

Marrow rescue — G-CSF

The best-supported specific intervention. Two early case reports established it: pancytopenia resolved after a single 300 µg subcutaneous dose in one patient (PMID:1384817) and after doses on days 4, 5, 6, and 8 in another (PMID:7530779). Katz et al. conclude: "The use of G-CSF appears to be beneficial in alleviating bone marrow depression in colchicine overdose situations." The 2010 systematic review folds it into the standard of care: "Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment" (PMID:20586571).

The Chinese series adds thrombopoietin: "Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia" (PMID:34484680).

NCIT suggestions: NCIT:C1474 Filgrastim (verified), NCIT:C26078 Granulocyte Colony-Stimulating Factor (verified), NCIT:C15986 Pharmacotherapy (verified, generic action). Gene: CSF3 HGNC:2438.

Extracorporeal support and elimination

The distinction to hold onto: extracorporeal support works; extracorporeal elimination does not. Colchicine's large volume of distribution and intracellular binding put it out of reach.

  • Only 5.2% of a dose was recovered in dialysate in a formal renal-impairment PK study (PMID:25385362).
  • In a monitored poisoned child: "We observed no significant clearance from renal replacement therapy, nor activated charcoal, during this period... extracorporeal techniques do not seem to improve colchicine elimination" (PMID:33898365).

Support, by contrast, has saved lives. A 68-year-old with an ejection fraction of 5–10% survived on venoarterial ECLS: "ECLS allowed good cardiac contractility recovery within a few days, with complications including bleeding made controllable" (PMID:26230148). It is not universally successful — a 2024 report documents the challenges and limitations of VA-ECMO plus a microaxial flow pump in colchicine overdose (PMID:39484332), and a 13-year-old died despite VA-ECMO and exchange transfusion (PMID:37222938).

Plasma exchange has recent support. One 2025 case describes complete recovery with early therapeutic plasma exchange plus G-CSF and intensive care (PMID:41151150), and plasma exchange combined with continuous veno-venous haemodiafiltration "can increase survival time" in the 43-case series (PMID:34484680). NCIT: NCIT:C15304 Plasmapheresis (verified); NCIT:C171507 Extracorporeal Membrane Oxygenation (verified); NCIT:C15248 Hemodialysis (verified). No exact-label NCIT term resolved for continuous renal replacement therapy — flag.

Adjuncts of uncertain benefit

  • N-acetylcysteine for colchicine-associated liver failure. Used off-protocol; liver enzymes normalised 48 hours after administration in one case, though the patient still died (PMID:34229452). The authors are explicit that no protocol exists. CHEBI CHEBI:22198 acetylcysteine; NCIT NCIT:C200 Acetylcysteine (both verified).
  • Intravenous lipid emulsion. Used in a Colchicum autumnale case that recovered (PMID:42043136) and in a surviving dog (PMID:31883205). The 2026 nursing review calls IV lipid emulsion and NAC "promising" (PMID:42618164). That is case-level evidence, and it should be curated as such.

The experimental antidote — colchicine-specific Fab fragments

The one intervention aimed at the lesion itself. Goat-derived colchicine-specific Fab produced full recovery in a woman who ingested 60 mg, published in the New England Journal of Medicine (PMID:7845428; no abstract is indexed, so I quote no text from it).

The definitive preclinical study is the Göttingen minipig model (PMID:29334816). It answers the timing question and it is unambiguous: "Colchicine-specific Fab given early, in equimolar dose, bound colchicine, eliciting its movement into the blood, and preventing severe toxicity. Clinical studies are now needed to determine how soon this antidote must be given to work in human poisoning." The internal contrast is the finding: full-neutralising Fab at 6 h "did not prevent toxicity (euthanasia at 29.1 [SD = 3.4] h)", while the same dose at 1 or 3 h gave "survival to study end without marked cardiotoxicity."

It remains unavailable. "Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available" (PMID:20586571). Not licensed in the United States or Europe as of the most recent reports.

Pharmacogenomics of treatment

None. There is no genotype-guided therapy for colchicine poisoning. ABCB1 genotype is a susceptibility question, not a treatment-selection one.

Gene, cell, RNA, targeted, and immunotherapies

None applicable, with the single exception that the Fab antidote is an antibody-fragment biologic. No gene therapy, no CRISPR, no ASO or siRNA, no CAR-T, no checkpoint inhibitor has any role.

Surgery

No surgical intervention treats colchicine poisoning. Vascular access for ECMO/ECLS and dialysis is procedural, not therapeutic.

