5 Equine Intoxications

Yellow Star Thistle (Centaurea solstitialis)

• Introduced from the Mediterranean, yellow star thistle is now common in the western United States
• It's an invasive weed in cultivated areas, roadsides, and waste areas
• The plant is an annual herbaceous weed reaching up to 12 inches (30 cm) tall
• Its disc flowers are yellow and fertile
• The plant has stiff yellow spines, 0.5 to 1 inch (1 to 2 cm) long
• Neurotoxic components include aspartic and glutamic acids, solstitialin A 13- acetate, and cynaropicrin
• Contains a dopaminergic neurotoxin similar to the compound that causes Parkinson's
• The plant destroys the dopaminergic nigrostriatal pathway, affecting prehension and chewing
• Yellow star thistle is poisonous to horses in both green and dried states
• Horses develop a preference, eating it in all growth stages
• Signs of toxicity appear after 30 to 60 days of consumption in large quantities
• Horses need to eat 86 to 200% of their body weight in green thistle for clinical signs to appear
• Russian knapweed is also toxic to horses, causing similar signs, and requires less plant mass to be toxic

Chewing Disease

• Prolonged consumption of yellow star thistle or Russian knapweed causes "chewing disease" in horses
• Chewing disease includes increased tonicity and incoordination of chewing muscles
• Hypertonicity of facial muscles causes a "grimace"
• Food is held in the mouth, and constant chewing causes frothing of saliva that may resemble rabies
• Swallowing remains unaffected
• Some horses submerge their heads in water to reach the pharyngeal area for swallowing
• There is no effective treatment, as affected brain areas undergo liquefactive necrosis and do not regenerate

White Snakeroot (Eupatorium rugosum)

• White snakeroot is palatable, especially in late summer and fall, and can be lethal
• Leaves, stems and flowers are the most toxic parts
• It grows in woods, damp pastures and thickets
• Drying does not eliminate the toxin
• The toxic component is tremetol
• A toxic dose of the green plant is 1-10% of the animal's body weight at once or over time
• The toxin is cumulative
• All grazing animals are susceptible, and the toxin passes into milk
• Symptoms include depression, stiff gait, sweating, temperature changes, labored breathing, muscle tremors, throat paralysis, jaundice, hard feces, prostration, and sudden death
• Symptoms onset within 2 days to 3 weeks with death occurring within 1 day to 3 weeks
• Most horses succumb within 1 to 3 days
• Survivors might sustain permanent myocardial damage
• There is no specific treatment; clinical management is supportive; prognosis is poor to grave
• Remove other animals from pasture and fence wooded areas, especially in the fall and winter
• Continue milking lactating animals, but discard the milk

Red Maple Toxicity (Acer rubrum)

• Acer rubrum is a genus of about 150 deciduous shrubs to large trees native to North/Central America, Europe, Asia, and North Africa
• In the fall, leaves turn shades of yellow to deep red
• Consumption of wilted or partially dried red maple leaves causes acute hemolytic disease in horses
• Fresh, green leaves are not toxic
• The toxin responsible for hemoglobin oxidation is unknown but extracts from maples including A. rubrum, A. saccharum, A. saccharinum incubated with horse RBCs increased methemoglobin formation
• The "Acer fraction" causing methemoglobinemia contains gallic acid and other oxidants
• Horses develop depression, anorexia, dark urine indicating intravascular hemolysis
• A large amount consumed at once can cause acute depression, cyanosis, and death
• Hematocrit may drop to 10%
• Numerous Heinz bodies may be seen within red cells and persist for weeks
• Methemoglobin levels are markedly elevated
• Clinical management includes supportive care, IV fluids, and blood transfusions for anemia with a guarded prognosis

Foxglove (Digitalis purpurea)

• Digitalis has 22 species native to Europe, northern Africa, and western Asia
• Common species introduced into North America include Digitalis lanata, D. lutea, D. purpurea
• Toxicity is from cardenolides, especially digitoxin and digoxin
• All parts, especially seeds, are toxic, even when dried
• Animal poisoning occurs from grazing or garden clippings
• Early signs are colic and gastrointestinal issues
• Followed by weakness, rapid heart rate, changes in heart conduction decreasing cardiac output, hypotension, collapse, and death
• Gastric lavage with activated charcoal or mineral oil is appropriate

Toxic Plants Causing Hepatotoxicity

• Primary photosensitization is when a plant directly causes photosensitization. Hypericum perforatum (St. John’s wort) is an example
• Secondary photosensitization is when a plant causes hepatic disease, and severe hepatic disease leads to photosensitization. Senecio spp Ragwort is an example, and phylloerythrin accumulates in the skin

Pyrrolizidine Alkaloids (PAs)

