By Naomi Rich, DVM, ACVD Resident For The Education Center
Originally Published In Veterinary Practice News, January 2020 – Download as a PDF
The patient: a five-year-old male, neutered Labrador/poodle mix weighing 13 kg.
The dog has a four-year history of allergic disease and chronic ear disease. He was diagnosed with atopic dermatitis and otitis externa at one year of age and was skin-tested and started on allergen-specific immunotherapy, cyclosporine, at 3.67 mg/kg once daily for four weeks and then every other day thereafter. He also was treated for his ear disease. The dog remained pruritic after several months of allergen-specific immunotherapy and cyclosporine, so oclacitinib was started at 0.6 mg/kg once daily. The cyclosporine was discontinued due to a lack of efficacy in this patient and suspected association with vomiting episodes.
Approximately one year before presentation for oral papilloma, the owners discontinued the allergen immunotherapy and elected instead to continue oclacitinib at 0.6 mg/kg with an increased, twice daily dosing frequency. The dog required treatment for demodex mites approximately eight months before presentation for oral papilloma and was administered sarolaner at 2.9 mg/kg once monthly. Sarolaner was recommended to be continued monthly at this dose as a preventative.
Physical examination revealed multiple (five to eight) papillomatous growths on the superior and inferior lips, as well as the buccal mucosa. A similar growth was noted within the dorsal interdigital space of the second and third digit of the right front paw.
Step one: Client education and alteration of medications
The physical exam findings were discussed with the owner, along with the differential diagnosis of oral viral papilloma. In general, oral papillomas resolve without treatment in one to three months. It was recommended the owner keep a close eye on the dog’s oral cavity and eating habits, and to call us if he progressed or did not regress in the expected time period.
Approximately three weeks later, the owner called to report the lesions were markedly progressive and there was concern they would start to affect the dog’s ability to eat. The owner was interested in further treatments. Physical examination at this time revealed a marked increase in the number of papillomas, with numerous (25-plus) papillomatous growths in the oral cavity. The lesions involved a large percentage of the mucosal surfaces of the lips, the gingiva, the tongue, the roof of the mouth, and the soft palate extending up around the epiglottis and pharynx (Figure 1). Lesions on the lips had increased markedly in size, with a large papilloma situated on the rostral aspect of the inferior buccal mucosa (Figure 2). The lesion noted previously on the right front paw was unchanged.
Step two: Biopsy and histopathology
Biopsy samples were submitted for histopathologic examination, which confirmed a pathologic diagnosis of viral papilloma (Figures 3 and 4). Two biopsy samples were evaluated and found to be similar. Both contained a benign exophytic neoplastic proliferation of the squamous epithelium caused by infection due to the papillomavirus. There was marked epidermal hyperplasia with the papillae supported by dermal fibrovascular stroma, which contains foci of inflammation and prominent blood vessels. The overlying stratum corneum was hyperkeratotic with parakeratosis. The granular layer was prominent and the keratohyalin granules were large, round, and irregular. The spinous layer was hyperplastic, and in some cells, the normal eosinophilic cytoplasm was replaced by a pale basophilic cytoplasm (viral cytopathic effect). The basal layer was hyperplastic, with occasional suprabasal mitoses.
Step three: Systemic interferon therapy for the virus
The dog was started on interferon-alpha 2b (IFN) at 1 million units/M2 given twice weekly subcutaneously. When oral papillomas are ablated without additional therapy, we tend to see recurrence of numerous lesions within a few weeks post-surgery. Thus, we always use interferon in conjunction with laser ablation for these types of cases. At the same time, we have seen dogs return after four weeks of interferon therapy with marked regression of most of the oral papilloma, and surgery is not needed. Depending on the case and severity at the initial presentation, we start interferon alone and then if the oral papillomas remain persistent, we order another four-week course of interferon and start this simultaneous with the initial laser ablation surgery. We generally plan on possible follow-up laser ablation four to six weeks later if oral lesions remain or recur.
Step four: Laser ablation— Superficial layers of the smaller papillomas on the paw and lips
After four weeks of interferon therapy, the oral papillomas were less proliferative, but much of the mouth remained affected. The lesion on the right front paw was persistent and had become painful, manifesting in forelimb lameness. CO2 laser ablation surgery was scheduled.
