Fatal colchicine intoxication by ingestion of Gloriosa superba tubers

Abstract

Gloriosa superba is an ornamental herb, wildly found in the tropics especially in the southern parts of India and Sri Lanka. All parts of the plants are toxic, especially the tuberous rhizomes in view of their high content of colchicines and its derivatives. We report a case of fatal ingestion of the tubers of G. superba, with an intention of deliberate self harm, leading to systemic coagulopathy and progressive multiple organ dysfunctions. The patient was managed with intralipid rescue therapy, plasmapheresis, haemodialysis and intensive care. The ease of availability makes plant poisons, a common method of deliberate self-harm in South India. This report reiterates the need for clinician’s awareness of common toxidromes associated with plant poisons.

Background

India ranks one of the highest among suicide rates, with the southern states having tenfold higher rates of suicide than the northern states.¹ The most common method of poisoning in the rural parts was pesticide consumption followed by other forms of poisoning such as consumption of plant poisons, in view of easy availability and accessibility. Gloriosa superba is a tropical herb, predominantly found widely in southern states of India and Sri Lanka.^{2 3} All parts of the plant are toxic, with the tubers having the maximum toxicity. The principal constituents contributing to toxicity include highly active alkaloids such as colchicine, superbrine, gloriosine, chelidonic acid and salicyclic acid.² The mechanism of toxicity is due to the effect of colchicine and gloriosine on the cell cycle, leading to arrest of cell mitosis in metaphase stages, predominantly targeting cells with rapid turnover such as bone marrow and intestinal epithelial cells. The lethal dose for humans is 0.8 mg/kg and ingestion follows a rapidly fatal clinical course.⁴ Multiple case reports exist from South India and Sri Lanka with case fatality rates as high as 15%. Management is essentially supportive with anecdotal reports showing benefit in plasmapheresis. We report a case of colchicine toxicity due to consumption of G. superba tubers, with a rapidly fatal clinical course despite aggressive intensive care, haemodialysis, plasmapheresis and intralipid rescue therapy.

Case presentation

An 18- year-old woman presented to the emergency department with an alleged history of consumption of G. superba tubers (figure 1). She presented with generalised abdominal pain associated with multiple episodes of non-bilious vomiting and loose stools. She was referred from a peripheral clinic following first aid, which included gastric lavage and fluid resuscitation.

Figure 1.

Gloriosa superba tuber.

On clinical examination, she was found to be pale, tachycardiac (110 beats/min) with signs of moderate dehydration. Physical examination revealed abdominal tenderness with the rest of the systemic examination being within normal limits. In the first 12 hours of hospital admission, she developed progressive oliguria and respiratory distress requiring intensive care and non-invasive ventilation.

Investigations

Laboratory investigations revealed a haemoglobin level of 110 g/L with white blood cell count of 12.6×10⁹/L with left shift and thrombocytopaenia (70×10⁹/L). Her coagulation parameters showed mild elevation (prothrombin time—17.8 s, international normalised ratio—1.68, activated partial thromboplastin time—53.7 s). She had elevated cardiac enzymes (creatinine kinase muscle brain isoenzyme (CKMB)—30.6 ng/mL, troponin T—17.1 pg/mL). She had rhabdomyolysis with creatine phosphokinase levels of 30 860/µL, which increased to 56 960/µL over a period of 12 hours. She had acute oliguric kidney injury (serum creatinine—1.52 mg %), hypoalbuminemia with transaminitis (albumin—2.8 g/dL, serum aspartate aminotransferase—1940 U/L, serum alanine transaminase—698 U/L) and metabolic acidosis (pH—7.27, bicarbonate—18.2). Chest radiography showed features of acute respiratory distress syndrome. Her laboratory parameters during the course of stay has been summarised in table 1.

Table 1.

Laboratory parameters of patient with Gloriosa superba poisoning

Variable	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6
Haemoglobin (g/L)	137	110	99	71	81	68
Total white bloodcell count (x 109/L)	32.9	13.6		0.3	0.2	1.6
Platelet count (x 109/L)	216	70	27	27	11	9
PT/INR (s)	25.2/2.29	17.8/1.63	12.3/1.12	1.06/0.97	10.9/1.0	12.4/1.14
APTT (s)	62.9	53.7	54.3	45.4	33.8	30.0
Fibrinogen (mg/dL)	274					417
pH	7.40	7.27	7.44	7.49	7.48	6.86
Bicarbonate (m mol/L)	18.2	17.3	23.1	28.2	28.3	7.6
Creatinine (mg%)	1.33	1.12	0.86	1.52	1.88	1.94
Total bilirubin (mg%)	0.54		0.69	1.64	1.70
Direct bilirubin (mg%)	0.23		0.31	0.96	1.48
AST (U/L)			1940	3105	1262	422
ALT (U/L)	30		698	1395	1120	452
Alkaline phosphatase (U/L)	530		297	124	63

ALT, serum alanine transaminase; APTT, activated partial thromboplastin time; AST, serum aspartate aminotransferase; INR, international normalised ratio; PT, prothrombin time.

