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Toxicity: pyrrolizidine alkaloid
Synonym(s): Ragwort toxicosis, Oral habout disease, Dunsiekte, Winton disease, Pictou disease, Suilkut disease, Schweinsberger disease
Introduction
- Pyrrolizidine alkaloids are toxins which mainly cause hepatotoxicity and liver failure but may also cause respiratory disease and renal damage depending on the plants involved.
- Cause: pyrrolizidine alkaloids are produced by 3 main plant families:
- Asteraceae (Senecio spp, tansy ragwort).
- Tobaceae (Crotalaria spp, rattlebox).
- Boraginaceae (Heliotropum, Amsinckia, Trichodesma and Echium spp).
- Signs: anorexia, weight loss, ventral edema, depression, icterus +/- signs of hepatic encephalopathy, eg apparent blindness, circling, head-pressing; respiratory distress.
- Diagnosis: liver function tests, hepatic biopsy, liver enzymes, alkaloids in liver, necropsy.
- Treatment: no effective specific treatment.
- Prognosis: poor if recurrent or severe.
Presenting signs
- Depends on plant species ingested.
- Signs of liver disease, eg anorexia, weight loss, ventral edema, icterus, depression, photosensitization.
- Signs of hepatic encephalopathy, eg head pressing, circling, respiratory distress.
- Signs of fever, tachcardia and severe respiratory distress.
Acute presentation
- Sudden anorexia, depression and icterus, hemoglobinuria.
- Death within 48 h.
- Severe respiratory distress.
Geographic incidence
- USA: ragwort, crotalaria and tarweed poisoning ('walking disease'), Senecio spp (all over USA), Crotolaria spectabilis (Southern States of USA), Gynoglossum officinale (Western USA).
- Australia: crotalaria poisoning ('Kimberley horse disease'; 'walkabout').
- New Zealand: ragwort poisoning ('Winton disease').
- South Africa: ragwort and crotalaria poisoning ('dunsiekte').
- Australia: heliotrope and echium poisoning ('walkabout' disease).
- UK: ragwort poisoning.
- Germany: schweinsberger brankheit.
- Russia: suiljut disease.
- Canada: pictou disease.
- South Africa: jaagsiekte; Crotalaris spp poisoning.
Age predisposition
- Usually adults.
- Yearlings (hepatic atrophy).
Cost considerations
- Cost of treatment.
Special risks
- Drugs as in hepatic failure Liver: hepatoencephalopathy.
- High mortality rate with repeated chronic exposure.
Pathogenesis
Etiology
- Pyrrolizidine alkaloids produced by plants.
- Ragwort (Senecio jacobea)
- contains 8 alkaloids, including retrorsine. - Heliotrope contains several alkaloids, including lasiocarpine and heliotrine.
- Crotalaria spp contain mainly monocrotaline, some also contain fulvine and crispatine.
Predisposing factors
General
- Plants containing pyrrolizidine alkaloids are usually, but not always, unpalatable and mostly ignored.
- May be consumed when there is little alternative feed.
- Dead ragwort and other pyrrolizidine alkaloid plants, eg in hay, are more palatable.
- Repeated ingestion of small amounts over several seasons may → disease - cumulative effect.
Pathophysiology
- Pyrrolizidine alkaloids have primary toxic effect on hepatic parenchyma and secondary effects on hepatic veins, pulmonary tissues and other extrahepatic tissues such as the lungs, kidneys and heart.
- Clinical signs occur once liver damage has progressed sufficiently to compromise liver function.
- Alkaloids → primary toxic effect on liver parenchyma → megalocytosis → necrosis and inhibition of cell division.
- Reactive alkaloids crosslink DNA, impair cell division and may affect protein synthesis.
- Can interfere with copper excretion.
- Secondary toxic effect on centrilobular and hepatic veins → endothelial damage and perivascular fibrosis → vascular occlusion.
- Apparent sudden onset, often weeks after ingestion has stopped → hepatic encephalopathy Liver: hepatoencephalopathy.
Timecourse
- Usually chronic.
- Liver damage may accumulate over several years.
- Onset of clinical signs may occur several weeks to months after ingestion of plant has stopped.
Epidemiology
- Plants are not usually palatable, therefore ignored unless food is scarce.
- Dead plants, eg in hay, are readily eaten.
- Toxicity is cumulative; liver damage may occur over several seasons.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Bothia C J et al (2012) Crotalariosis equorum ("jaagsiekte") in horses in southern Mozambique, a rare form of pyrrolizidine alkaloid poisoning. J Vet Diag Invest 24 (6), 1099-1104 PubMed.
- Creeper J H et al (1999) Pyrrolizidine alkaloid poisoning of horses grazing a native heliotrope (Heliotropium ovalifolium). Aust Vet J 77 (6), 401-402 PubMed.
- Curran J M, Sutherland R J & Peet R L (1996) A screening test for subclinical liver disease in horses affected by pyrrolizidine alkaloid toxicosis. Aust Vet J 74 (3), 236-240 PubMed.
- Winter H et al (1993) Pyrrolizidine alkaloid poisoning of yaks - diagnosis of pyrrolizidine alkaloid exposure by the demostration of sulphur-conjugated pyrrolic metabolites of the alkaloid in circulating haemoglobin. Aust Vet J 70 (8), 312-313 PubMed.
- Pearson E G (1991) Liver failure attributable to pyrrolizidine alkaloid toxicosis and associated with inspiratory dyspnea in ponies - 3 cases. JAVMA 198 (9), 1651-1654 PubMed.