Opportunistic Invasive Cutaneous Fungal Infections Associated with Administration of Cyclosporine to Dogs with Immune-mediated Disease.

BACKGROUND: Opportunistic invasive fungal infections (OIFIs) occur in dogs administered immunosuppressive medications. However, the epidemiology of OIFIs among dogs undergoing immunosuppressive treatment is poorly understood. The aims of this study were to (1) estimate the incidence of OIFIs among dogs diagnosed with certain immune-mediated diseases and treated with immunosuppressive drugs, and (2) determine if administration of particular drug(s) was a risk factor for OIFIs. HYPOTHESIS: Dogs receiving cyclosporine treatment (alone or as part of a multidrug protocol) are at higher risk of developing OIFIs. ANIMALS: One hundred and thirteen client-owned dogs diagnosed with select immune-mediated diseases: 42 with IMHA, 29 with ITP, 34 with IMPA, and 8 with Evans syndrome. METHODS: Retrospective cohort study. Medical records of dogs presenting to the Texas A&M University, Veterinary Medical Teaching Hospital between January 2008 and December 2015, and treated for 1 or more of IMHA, IMPA, ITP, or Evans syndrome were retrospectively reviewed. Dogs that did not develop an OIFI were excluded if they died, were euthanized, or were lost to follow-up within 120 days of initiation of immunosuppressive treatment. RESULTS: Fifteen dogs of 113 (13%) were diagnosed with an OIFI based on 1 or more of cytology, culture, or histopathology. The odds of developing an OIFI were greater among dogs that were treated with cyclosporine (OR = 7.1, P = 0.017; 95% CI, 1.5-34.4) and among male dogs (OR = 5.1, P = 0.018; 95% CI, 1.4-17.9). CONCLUSIONS AND CLINICAL IMPORTANCE: OIFIs were significantly more likely in male dogs and those receiving cyclosporine. It is important to consider OIFIs as a potential complication of immunosuppressive treatment, particularly cyclosporine.

Utility of endoscopic biopsies of the duodenum and ileum for diagnosis of inflammatory bowel disease and small cell lymphoma in cats.

BACKGROUND: Endoscopic duodenal biopsies are relatively convenient, minimally invasive tests for infiltrative intestinal disorders of cats. Ileal endoscopic biopsies might not be performed because of technical difficulty and effort required to prepare the colon. It is not known whether or not histopathology of feline duodenal and ileal biopsies for detection of inflammatory bowel disease (IBD) and small cell lymphoma (SC-LSA) provides comparable results. OBJECTIVES: To evaluate the agreement between endoscopic biopsies of duodenum and ileum in cats with IBD and SC-LSA. ANIMALS: Seventy client-owned cats with gastrointestinal disease and adequate duodenal and ileal tissue biopsies obtained endoscopically. METHODS: Retrospective study: Search of medical records of cats with enteropathy and endoscopy. Samples were blinded and re-evaluated by single pathologist (JM) for quality, number of biopsies, and diagnosis according to WSAVA standards. Agreement of IBD and SC-LSA diagnoses among biopsy sites assessed using Cohen's Kappa. RESULTS: Eighteen of 70 cats (26%) were diagnosed with SC-LSA in duodenum, ileum, or both. Of these 18 cats, 7 (39%) were diagnosed with only duodenal SC-LSA, 8 (44%) were diagnosed with only ileal SC-LSA, and 3 (17%) had SC-LSA in both duodenum and ileum. There was poor agreement on diagnosis between duodenal and ileal biopsies (kappa = 0.23). CONCLUSIONS AND CLINICAL IMPORTANCE: Although review by a single pathologist remains a limitation of this study, results suggest that there is a population of cats in which diagnosis of SC-LSA can be found only by evaluation of ileal biopsies. Clinicians should consider performing both upper and lower GI endoscopic biopsies in cats with infiltrative small bowel disease.

Gastritis in Alaskan racing sled dogs.

Alaskan racing sled dogs are a well-established model of exercise-induced gastric disease. The aim of this study was to define the temporal development of microscopical gastric lesions during long distance racing. Two groups of dogs were examined: group I comprised conditioned dogs that were exercising and group II were conditioned dogs not exercising. The gastric mucosa was examined endoscopically and sampled for routine histopathology and microscopical scoring, immunohistochemistry (IHC) and detection of apoptotic epithelial cells. Overall, group I dogs exhibited more significant epithelial lesions, including ulcers, compared with dogs in group II. Group II dogs exhibited the most severe mucosal inflammatory infiltrates. Although the intensity of inflammation differed, the nature of the inflammation was similar between groups, consisting of diffuse lymphocytic infiltration and a unique interface-type infiltrate that obscured the basement membrane zone and was accompanied by intraepithelial infiltration of lymphocytes. IHC confirmed the presence of CD3(+) T and CD79(+) B lymphocytes within the mucosal infiltrates; however, most of the intraepithelial and interface infiltrates were CD3(+) T cells. Spiral-shaped bacterial organisms were seen in the gastric tissues; however, their presence did not correlate with either the severity of epithelial lesions, inflammation or the pattern of interface inflammation. The number of apoptotic epithelial cells was widely variable and not significantly different between groups. These findings confirm previous observations that gastric ulcers develop in conditioned dogs under racing stress. The unique nature of the interface-type gastric inflammation is similar to that of human lymphocytic gastritis and may suggest an immune-mediated mechanism for the changes seen in Alaskan racing sled dogs.