Treatment

She was admitted in the medical intensive care unit for ventilatory and haemodynamic supports. She was initiated on non-invasive ventilation, and was subsequently initiated on mechanical ventilation. She continued to be anuric, hence was maintained on haemodialysis. She received blood products (fresh frozen plasma—15 mL/kg, cryoprecipitate—6 mL/kg) for disseminated intravascular coagulation. She was given a session of plasmapheresis. She was initiated on intralipid rescue therapy at 100 mL/day for two consecutive days. She developed pancytopenia secondary to bone marrow aplasia for which was unresponsive to granulocyte colony stimulating factor.

Outcome and follow-up

She continued to deteriorate, and despite all measures she progressed to develop cardiovascular collapse with refractory hypotension and succumbed to the toxicity in 8 days.

Discussion

G. superba belongs to the family colchicaceae, characterised by a climber plant which is commonly referred to as ‘flame lily’, ‘glory lily’, ‘climber lily’.^{2 5} The plant has a characteristic flower, which is the national flower of Zimbabwe. This plant is widely cultivated in Tamil Nadu, as a cash crop in view of high concentrations of colchicine and its derivatives, silosterol, betasilosterol and luteolin, which is typically extracted from the seeds.⁶ Accidental poisoning and suicidal use of parts of the plants are common in the areas of cultivation. Colchicine is rapidly absorbed from intestine and undergoes hepatic metabolism. Clearance of metabolites is predominantly through intestinal faecal excretion followed by renal clearance (10%–20%). Colchicine targets the cells in active mitosis by inhibition of polymerisation of microtubules.^{7 8} This results in varied manifestations including severe gastroenteritis, rhabdomyolysis, pancytopenia, metabolic acidosis, shock secondary to cardiovascular collapse and multiple organ dysfunction.^{8 9} The lethal dose is reported to be about 0.8 mg/kg which could be present in about 25 grams of tuber consumption.^{10 11} Colchicine is an alkaloid extracted from autumnal Colchicum plant which is used primarily for its anti-inflammatory therapy effect. Acute intoxication with colchicine is uncommon but often severe and results in multiple visceral organ dysfunctions. The intoxication severity and mortality depend directly on the ingested dose. The treatment is mainly symptomatic. However, the development of specific anti-colchicine immunotherapy would offer a new therapeutic perspective. Authors have also reported a case of a young patient who ingested 40 tablets colchicine, which caused multiple organ failure and with fatal outcome.¹⁰

The reported neurological toxicity includes ascending polyneuropathy and toxic encephalopathy.^{12 13} In a prospective cohort of 4556 poisoning patients in Sri Lanka, 2.5% were due to consumption of plant poison with the the most common (44%) being G. superba ingestion.¹⁴ Typical toxicity follows three sequential phases with phase I lasting from the initial 10–24 hours of consumptions where gastrointestinal symptoms predominate, followed by phase II which lasts 2–7 days, where multiple organ system dysfunction with fatality occurs. Phase III lasts from 1 week to 3 weeks where recovery occurs with significant alopecia.²

Treatment is essentially supportive. Demirkol et al had reported a case of colchicine intoxication which was successfully managed with plasma exchange.¹⁵ They hypothesised that plasma exchange might be beneficial by facilitating elimination of colchicine. The use of intravenous lipid emulsion enables the formation of intravascular lipid phase, which will act as a ‘sink’ to drive offending drugs which have been overdosed from target tissues to intravascular compartment to facilitate elimination.¹⁶ This option has been successfully used in management of toxicity due to a wide spectrum of drugs, pesticides and other compounds. However, there is no existing evidence for its use in colchicine toxicity. Colchicine specific Fab fragments was successfully used in management of severe colchicine toxicity, however its use is curbed by its high costs and less availability.¹⁷

Learning points.

• Clinicians practising in the tropical countries should be aware of common toxidromes of plant poisons especially Gloriosa superba toxicity in view of rapid clinical course and fatality.

• Colchicine toxicity can progress to multiorgan dysfunction syndrome in view of its cytotoxic mechanism of action.

• Management is essentially supportive, with no consistent benefit in using plasma exchange or intralipid rescue therapy.

• Colchicine specific Fab fragments can be successfully used in severe toxicity; however, the lack of availability and high costs limits its use in resource limited settings.