Cantharidin is a potent vesicant and irritant produced by insects commonly known as blister beetles. Cantharidin can sometimes contaminate alfalfa. Cantharidin poisoning causes gastrointestinal and urinary tract irritation, and in severe cases can cause shock, circulatory collapse, and death. Cantharidin poisoning should be suspected in patients with compatible clinical signs, a history of alfalfa in the diet, and severe hypocalcemia and hypomagnesemia. Treatment includes correcting fluid and electrolyte imbalances, providing pain relief, and aiding elimination of cantharidin.
Cantharidin is produced by insects in the Meloidae family, commonly known as blister beetles. More than 200 species of these beetles are found throughout the continental US; however, the members of the genus Epicauta are most frequently associated with poisoning (toxicosis) in horses. Cantharidin is produced by adult male beetles and is transferred to females during copulation. The cantharidin content of individual beetles depends on species, sex, and breeding status. Blister beetles feed on floral and leaf parts of a variety of plants, including alfalfa. Some blister beetle species are gregarious, occasionally swarming in great numbers. Swarms in alfalfa fields often occur during the flowering stage.
Photograph of a blister beetle (Epicauta atrata) feeding on a yellow flower. Blister beetles feed on floral and leaf parts of a wide variety of plants.
Courtesy of University of Kentucky Entomology.
Photograph of a blister beetle.
Courtesy of University of Kentucky Entomology.
Photograph of a marginated blister beetle (Epicauta cinerea).
Courtesy of University of Kentucky Entomology.
Photograph of an oil beetle (Meloe proscarabaeus).
Courtesy of University of Kentucky Entomology.
Photograph of acute linear ulceration of the esophagus postmortem due to cantharidin toxicosis.
Courtesy of Dr. George Stoica.
This postmortem photograph shows acute gastric ulceration and hemorrhage of the cardia due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
This photograph of a section of the heart postmortem, shows extensive subendocardial hemorrhage due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
This photograph of a postmortem tissue specimen shows ecchymotic to suffusive hemorrhages of the urinary bladder due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
Photograph of a blister beetle (Epicauta atrata) feeding on a yellow flower. Blister beetles feed on floral and leaf parts of a wide variety of plants.
Courtesy of University of Kentucky Entomology.
Photograph of a blister beetle.
Courtesy of University of Kentucky Entomology.
Photograph of a marginated blister beetle (Epicauta cinerea).
Courtesy of University of Kentucky Entomology.
Photograph of an oil beetle (Meloe proscarabaeus).
Courtesy of University of Kentucky Entomology.
Photograph of acute linear ulceration of the esophagus postmortem due to cantharidin toxicosis.
Courtesy of Dr. George Stoica.
This postmortem photograph shows acute gastric ulceration and hemorrhage of the cardia due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
This photograph of a section of the heart postmortem, shows extensive subendocardial hemorrhage due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
This photograph of a postmortem tissue specimen shows ecchymotic to suffusive hemorrhages of the urinary bladder due to cantharidin toxicosis.
Courtesy of Dr. John Edwards.
Hay baled when a swarm is present can become contaminated with thousands of crushed beetles. Modern hay production practices such as crimping exacerbate the problem. Any product that contains alfalfa—including cubes, pellets, and treats—can also contain cantharidin. Toxic concentrations of cantharidin from dried fluids and beetle fragments can be present even if beetles are not grossly visible. Toxicity of cantharidin is not diminished by drying or storage. Although cantharidin contamination most often occurs in geographic areas such as the western US that is home to both blister beetles and alfalfa fields, cantharidin toxicosis can occur anywhere alfalfa is shipped. Cases have been documented in horses, cattle, sheep, goats, alpacas, dogs, cats, chickens, and emus.
Pathogenesis of Cantharidin Toxicosis in Animals
Cantharidin is rapidly absorbed from the gastrointestinal tract and is eliminated unchanged by the kidneys. Thought to alter mitochondrial membrane permeability, cantharidin is a potent vesicant and acantholytic agent, causing contact irritation of skin, gastrointestinal and urinary tract mucosa, and blood vessel endothelium.
