Canine chronic ulcerative stomatitis (CCUS) is a spontaneously occurring, painful, and often debilitating condition of the oral cavity, with a suspected immune-mediated component. The response to pharmacological treatment is generally poor, thus the need to identify more effective medical therapies for this condition. This article describes a prospective clinical trial that was designed to evaluate the efficiency of a combination of cyclosporine and metronidazole in managing CCUS. The hypothesis was that a combination of cyclosporine and metronidazole would effectively minimize clinical signs associated with CCUS. Ten client-owned dogs with a biopsy-confirmed diagnosis consistent with CCUS were prescribed cyclosporine (5 mg/kg) for 1 week, followed by the addition of metronidazole (15-20 mg/kg), both administered orally once daily. The cyclosporine dosage interval was lengthened over time. Dogs were observed for a 6-month period and evaluated using a 32-point Canine Ulcerative Stomatitis Disease Activity Index (CUSDAI). Regular cyclosporine therapeutic drug monitoring was also conducted by the measurement of whole blood cyclosporine levels and the pharmacodynamic assessment of the T-cell expression of IL-2. The results demonstrated that a combination of cyclosporine and metronidazole was effective in minimizing the clinical signs of CCUS and in reducing CUSDAI scores. Neither blood cyclosporine levels nor the T-cell expression of IL-2 predicted improvement in clinical signs and CUSDAI scores, although there was a correlation between blood drug concentrations and the suppression of T-cell IL-2 expression. The evaluation of clinical signs and CUSDAI scores appears to be the most effective means of assessing response to therapy, and therapeutic drug level monitoring does not appear to be routinely indicated.
Keywords: CCUS; CsA; canine chronic ulcerative stomatitis; cyclosporine; cyclosporine pharmacodynamic assay; metronidazole; oral cavity; whole blood cyclosporine levels.