Efficacy of omeprazole versus high-dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs.

BACKGROUND: Omeprazole and famotidine both reduce severity of exercise-induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. HYPOTHESIS: Famotidine is more efficacious than no treatment in reducing severity of exercise-induced gastritis; and high-dose famotidine is more efficacious than omeprazole in reducing severity of exercise-induced gastritis. ANIMALS: Experiment 1: Randomized placebo-controlled study, 36 sled dogs (3-8 years); Experiment 2: Randomized positive-control study, 52 sled dogs (2-8 years). METHODS: Experiment 1: Equal numbers of dogs randomly assigned to famotidine (20 mg q24h) or no treatment groups. Gastroscopy was performed 24 hours after the dogs ran 330 miles. Mucosal appearance was blindly scored by previously described scoring system. Experiment 2: Equal numbers of dogs randomly assigned to omeprazole (20 mg q24h) or high-dose famotidine (40 mg q12h) groups. Gastroscopy was performed 48 hours before and 24 hours after the dogs ran 300 miles. Mucosal appearance was blindly scored by previously described scoring system. RESULTS: Famotidine reduced the prevalence of clinically relevant, exercise-induced gastric lesions compared with no treatment (7/16 versus 11/16, P = .031). Compared with high-dose famotidine, omeprazole significantly decreased the severity (0.4 versus 1.2, P = .0002) and prevalence (2/23 versus 7/21, P = .049) of gastric lesions. CONCLUSIONS AND CLINICAL RELEVANCE: Although famotidine provides some benefit in the prevention of exercise-induced gastric lesions, omeprazole is superior to famotidine in preventing gastritis in dogs running 300 miles. Routine administration of omeprazole is recommended to prevent stress-associated gastric disease in exercising and racing Alaskan sled dogs.

Effect of tissue processing on assessment of endoscopic intestinal biopsies in dogs and cats.

BACKGROUND: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. HYPOTHESIS: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. ANIMALS: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. METHODS: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while kappa statistics determined agreement between pathologists on histologic lesions. RESULTS: There was poor agreement (kappa = -0.013 to 0.3) between pathologists, and institution of origin of slides had effect (kappa = 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum kappa = 0.69 using 4-point scale versus maximum kappa = 1.0 using 2-point scale). Significant association (P = .019- .04; 95% OR = 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.

Comparison of histopathologic findings in biopsies from the duodenum and ileum of dogs with enteropathy.

BACKGROUND: In the investigations of dogs with chronic small intestinal diarrhea collection of ileal biopsies lengthens procedural time and has been of uncertain value. OBJECTIVES: To evaluate whether there was agreement between histologic changes present in samples of duodenal and ileal mucosa, and hence to provide initial information in the process of determining whether collection of ileal biopsies is clinically justified. ANIMALS: 40 dogs with chronic small and large intestinal diarrhea from which endoscopic (in 30 cases) or surgical (in 10 cases) duodenal and ileal biopsies had been collected. METHODS: Samples were reviewed concurrently by two observers (MJD and MDW) using the scoring system developed by the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group. Comparisons were made by kappa analysis. RESULTS: Microscopic pathology was observed in 30 cases. Only eight out of this 30 (27%) had the same histopathologic diagnosis in both the duodenum and the ileum. This dropped to 3 out of 30 (10%) if different disease severity was also considered as disagreement. Microscopic pathology would have been found in 60% and 80% of the 30 cases, if only duodenal or ileal biopsies respectively, had been available. CONCLUSIONS AND CLINICAL IMPORTANCE: There was poor agreement between histopathological findings from duodenal versus ileal biopsies with abnormalities sometimes being more readily detected in the ileum. Routine collection of ileal plus duodenal samples appears warranted when concurrent small and large intestinal diarrhea is present.

Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats.