In horses, endotoxemia can develop secondary to gastrointestinal mucosal injury. Direct myocardial damage has also been documented in horses with cantharidin toxicosis. The estimated minimum lethal dose of cantharidin in horses is 0.5–1 mg cantharidin per kg of body weight. As few as 4–6 g of dried beetles may be fatal to a horse.
Clinical Findings of Cantharidin Toxicosis in Animals
Clinical signs of cantharidin toxicosis can vary from mild gastrointestinal distress and depression to severe shock and death, depending on the dose. Affected animals may exhibit most of the expected clinical signs or only a few. In horses, the most common clinical signs are related to colic, ie, tachycardia, tachypnea, restlessness, depression, congested mucous membranes, increased capillary refill time, and sweating. Horses with gastric lesions may submerge their muzzles or appear to play in water tubs. Diarrhea, synchronous diaphragmatic flutter, muscle tremors, hyperthermia, and frequent, painful attempts to urinate are additional common clinical signs. Less common clinical signs include hematuria, stiff gait, oral lesions, and salivation.
Diagnosis of Cantharidin Toxicosis in Animals
Pertinent history (ie, alfalfa in diet)
Characteristic clinical pathologic findings
Cantharidin toxicosis should be considered in animals with compatible clinical signs and a history of alfalfa in the diet, whether as hay, cubes, pellets, treats, or from other sources. Common clinical pathology findings include profound hypocalcemia, hypomagnesemia, and increased PCV. Urine specific gravity may be low, even in dehydrated animals. Creatine kinase activity may also be increased. Urine and intestinal contents can be analyzed to detect cantharidin with gas chromatography–mass spectrometry or high-performance liquid chromatography. Liver, kidney, and serum analyses can be performed; however, these are not ideal samples.
Treatment of Cantharidin Toxicosis in Animals
Fluid and electrolyte replacement
Pain management
There is no antidote for cantharidin toxicosis. Treatment is focused on restoring fluid volume and electrolyte concentrations, particularly calcium and magnesium; managing pain; and enhancing elimination of cantharidin. Severely affected animals need volume resuscitation to restore and maintain perfusion and glomerular filtration rate. Large animals suffering from shock and circulatory collapse can require massive quantities of fluids. Hypocalcemic and hypomagnesemic animals require calcium and magnesium supplementation, possibly for prolonged periods. Several forms of parenteral calcium and magnesium are available. Extreme care should be taken when calculating doses. Dosages and product concentrations may be expressed as mg/kg, mg/mL, mEq/kg, mEq/mL, mmol/mL, mmol/kg, or percentages, and miscalculations can cause fatal overdoses. NSAIDs can be considered for analgesia in mild cases; however, they should not be used in dehydrated animals until fluid deficits have been corrected. In dehydrated animals, or in cases in which NSAIDs are ineffective, opioids may be a better analgesic option.
Decontamination per se is rarely practical, owing to the rapid absorption of cantharidin; however, enhancing elimination of cantharidin can be considered once the animal is stable. Activated charcoal may be useful if administered early. Di-tri-octahedral smectite can help adsorb endotoxins in horses. Mineral oil is not effective and may exacerbate cantharidin toxicosis. Additionally, mineral oil administered with or in close proximity to activated charcoal decreases the ability of activated charcoal to adsorb toxicants, including cantharidin.
Prevention of Cantharidin Toxicosis in Animals
Eliminating alfalfa from the diet is the most effective way to prevent cantharidin toxicosis. Risk can be decreased by purchasing alfalfa hay that has not been crimped and that was cut before the bloom stage or after a frost when blister beetle activity is lowest. Hay can be examined for blister beetles, although thorough examination of each flake is time consuming and impractical. Likewise, examination of processed alfalfa products such as cubes and pellets is not feasible.
Key Points
Cantharidin toxicosis in animals is often associated with feeding of contaminated alfalfa.
Prognosis depends on the amount of cantharidin ingested and timeliness of treatment; patients may need aggressive IV fluid treatment, calcium and magnesium supplementation, and analgesia.
Activated charcoal treatment can be considered to enhance elimination of cantharidin; however, mineral oil administration is contraindicated.
For More Information
Also see pet health content regarding cantharidin poisoning (blister beetle poisoning).