• Pyrrolizidine alkaloids are hepatotoxins in many plant species.
• Most alkaloids are amino acid derivatives that repel insects and herbivores
• Important plants in the US include Amsinckia spp., Crotalaria spp., Cynoglossum spp., Echium spp., Heliotropium spp., and Senecio spp
• PA-containing plants are distributed throughout the United States and are most prevalent in the northwest regions
• These plants are unpalatable to livestock
• PA toxicosis occurs when pastures are overgrazed or in early spring with limited green forage
• PA concentrations do not decrease in fresh or dried plants
• Toxicity can occur via contaminated hay, silage, or grain at any time
• Pyrrolizidine alkaloid concentrations vary among plants, Senecio spp present the greatest risk to horses
• Daily consumption of Senecio plant material equivalent to 1-5% body weight causes hepatic disease in weeks in horses and cattle
• Ingestion of one Cynoglossum spp. plant a day for two weeks can cause clinical disease in a 500-kg horse
• Amsinckia spp, Crotalaria spp, Echium spp, and Heliotropium spp poisonings are less prevalent in the United States
• Cattle and horses are thirty to forty times more susceptible to PA poisoning than sheep and goats

PA Toxicity

• PAs are not directly toxic and are transformed in the liver to pyrroles by mixed function oxidases
• Pyrroles bind to cellular macromolecules like proteins and DNA, causing acute toxicity and tissue changes
• PAs or active metabolites may be detoxified by the liver for safe excretion
• Less reactive species at higher concentrations can damage other tissues like the lungs
• Metabolites other than pyrroles may also contribute to toxic effects
• Pyrrolizidine alkaloids are absorbed in the intestine and transported to the liver where they are metabolized to pyrroles
• Pyrroles are reactive, toxic metabolites that cross-link with double-stranded DNA
• They bind both proteins and nucleic acids within hepatocytes
• DNA binding has an antimitotic effect on hepatocytes, resulting in megalocyte formation that are replaced with fibrous tissue
• Liver failure results from hepatocellular death and fibrosis
• Clinical signs are consistent with liver failure
• The underlying lesion develops slowly over weeks to months, and clinical signs generally appear suddenly, and include anorexia, weight loss, depression, and behavioral abnormalities due to hepatic encephalopathy
• Diagnosis is based on history, clinical signs, lab abnormalities, and liver biopsy
• Clinical lab abnormalities include elevated gamma-glutamyl transferase, alkaline phosphatase, hyperammonemia, and increased bile acid concentration
• Hyperbilirubinemia is variable
• Liver biopsy shows megalocytosis, centrilobular and periportal fibrosis, and biliary hyperplasia
• There is no definitive treatment
• Prevent further exposure, and supportive care includes IV fluids, glucose, prophylactic antibiotics, and wound care for photodermatitis
• Lactulose may reduce signs of hepatic encephalopathy

Mycotoxins in Equine Patients

• Slobber toxin: Profuse salivation in horses and livestock consuming clover pasture or hay infected with Rhizoctonia leguminicola
• The mycotoxin is slaframine, an indolizidine alkaloid produced by the fungus R. leguminicola on red clover
• Treatment involves removing infected forage from the horses' diet
• Fescue toxicity: Tall fescue grass (Festuca arundinacea) is common in the US
• Neotyphodium coenophialum, formerly Acremonium coenophialum, is an endophytic fungus that infects tall fescue grass
• Ergopeptine alkaloids, primarily ergovaline, produced by endophytes, cause reproductive disorders in horses
• Pregnant mares grazing infected fescue have increased gestation lengths if exposed continuously or from day 300 of gestation
• Mares may carry foals for 370+ days
• Extended gestation causes dystocia, stillborn foals, and retained placentas
• Ergot alkaloids suppress prolactin production, resulting in poor udder development and decreased lactation is observed in fed endophyte-infected fescue
• Pregnant mares should avoid fescue pasture in the final 90 days of gestation
• Place mares with poor udder development on domperidone (1 mg/kg PO daily), a dopaminergic antagonist which will allow for enhanced prolactin secretion thereby facilitating improved lactation
• Moldy corn toxicity (leukoencephalomalacia): The mycotoxin produced by Fusarium proliferatum and Fusarium verticilliodes (Fusarium moniliforme) is fumonisin B1
• Horses are susceptible to this mycotoxin in corn-based diets due to seasonal predilection from fall through early spring
• Fumonisin B1 interferes with sphingolipid metabolism, disrupting endothelial cell walls and basement membranes, leading to liquefactive necrosis of the cortical white matter
• Concentrations greater than 10 ppm are toxic to horses
• Central nervous system disease with a cortical lesion is most common
• Severe hepatic disease is identified in cases that do not acutely succumb
• Therapeutic management is largely supportive, with a poor to grave prognosis
• Recovery from disease is unlikely after sufficient mycotoxin ingestion, as lesions are permanent
• The clinical condition is unlikely to resolve
• Ionophore intoxication: Monensin, lasalocid, salinomycin, narasin, and laidlomycin propionate are ionophore feed additives and/or coccidiostats
• Horses are often poisoned, though cattle and other species are also affected
• Clinical pathology changes, arrhythmias, and heart lesions are variable

