Lupines (Lupinus spp) cause two distinct forms of poisoning in livestock: lupine poisoning and lupinosis. The former is a nervous syndrome caused by alkaloids present in bitter lupines; the latter is a mycotoxic disease characterized by liver injury and jaundice, which results mainly from the feeding of sweet lupines. Lupinosis is important in Australia and South Africa and also has been reported from New Zealand and Europe. There is increasing use of sweet lupines, either as forage crops or via feeding of their residues after grain harvest, as strategic feed for sheep in Mediterranean climate zones. Sheep, and occasionally cattle and horses, are affected, and pigs, goats, and donkeys are also susceptible.
Etiology and Pathogenesis of Mycotoxic Lupinosis in Animals
The causal fungus is Diaporthe toxica (formerly Phomopsis leptostromiformis), which causes Phomopsis stem-blight, especially in white and yellow lupines. Western Australia has developed lupine resistance to Diaporthe colonization of the plant in all current, commercial, narrow-leafed lupines in that region. The fungus produces sunken, linear stem lesions that contain black, stromatic masses, and it also affects the pods and seeds. The fungus is also a saprophyte and grows well on dead lupine material (eg, haulm, pods, stubble) under favorable conditions. It produces phomopsins as secondary metabolites on infected lupine material, especially after rain. Lupinosis occurs primarily in summer and autumn when livestock graze dead lupines. Once lupines produce phomopsins in the forage, the stubbles can remain toxic for several months to years.
Clinical Findings, Lesions, and Diagnosis of Mycotoxic Lupinosis in Animals
Toxic hepatocyte injury
Gross pathological lesions
Early clinical signs in sheep and cattle are inappetence and listlessness. Complete anorexia and jaundice follow, and ketosis is common. Cattle may show lacrimation and salivation. Ketosis is a common sequela in pregnant cattle or recently calved cows. Survivors may develop hepatic cirrhosis. The secondary complications to acute liver damage are lupine-associated myopathy in young sheep that does not apparently respond to traditional selenium or vitamin E treatment as well as hepatoencephalopathy associated with hyperammonemia that can result from an inability of the liver to metabolize ammonia from the higher crude protein in lupine seeds. Sheep may become photosensitive, and a skeletal muscle myopathy can develop, resulting in hunched backs and a reluctance to move. As disease progresses, liver failure may cause hepatoencephalopathy characterized by stumbling, disorientation, and recumbency before death. In acute outbreaks, deaths occur in 2–14 days. Generally, if a patient continues to eat, death does not occur.
Clinical changes are mainly attributable to toxic hepatocyte injury, which causes mitotic arrest in metaphase, isolated cell necrosis, and hepatic enzyme leakage, with loss of metabolic and excretory function. Biochemical changes are associated with increased serum hepatic enzyme activity and bilirubin concentration. If the animals have lupinosis-associated myopathy, serum creatine kinase activities are increased and with concurrent damage to the kidneys and adrenal cortex, the serum concentrations of urea, creatinine, and magnesium are increased and concentrations of sodium and bicarbonate are decreased.
In acute disease, icterus is marked. Livers are enlarged, orange-yellow, and fatty. More chronic cases show bronze- or tan-colored livers that are firm, contracted in size, and fibrotic. Copious amounts of transudates may be found in the abdominal and thoracic cavities and in the pericardial sac. Some animals may have spongiform lesions in the brain.
Gross lesions in the acute and subacute lupinosis can reveal a large swollen liver, bright yellow to orange in color, and enlarged gallbladder. Frequently ascites and edema of connective tissues occur. With a myopathy, skeletal muscles and occasionally cardiac muscle can have areas of subtle pale streaking. In chronic lupinosis, the liver is small, hard, coppery to tan in color and misshapen with possible evidence of muscle wastage.
Diagnosis is based on knowledge that animals are being fed moldy lupine material, which, together with clinical signs and increased levels of serum liver enzymes, strongly indicates lupinosis.
Control of Mycotoxic Lupinosis in Animals
Use of resistant lupine cultivars and surveillance for fungal infection
Good sheep management practices
The use of lupine cultivars bred and developed for resistance to Diaporte toxica (P leptostromiformis) is advocated. Frequent surveillance of lupine fodder material for characteristic black spot fungal infestation, especially after rains, is advised.
Sheep management practices recommended are: grazing the lupine stubble immediately after harvest, providing young stock access to lupine seeds for a few day prior to placing on lupine stubble, not overgrazing lupine stubble, providing adequate watering facilities, and frequent surveillance of sheep for lethargy, which is the first indication of the development of lupinosis.
No specific treatment is available. The aim of treatment is to stop access to the toxic feed and stimulate an appetite in animals by providing good quality hay and supplementary feeds in cereal grains. Animals should not be fed high-protein grain or supplemented with urea. Veterinarians may consider providing vitamin B12 (by injection) and stimulating rumen movement. Animals on green pasture should be provided access to shade. Administration of zinc (≥0.5 g, PO, every 24 hours long term) protect sheep against liver injury induced by phomopsins.
Lupinosis is a liver disease or hepatotoxicosis caused by ingestion of lupine plants infected with Diaporthe toxica (previously identified as Phomopsis leptostromiformis) that primarily affects sheep in Australia and South Africa.
With the introduction of lupine resistant cultivars to Diaporthe colonisation in narrow-leafed lupines, disease incidence has been reduced.
Clinical signs in animals include complete anorexia, jaundice, lethargy, ketosis in pregnant cattle, and secondary complications of myopathy and hepatoencephalopathy.
Diagnosis is based on the determination that animals are consuming moldy lupine stubble, compatible clinical signs of liver damage, and elevated serum liver enzyme activity and bilirubin concentration.
No specific treatment is available; animals should be prevented from further exposure to the moldy lupine stems, kept eating, provided with good quality hay and supplemental grain, and, sometimes, administered injectable vitamin B12 and oral doses of zinc to protect against liver injury induced by phomopsins.
For More Information
Allen J. Phomopsins. In: Plumlee KH, ed. Clinical Veterinary Toxicology. St. Louis: Mosby, 2004;259-262.
Hepworth K. Lupinosis in sheep. Government of Western Australia. Dept. of Primary Industries and Regional Development. Agriculture and Food.