Prevalence of hepatotoxicity and myelosuppression with alternate day use of azathioprine and glucocorticoids for treatment of dermatological conditions in dogs.

BACKGROUND: The use of azathioprine (AZA) in dogs is limited by the potential for hepatotoxicity and myelosuppression. HYPOTHESIS/OBJECTIVES: To determine the prevalence of AZA-associated hepatotoxicity in dogs with dermatological conditions receiving alternate-day AZA. The hypothesis was that dogs receiving AZA every other day (EOD) would have a lower prevalence of hepatotoxicity compared to published data for dogs receiving daily AZA. A secondary aim was to determine the prevalence of AZA-associated myelosuppression over the same time period and population. ANIMALS: Forty-one client-owned dogs with dermatological conditions treated with AZA EOD and glucocorticoids with clinical and haematological follow-up available for a minimum of two months of AZA therapy. METHODS: Retrospective analysis of data from April 1994 to July 2020. Hepatotoxicity was defined as elevation of alanine aminotransferase (ALT) at least twofold above the reference range. RESULTS: Azathioprine-associated hepatotoxicity was observed in two of 41 dogs (4.9%), with onset at 18 and 40 days, respectively. One dog receiving AZA at 1.9 mg/kg EOD had a fourfold increase in ALT. The other dog (AZA dose 2.3 mg/kg EOD) had a 30-fold increase in ALT. Azathioprine was not associated with thrombocytopenia, anaemia or neutropenia in any dogs. Lymphopenia developed in one dog (2.4%) with onset at 105 days. CONCLUSIONS AND CLINICAL RELEVANCE: Alternate-day AZA administration with tapering glucocorticoids was well-tolerated in dogs with dermatological conditions.

Characterization and quantification of ceramides in the nonlesional skin of canine patients with atopic dermatitis compared with controls.

As in humans, there is mounting evidence in support of an abnormal skin barrier contributing to the pathogenesis of canine atopic dermatitis (AD). Studies in people with AD have associated an abnormal skin barrier with deficiencies in ceramides, which represent important components of the stratum corneum (SC) intercellular lipid lamellae. Therefore, the goal of this study was to determine if the SC of dogs with AD is deficient in ceramides compared to normal dogs. Samples of SC were obtained from nonlesional skin of the caudal abdomen of 14 patients with AD and 14 age-, breed- and sex-matched healthy controls using a cyanoacrylate stripping procedure, and the subclass and relative amount of ceramides were assessed blindly by thin layer chromatography. Paired t-tests using R statistical computer software revealed the percentage amounts of ceramides 1 and 9 were significantly lower in nonlesional skin of AD dogs compared to controls (P= 0.034 and P= 0.047, respectively), and the cholesterol percentage amount was significantly higher in AD dogs than in controls (P= 0.016). Furthermore, the cholesterol/ceramide ratio was significantly higher in the AD group with respect to controls (P= 0.014). These findings suggest that decreased amounts of ceramides in the skin of dogs with AD may be involved in the impaired barrier function of their skin.

Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin-2 in healthy dogs.

There are numerous studies of the pruritus-producing effects of histamine, serotonin, tryptase, substance P and interleukin-2 in humans and mice, but very little reported in dogs even though a common reason dogs are presented to veterinarians is pruritus. The aim of this study was to determine whether substances known to cause pruritus in humans also cause pruritus in dogs. Twenty-five clinically healthy research beagle dogs were included in the study. All dogs first received an intradermal injection of 0.05 mL saline as a control substance and were video-recorded for 20 min before and after the injection. Twenty-four hours later the dogs were randomly divided into five groups of five dogs each and randomly assigned to receive histamine, serotonin, tryptase, substance P or interleukin-2 injected intradermally each at the volume of 0.05 mL. On subsequent days, increasing concentrations of each substance were used. Before (baseline) and after the injection of each concentration of the substances, the dogs were video-recorded for 20 min. The frequency and character of pruritus episodes (scratching, licking, chewing, rubbing or rolling) were noted and these data were used for statistical analysis. The number of pruritus episodes was compared among baseline, saline and the different concentrations of each substance. The results showed that dogs did not have a significant increase in pruritic behaviour above baseline or saline after injection of any of the investigated substances (generalized linear model; P = 0.23).