Treatment algorithm

  1. Establish the exposure history. Contact poison control. Colchicine looks like sepsis and like gastroenteritis; the history is the diagnosis.
  2. Decontaminate if early — charcoal, lavage only for very large ingestions inside 60 minutes.
  3. Admit to intensive care regardless of how well the patient looks. Deterioration is delayed and steep.
  4. Aggressive fluid and electrolyte resuscitation; vasopressors for shock.
  5. Serial full blood counts. Give G-CSF for neutropenia. Consider thrombopoietin for thrombocytopenia.
  6. Blood products for DIC and bleeding.
  7. Renal replacement for uraemia and volume — for organ support, not for drug removal.
  8. Consider ECLS/VA-ECMO for refractory cardiogenic shock.
  9. Consider plasma exchange, NAC, and lipid emulsion as adjuncts on case-level evidence.
  10. Watch for neutropenic sepsis. Cover it early.

13. Prevention

Prevention is where nearly all the achievable benefit sits, because treatment is supportive and the antidote does not exist.

Primary prevention

  • Do not co-prescribe colchicine with a dual CYP3A4/P-gp inhibitor. The strongest single recommendation in the field (PMID:16007523): "Since there are other drugs for treatment of pneumonia and gout, these 2 drugs should not be coprescribed, because of the risk of fatality." Reinforced by FAERS-wide signal detection: "Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended" (PMID:36688283).
  • Dose reduction in renal or hepatic impairment. "For those with liver or kidney dysfunction, the dose of colchicine needs to be reduced" (PMID:34229452).
  • Dose ceilings. Population PK modelling supports ≤ 1.5 mg daily as carrying low toxicity risk, with the caveat that "Higher colchicine dosages of > 1.5 mg daily may exceed the proposed upper limit of safety in individuals with low body weight who are taking statins" (PMID:40719983).
  • Plant misidentification education. Wild garlic vs autumn crocus (PMID:42043136); ginger vs Gloriosa tuber (PMID:41628608). This is public health education with a concrete target.
  • Household medicine storage, given the under-5 accidental peak (PMID:42499431).
  • Agricultural pasture management to keep Colchicum autumnale out of forage, which protects livestock and the milk supply (PMID:40905265).

Secondary prevention

  • Serial blood-count monitoring in patients on long-term colchicine with renal impairment or an interacting drug. The myelosuppression review targets exactly this group: "The majority of patients with myelosuppression had preexisting renal impairment or concomitant CYP3A4 or P-gp inhibitor use. Caution should be taken in this subset of patients with increased monitoring" (PMID:36319015).
  • Consider colchicine in any patient on the drug who presents with proximal weakness or unexplained cytopenia. The 23-year case is the cautionary one (PMID:35047617): "the patient's medication history should never be ignored."
  • Early recognition and poison-centre involvement in suspected acute exposure.

Tertiary prevention

  • Withdraw colchicine at the first sign of neuromyopathy. Resolution follows in 70% of cases at a median 21 days (PMID:36512928).
  • Rechallenge, if needed, at reduced dose: 73% of 15 rechallenged patients had no recurrence (PMID:36512928).
  • Neutropenic precautions and early antimicrobial cover during the marrow phase.

Not applicable

Immunisation, genetic screening, carrier screening, preimplantation or prenatal testing, and genetic counselling have no role. Record as not applicable.

Risk stratification

Electronic prescribing alerts on the colchicine + CYP3A4/P-gp inhibitor pair, and renal-function-linked dose checks, are the practical tools. No validated clinical risk score exists for pre-exposure risk; the 2026 nomogram is post-exposure and unvalidated (PMID:42522392).

14. Other Species and Natural Disease

Colchicine poisons every animal tested. There is no species-specific resistance mechanism, because the target is conserved tubulin.

Taxonomy of affected species (NCBI Taxonomy identifiers given as leads; I resolved MONDO, HP, GO, CL, UBERON, CHEBI, and NCIT against OLS this session, but not NCBITaxon):

Species Common Evidence
Bos taurus Cattle Fatal experimental and natural poisoning; 11 calves fed crude or dehydrated Colchicum bulbs all died or were euthanised within 63 h (PMID:9764409). A fatal heifer case confirmed by mass spectrometry (PMID:20093699). Herd exposure in a Swiss dairy (PMID:40905265).
Canis lupus familiaris Dog One fatal accidental ingestion of an owner's medication, euthanised at ~24 h (PMID:14992256); one survival after a tenfold prescribing error (PMID:31883205).
Rattus norvegicus Rat Experimental toxicity and Fab studies (PMID:41547239, PMID:25858137).
Mus musculus Mouse Crypt apoptosis, passive-immunisation studies (PMID:15865323, PMID:2815097).
Sus scrofa (Göttingen minipig) Pig Purpose-built critical-care toxicity model (PMID:29334816).
Oryctolagus cuniculus Rabbit Active immunisation against colchicine (PMID:2734802).

