In nature, cantharidin is found in beetles belonging to the Meloidae family. More than 200 species of these beetles are found throughout the continental USA, but members of the genus Epicauta are most frequently associated with toxicosis in horses. The striped blister beetles (E occidentalis, E temexia, and E vittata) are particularly troublesome in the southwestern USA. The black blister beetle, E pennsylvanica, has caused toxicosis in horses in Illinois. Cantharidin is the sole toxin, but its concentration in beetles varies widely.
Blister beetles usually feed on various weeds and occasionally move into alfalfa fields in large swarms. These insects are gregarious and may be found in hay in large numbers when it is baled. One flake of alfalfa may contain several hundred beetles, but a flake from the other end of the same bale may have none. Animals are usually exposed by eating alfalfa hay or alfalfa products that have been contaminated with blister beetles.
Cantharidin is an odorless, colorless compound that is soluble in various organic solvents but only slightly soluble in water. It is highly irritating and causes acantholysis and vesicle formation when in contact with skin or mucous membranes. After ingestion, it is absorbed from the GI tract and rapidly excreted by the kidneys. The minimum lethal oral dose in horses has not been established, but it appears to be <1 mg/kg body wt. As little as 4–6 g of dried beetles may be fatal to a horse. The toxicity of cantharidin does not decrease in stored hay, and cantharidin is also toxic to people, cattle, sheep, goats, dogs, cats, rabbits, and rats.
The severity of clinical signs associated with cantharidin toxicosis varies according to dose. Signs may range from mild depression or discomfort to severe pain, shock, and death. Typical signs are related to GI and urinary tract irritation, endotoxemia and shock, hypocalcemia, and myocardial dysfunction. The onset and duration of signs can vary from hours to days. The signs seen most frequently include varying degrees of abdominal pain, depression, anorexia, and frequent attempts to drink small amounts of water or submerge the muzzle in water. Some horses show only signs of depression or make frequent attempts to urinate. Urine may be blood-tinged or contain blood clots but frequently appears normal. A striking feature is that affected horses invariably have dark, congested mucous membranes, even if other systemic signs of toxicosis are minimal. Sweating, delayed capillary refill time, increased heart and respiratory rates, and increased rectal temperature are other common signs. Less frequent signs include oral erosions; salivation; synchronous diaphragmatic flutter; a stiff, short-strided gait; and diarrhea that may contain blood. Horses that ingest a massive amount of toxin may show signs of severe shock and die within hours.
Both high-performance liquid chromatography and gas chromatography or mass spectrometry analyses are sensitive, reliable methods of detecting cantharidin in gastric contents or in urine. The concentration of cantharidin in urine becomes negligible in 3–4 days, so urine should be collected early in the course of disease if it is to be analyzed. Microscopic evaluation of stomach contents (and often cecal contents) of fatally poisoned horses may reveal fragments of the insect, which can be positively identified if from one of the three striped species.
Certain laboratory findings are particularly helpful in differentiating cantharidin toxicosis from other causes of acute abdominal crisis. Serum calcium concentration is usually markedly decreased and may remain low for a prolonged time. Serum magnesium concentration is also typically low, and concentration of serum CK usually increases markedly within 24 hr of onset. In acutely affected horses, urinalysis typically reveals markedly decreased specific gravity (usually <1.010) and varying degrees of hematuria. Peritoneal fluid usually contains increased protein (>4 g/dL) but normal numbers of WBCs and normal fibrinogen concentration. Other laboratory abnormalities may include mild increases of serum urea nitrogen and creatinine and development of hypoproteinemia. Acutely affected horses are almost always hyperglycemic.
There is no specific antidote for cantharidin poisoning, but prompt, vigorous symptomatic therapy is necessary for a good outcome. Oral administration of mineral oil aids in evacuation of the GI tract, and repeated dosing may be indicated. Activated charcoal, PO, may be helpful if given early. Other oral adsorbents containing ditrioctahedral smectite might be helpful as well, but their efficacy has not been evaluated. Calcium and magnesium supplementation for prolonged periods is almost always indicated. Other symptomatic therapy includes administration of fluids, analgesics, and diuretics and maintenance of normal blood pH and serum electrolyte concentrations. The prognosis for affected horses improves daily if no complications occur.
Prevention is by feeding beetle-free hay. The hay field must be scouted before it is cut and during baling, because the insects can be crushed in the cutting and crimping process as well as during baling. Areas of the field that contain swarms of beetles must be avoided for a few days because most of the insects will leave. Once the beetles have left, these areas can be harvested.
First-cutting hay is almost always free of blister beetles, because the insects overwinter as subadults and usually do not emerge until late May or June in the southwestern USA. Likewise, the last cutting of hay is often safe, because it is usually harvested after the adult insects are no longer active.