Death of a dog caused by calcipotriene toxicity

To the Editor: Frankenstein, a 19-pound, 1-year-old pug, often licked his owner's skin, especially after his owner applied calcipotriene ointment to treat chronic plaque psoriasis. One evening when the medication was left unattended, Frankenstein tore open the 30-g tube and ingested approximately 10 g of calcipotriene. After 48 hours, he developed hematemesis and extreme fatigue. His veterinarian contacted the American Society for the Prevention of Cruelty to Animals' poison control center and was given the recommended protocol for calcipotriene poisoning. She also learned that the dog's prognosis was poor, because of the extended period of time since ingestion and the inherent susceptibility of canines to the toxic effects of calcipotriene. Frankenstein's initial blood chemistries revealed hypercalcemia and hyperphosphatemia and elevated blood urea nitrogen, alanine aminotransferase, and secretory aspartyl-protease levels. His urine revealed proteinuria and hematuria. The American Society for the Prevention of Cruelty to Animals' protocol was started within a few hours, but despite the aggressive intervention, the dog passed away within hours.

The ointment contains 0.005% calcipotriene (50 μg/g), a synthetic vitamin D3 analog. Vitamin D3 analogues may have potent calcemic properties and are potentially more lethal when ingested at smaller doses as compared to parent vitamin D3 compounds.1 The introduction of synthetic vitamin D3 analogs in antipsoriasis petroleum-based ointments has led to numerous reports of toxicity in dogs in the United States and in the United Kingdom.2, 3, 4, 5 Clinical signs of calcipotriene toxicity usually present within 24 to 72 hours of ingestion and include anorexia, vomiting, diarrhea, polyuria, polydipsia, depression, and weakness.6 If left uncorrected, hypercalcemia in dogs can lead to primary renal failure and soft tissue mineralization.7 Reports of accidental ingestion of calcipotriene in dogs indicate that 40 to 60 μg calcipotriene per kilogram of body weight can cause severe hypercalcemia and a significant risk of mortality.8

While the veterinary literature contains several articles on the topic, we know of only one reference in human dermatologic literature.9 Topical calcipotriene is relatively safe in humans, and we are unaware of any reports of toxicity from oral ingestion in humans; however, the low threshold of calcipotriene toxicity in dogs raises concern.10 Small dogs are at risk even if the contents of a 30-g tube are only partially ingested. Patients are generally unaware of the potential toxicity of ingesting topical medications, which leads to a tendency to handle topical medications less cautiously than oral medications. We encourage specific counseling when prescribing calcipotriene, particularly for pet owners, in order to avoid further tragic pet deaths.