Breeds. Brown Swiss cattle in the Swiss dairy incident (PMID:40905265); a toy poodle cross (PMID:14992256) and a Pomeranian (PMID:31883205) in the canine reports. No breed predisposition — these are exposure accidents, not breed traits. VBO identifiers not resolved.

Orthologous genes. Tubulin and ABCB1 orthologues are broadly conserved across mammals. I did not resolve NCBI Gene identifiers for the animal orthologues.

Natural disease and veterinary importance. Substantial in ruminant medicine, where autumn crocus in pasture or hay is a recognised livestock hazard in northern and eastern Germany and elsewhere (PMID:11413718). Small-animal poisoning is accidental household or prescribing exposure. Canine presentation mirrors human: "Gastrointestinal signs, symptoms of cerebral edema, cardiac arrhythmias, and neutropenia were documented" (PMID:31883205).

Comparative pathology. The cross-species similarity is close enough to be diagnostically useful. From the calf study (PMID:9764409): "The lesion of the present acute crocus poisoning of cattle closely resembled those reported in humans with colchicine intoxication." Same targets: alimentary epithelium, haematopoietic and lymphoid tissue, renal tubular epithelium, Kupffer cells. Same mechanism: apoptosis of arrested dividing cells (PMID:10458107).

Evolutionary conservation. The colchicine-binding site on tubulin is conserved across eukaryotes, which is why colchicine works as a mitotic-arrest reagent in plants, fungi, and animals, and why the poisoning is species-general.

Zoonotic potential and cross-species transmission. None — this is a chemical exposure, not an infection. There is, however, a genuine food-chain transfer route: colchicine appears in milk from exposed dairy cattle, with a bulk sample positive at two weeks and negative at five weeks after the incident (PMID:40905265). Colchicine is not permitted as a pharmacologically active substance in food-producing animals under EU Regulation No 37/2010, and no maximum residue limit or withdrawal period exists.

15. Model Organisms

No genetic model exists, and none is needed. Colchicine poisoning is induced by administering colchicine. Knockout, knock-in, transgenic, conditional, and humanised models are all not applicable as disease models. (A transporter-deficient model such as an Abcb1-null mouse would model the susceptibility, not the poisoning, and I found no published use of one for this purpose.)

Induced models

Model System Protocol Recapitulation Limitations Source
Göttingen minipig critical-care model Sus scrofa 0.25 mg/kg colchicine IV over 1 h Best available. "intravenous infusion of 0.25 mg/kg colchicine over 1 h produced reproducible pharmacokinetics (AUC0-20 343 [SD = 21] µg/L/h), acute multi-organ injury, and cardiotoxicity requiring euthanasia a mean of 22.5 (SD = 3.2) h after dosing." Purpose-built for antidote timing. Intravenous, so it bypasses the gastrointestinal phase and first-pass metabolism entirely. Oral dosing was tried and abandoned: "Initial studies indicated that oral dosing produced variable pharmacokinetics and time-to-euthanasia." The 22-hour endpoint precedes the human marrow phase, so myelosuppression is not modelled. PMID:29334816
Rat acute lethal model Rattus norvegicus, Sprague Dawley, n = 60 Single oral 4.9 mg/kg; death in 8–10 h Forensic post-mortem biochemistry in skeletal, cardiac, and smooth muscle. Time-dependent falls in pH, Na⁺, ATP, glycogen; rises in CRP, LDH, Ca²⁺, K⁺, lactate. Death at 8–10 h models only hyperacute toxicity. Immunohistochemistry for cytochrome c oxidase and Na⁺/K⁺-ATPase did not differ between groups — a negative result worth carrying. PMID:41547239
Bovine feeding model Bos taurus, 11 calves Crude or dehydrated Colchicum autumnale bulbs, oral Recapitulates the human histopathology closely; established apoptosis as the death mechanism by TUNEL and electron microscopy. Plant material, so the exposure includes demecolcine alongside colchicine. All animals died within 63 h. Ruminant gastrointestinal anatomy differs (forestomach, abomasum). PMID:9764409, PMID:10458107
Mouse crypt-apoptosis model Mus musculus, C3H/S Single i.p. colchicine, sacrifice 4 h later Models the phase-1 target lesion specifically: crypt enterocyte apoptosis, highest in the deepest crypt regions. Single-tissue, single-endpoint. Also shows circadian dependence — "the colchicine cytotoxicity due to its apoptotic-inducing effect depends on the dosing time during the 24 h in this mouse strain" — which means dosing time is a confounder in every rodent colchicine experiment. PMID:15865323
Rat and rabbit Fab-clearance models Rat, rabbit Colchicine ± specific antibody or Fab Antidote pharmacokinetics only. Fab fragments enhance urinary colchicine clearance in the rat. Disposition models, not disease models. Do not use them to support a clinical-outcome claim. PMID:25858137, PMID:1545388, PMID:2734802, PMID:2815097
Beagle sustained-release PK model Canis lupus familiaris Colchicine sustained-release microspheres Formulation work on toxicity mitigation Pharmaceutical development, not poisoning PMID:41759985 (title-level; abstract not read)

In vitro

No dedicated organoid, iPSC, or organ-chip model of colchicine poisoning was located. Colchicine is ubiquitous as a reagent in microtubule cell biology, which is a different thing and should not be curated as disease-model evidence. Lymphocyte efflux experiments with colchicine-specific Fab exist (PMID:7562471).