Ionophore Mechanisms and Pathology

• Lipid soluble transports monovalent cations preferentially across cell membranes
• Monensin transports Na⁺ across lipid membranes
• Proton exchange for sodium leads to acidosis and potassium loss
• High intracellular sodium leads to secondary intracellular calcium overload
• Mitochondrial swelling, catecholamine release, and increased myocardial cell and diaphragm cell contractility
• Early positive inotropy
• Later negative inotropy and contracture
• Skeletal muscle and cardiac muscle dysfunction with potential failure
• Clinical signs appear within 12-72 hours of ingestion, with acute death, colic, anorexia, ataxia, and diarrhea
• Delayed deaths may occur after acute exposure and apparent recovery (cardiac fibrosis)
• Permanent cardiac damage is likely in sublethal cases
• In horses cardiac pathology is the predominant feature of the disease:
  • Edema
  • Pericardial and epicardial hemorrhages (tigroid appearance with pale streaking)
  • Histologic lesions of myocardial necrosis and secondary lesions associated with heart failure
• Prognosis is poor if signs are cardiac-related
• Early cases are managed by preventing further exposure, gastric lavage and mineral oil administration while Minimizing stress
• Fluids are used for shock, and electrolyte supplementation is needed
• Avoid cardiac glycosides

Blister Beetle Toxicosis

• Equine cantharidin intoxication or blister beetle toxicity should be considered in horses fed alfalfa hay exhibiting signs of colic, hypocalcemia, and azotemia
• There are over 200 species of blister beetles in the United States, belonging to the species, Epicauta
• The beetles swarm over small areas of vegetation so that large numbers are found in single bales of alfalfa from one location in a pasture
• Understanding the life cycle of blister beetles can play an important role in prevention
• Blister beetles have one generation per year laying eggs and dying within the calendar year
• Adult females lay up to 100 eggs in holes dug into the soil
• Eggs hatch into larva in the fall and eat grasshopper eggs
• Larvae become pupa and remain in the soil over winter
• Adults emerge in late spring and feed on alfalfa
• First and last cuts of alfalfa should be blister beetle free, and harvesting should coincide with the blister beetle life cycle
• Laboratory studies show cantharidin content varies from 1% to 11.3% of beetle dry weight with a common blister beetle containing <1% to >5%
• Experimentally, cantharidin doses of 0.45 to 1 mg/kg killed horses
• A striped blister beetle contains 5.4% cantharidin
• For a 1000-lb horse, a fatal dose is 81-128 beetles
• The small Epicauta species in New Mexico is gray with small black dots on the wing covers
• Symptoms are gastrointestinal distress (pawing, sweating, anxiety), anorexia, sham drinking where they submerge the muzzle but only drink small amounts of water
• Horses may have endotoxemia and die before diarrhea
• Many horses make attempts to void urine (stranguria)
• Synchronous diaphragmatic flutter and oral mucosal erosions (10%) are less common
• Clinical laboratory abnormalities are persistent hypocalcemia and hypomagnesemia, the development of hypoproteinemia, microscopic hematuria, and mild azotemia with inappropriate urine specific gravity
• Cantharidin concentrations in urine or pooled gastric-cecal contents are not always correlated with disease severity
• Blister beetle poisoning is not universally fatal
• Clinical signs relate to the amount of cantharidin ingested
• Necropsy lesions may be minimal
• Diagnosis must be confirmed by chemical detection of cantharidin in urine (500 ml TAMU), blood, or stomach or cecal contents

Preventing Blister Beetle Toxicosis

• Preventative measures are to harvest alfalfa hay at the right time.
• Inspect hay fields for beetle clusters before harvesting.
• Avoid harvesting areas with clusters.
• Suggested harvesting practices include:
  • Cut hay without using crimpers (may increase drying time).
  • Use a sickle bar mower without conditioner (slower, allows beetles to leave, does not crimp).
  • Avoid wheel traffic on standing or cut hay to prevent crushing beetles.
  • Cut hay prior to 10 percent bloom to minimize flower attractants.
  • Use small square bales for easy inspection.
  • Match cuttings and markets to the blister beetle season (early May and late September).
• Treatment dilutes and removes the toxin.
• Fluid therapy rehydrates the horse and lowers cantharidin concentrations.
• NSAIDs alleviate pain and protect against endotoxemia.
• Correct electrolyte abnormalities if present.
• Replace calcium carefully if levels are low.
• Give mineral oil to coat the stomach and intestines to lower absorption.
• Activated charcoal can be used, but must be followed by mineral oil to avoid absorption of activated charcoal.
• Prognosis depends on the amount of absorbed toxin and aggressive treatment.
• If the horse survives 2-3 days past ingestion, a more favorable prognosis is given.