The patient was sedated with dexmedetomidine and butorphanol at appropriate doses and then intubated for anesthesia using sevoflurane inhalant. The dexmedetomidine was reversed after a stable plane of anesthesia was reached. Robenacoxib injectable was given (1.3 ml) to provide pain control, and maropitant citrate was given for antiemetic and pain control properties (1.36 ml).
All the papillomas in the mouth, including those on the tongue, the gingival and buccal mucosa, the pharynx, and the paw, were ablated. Laser settings varied according to the depth. For the smaller lesions on the paw and on the lips, the initial setting was between 12 to 30 watts, continuous wave (CW), with the focusing tip at 0.25-mm spot size (Figure 5).
Step five: Laser ablation— Superficial layers of the larger papillomas on the tongue and in the mouth
The laser settings were 12 watts, SuperPulse, 20 Hz, 40 percent duty cycle with the focusing handpiece at either 0.25-mm or 0.8-mm spot size for the initial layers of ablation. The tip was then changed to the wide 3-mm ceramic tip and the settings were adjusted to 40 watts, CW for ablation of the upper layers of the papillomas and 15 watts, SuperPulse, 20 Hz, 40 percent duty cycle for the deeper layers.
Step six: Laser ablation—Layers close to normal tissue
The 3-mm ceramic wide tip was used with the laser settings at 20 to 30 watts, CW, and 20 to 30 watts, SuperPulse, 29 Hz, 78 percent duty cycle and varied throughout the surgical procedure depending on the depth of the ablation (Figure 6).
Step seven: Three-week reevaluation exam
At the three-week follow-up exam, the dog remained on systemic interferon therapy (IFN) and the majority of previously ablated lesions had healed with minimal to no scarring (Figures 7 and 8). Two new small (1- to 2-mm) papillomas were noted on the left margin of the tongue near where a large cluster of papillomas had been previously ablated (Figure 8). These lesions were ablated using a wide tip with the laser settings at 8 watts, SuperPulse, 20Hz, 40 percent duty cycle (Figure 9).
Step eight: One-month post-op exam
IFN therapy was continued and no new papillomas were noted. The patient remained on IFN therapy for a total of eight weeks at 0.5 million units IFN s.q. two times per week.
Step nine: Follow-ups every two months for the next six months
No recurrence of oral or cutaneous papillomas was noted at any of the follow-up examinations (Figure 10). The allergen-specific immunotherapy was reinstituted and the oclacitinib dose was recommended to be decreased to once daily or less as needed.
The dose of oclacitinib this patient was receiving is slightly higher than the recommended label dose of 0.5 mg/kg; it was needed twice daily long-term for pruritus control instead of the recommended once-daily dosing. Oclacitinib is known to cause a marked decrease in white blood cell values in some canine patients, resulting in bacterial, parasitic, and viral infections. It was strongly suspected this profound and persistent oral viral papillomatosis and previous history of demodicosis could be associated with the high dose and chronically increased dosing frequency of oclacitinib the patient was receiving.
Naomi Rich, DVM, ACVD Resident, graduated high school from the Bush School in Seattle. She received her bachelor of science in biology with honors from Lewis & Clark College in Portland, Ore., then continued her education with professional training and a doctorate in veterinary medicine from the University of Wisconsin in Madison, Wisc. Dr. Rich is currently in her second year of a three-year veterinary dermatology residency training program with David Duclos, DVM, DACVD, at the Animal Skin and Allergy Clinic in Lynnwood, Wash. She lives in Edmonds, Wash., with her husband, Michael, Rosy their feisty pug, Milo a rambunctious golden retriever, and Jasper their leopard gecko.
- Little, Peter R., et al. “A Blinded, Randomized Clinical Trial Comparing the Efficacy and Safety of Oclacitinib and Ciclosporin for the Control of Atopic Dermatitis in Client-Owned Dogs.” Veterinary Dermatology, vol. 26, no. 1, 2014, pp. 23-30.
- Munday, John S., et al. “Papillomaviruses in Dogs and Cats.” The Veterinary Journal, vol. 225, 2017, pp. 23–31.
- Richman, Austin W., et al. “Persistent Papilloma Treated with Cryotherapy in Three Dogs.” Veterinary Dermatology, vol. 28, no. 1, 2017, pp. 625–628.
This Education Center article was underwritten by Aesculight of Bothell, Wash., manufacturer of the only American-made CO2 laser.