Applications and gaps

What the models answer well: antidote timing (minipig), mechanism of cell death (cattle, mouse), post-mortem forensic markers (rat), antidote pharmacokinetics (rat, rabbit).

What no model currently answers: the human myelosuppressive phase, which is the phase that most drives clinical management. Every acute model kills the animal before day 3. That is the most obvious gap in the field, and it means G-CSF, thrombopoietin, and plasma exchange rest on human case-level evidence with no preclinical counterpart.

Resources

MGI, RGD, and the Alliance of Genome Resources index colchicine as a chemical perturbagen rather than as a disease model. There is no colchicine-poisoning model repository. Models are constructed per study.

Evidence source classification summary

For downstream curation, grading each citation by the study type it reports:

Evidence source PMIDs
HUMAN_CLINICAL 20586571, 34229452, 16007523, 3035372, 36512928, 36319015, 30888889, 41663238, 42499431, 34484680, 42522392, 37222938, 33898365, 26230148, 39484332, 41151150, 42043136, 1384817, 7530779, 9786547, 20661070, 35047617, 37813551, 8035398, 25385362, 40719983, 31178824, 42618164, 14164521
MODEL_ORGANISM 29334816, 41547239, 9764409, 10458107, 15865323, 25858137, 1545388, 2734802, 2815097, 14992256, 31883205, 20093699, 40905265
IN_VITRO 15014504 (X-ray crystallography of the tubulin–colchicine–stathmin complex), 7562471
OTHER 40136464 (systematic review of transporter genetics), 36688283 (spontaneous-report disproportionality analysis), 42589484 (narrative dosing reappraisal), 29359661 (narrative pharmacology review)

Note two grading subtleties for curation. First, PMID:36688283 is a FAERS disproportionality analysis — spontaneous reports, not a study of patients, and the reporting odds ratios are signals, not risks. Second, PMID:15014504 is structural biology; it supports the molecular mechanism claim and nothing clinical.

Confirmed gaps

Stated plainly, so nobody curates around them:

  • No sex ratio for colchicine poisoning incidence.
  • No quality-of-life instrument data.
  • No long-term survivor cohort or excess-mortality data.
  • No colchicine-poisoning transcriptomic, proteomic, metabolomic, lipidomic, single-cell, or spatial dataset located. No GEO series.
  • No epigenetic data.
  • No LOINC code resolved for a plasma colchicine assay.
  • No ECTO exposure terms resolved for colchicine or the two source plants.
  • Four NCI Thesaurus concepts did not resolve by exact label: gastric lavage, therapeutic plasma exchange, continuous renal replacement therapy, vasopressor agent.
  • The primary Bismuth publication behind the 0.5 / 0.8 mg/kg prognostic rule was not retrieved; every citation of it here is secondary.
  • PMID:7845428 (the NEJM Fab case) has no PubMed abstract, so no quote is available from it.
  • PMID:35237367, PMID:42053158, PMID:39870408, and PMID:41361680 are cited at title level only; their abstracts are not indexed in PubMed.

Sources

Primary literature is cited by PMID throughout. Web resources consulted:

Report summary. Colchicine poisoning is one molecular lesion — tubulin bound, microtubules unable to assemble — reaching every organ on different clocks. The gut and marrow fail first because they divide fastest; the heart fails because contraction needs an intact cytoskeleton; muscle and nerve fail slowest because axonal transport degrades over months. The liver and kidney injury closes a loop by slowing clearance of the poison. Mortality tracks dose, admission plasma concentration, age, and delay to presentation, but the classical 0.5/0.8 mg/kg prognostic rule is now contradicted from both directions by 2023–2026 data. Treatment is decontamination, intensive support, and G-CSF; extracorporeal circuits support the failing heart but do not remove the drug. The one mechanism-directed therapy, colchicine-specific Fab, works in the minipig if given within three hours and is not commercially available anywhere.

Reference Validation

Checked with linkml-reference-validator 0.2.1.

Outcome Count
References checked 59
Resolved 59
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 59
On topic 41
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 93
Resolved 86
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 7
Terms whose name was checked 19
Terms named correctly 18
Terms named as a different term 1

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • MONDO:0017859 (2 mentions) - the report calls it "MONDO"; MONDO calls it colchicine poisoning

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: ORPHA.