BACKGROUND: The quality of histopathology slides of endoscopic biopsies from different laboratories varies, but the effect of biopsy quality on outcome is unknown. HYPOTHESIS: The ability to demonstrate a histologic lesion in the stomach or duodenum of a dog or cat is affected by the quality of endoscopic biopsy samples submitted. More endoscopic samples are needed to find a lesion in poor-quality tissue specimens. ANIMALS: Tissues from 99 dogs and 51 cats were examined as clinical cases at 8 veterinary institutions or practices in 5 countries. METHODS: Histopathology slides from sequential cases that underwent endoscopic biopsy were submitted by participating institutions. Quality of the histologic section of tissue (inadequate, marginal, adequate), type of lesion (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity of different quality tissue samples for finding different lesions was determined. RESULTS: Fewer samples were required from dogs for diagnosis as the quality of the sample improved from inadequate to marginal to adequate. Duodenal lesions in cats displayed the same trend except for moderate duodenal infiltrates for which quality of tissue sample made no difference. Gastric lesions in dogs and mild gastric lesions in cats had the same trend, whereas the number of tissue samples needed to diagnose moderately severe gastric lesions in cats was not affected by the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE: The quality of endoscopically obtained tissue samples has a profound effect on their sensitivity for identifying certain lesions, and there are differences between biopsies of canine and feline tissues.

Prevalence of gastric lesions in racing Alaskan sled dogs.

Human and equine athletes are reported to have a high prevalence of gastric disease, and anecdotal evidence suggests a similar phenomenon applies to racing sled dogs. To investigate the prevalence of gastric disease in racing sled dogs, we conducted 2 gastroscopy studies on dogs competing in the annual Iditarod Sled Dog Race. A pilot study of dogs that were either dropped from the 2000 Iditarod Sled Dog Race because of illness or that finished the race indicated that, approximately 5 days after competing, 10 of 28 dogs (35%) had endoscopic evidence of gastric ulceration, erosion, or hemorrhage. The next year, an endoscopic study of 73 dogs participating in the 2001 Iditarod race was performed in order to evaluate a larger population of dogs. Data from 70 of these dogs could be used; 34 (48.5%) had ulceration, erosion, gastric hemorrhage, or some combination of these findings. When this group of 70 dogs was compared retrospectively to a control group of 87 dogs presented to the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital, the Iditarod sled dogs had a significantly higher prevalence (P = .049) of gastric lesions. These findings suggest that, similar to athletes of other species, elite canine athletes have an increased prevalence of gastric disease compared to the canine population at large.

Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs.

Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastric severity score compared to placebo (omeprazole: 0.65 +/- 0.17, placebo: 1.09 +/- 0.18; P = .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P = .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes.

Colonoscopy, proctoscopy, and ileoscopy.

Colonoscopy and proctoscopy are primarily performed on dogs and cats with signs of chronic large bowel or rectal disease, and ileoscopy is typically performed in patients with signs of either large or small bowel disease. These techniques should not be used indiscriminately but only on animals that have a reasonable chance to benefit from their use. Even then, the techniques must be performed carefully so that the results are meaningful instead of misleading. We first consider what does and what does not constitute a reasonable indication for endoscopic examination of the lower intestines. After that, we turn to the specific techniques involved.

Quality of tissue specimens obtained endoscopically from the duodenum of dogs and cats.

OBJECTIVE: To evaluate quality of duodenal tissue specimens obtained endoscopically from dogs and cats and submitted to 1 of 2 diagnostic laboratories for evaluation. DESIGN: Case series. SAMPLE POPULATION: Slides from 50 consecutive canine and 50 consecutive feline endoscopically obtained duodenal tissue specimens submitted to laboratory 1 and 49 consecutive canine and 46 consecutive feline specimens submitted to laboratory 2. PROCEDURE: Slides were examined independently by 3 investigators, and each tissue piece on each slide was classified as clearly inadequate, questionable, or clearly adequate on the basis of 4 criteria. An overall score was then assigned to the slide. RESULTS: Slides from laboratory 1 were more likely to be scored as clearly adequate and less likely to be scored as clearly inadequate than slides from laboratory 2. Clearly adequate slides from laboratory 1 had a higher number of clearly adequate pieces of tissue than did clearly adequate slides from laboratory 2. Slides scored as clearly adequate had a higher number of individual tissue pieces than did slides scored as clearly inadequate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the quality of endoscopically obtained duodenal tissue specimens submitted to laboratories can vary, possibly because of differences in experience of individuals collecting biopsy specimens. Results suggest that at least 8 individual tissue pieces should be submitted when performing endoscopic biopsy of the duodenum in dogs and cats.

Effects of dietary fructooligosaccharide on selected bacterial populations in feces of dogs.

OBJECTIVE: To evaluate fecal concentrations of selected genera of colonic bacteria in healthy dogs, and to investigate effects of dietary fructooligosaccharides (FOS) on those bacterial populations. ANIMALS: 6 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to 2 groups of 3 and fed an unsupplemented diet for 370 days. After 88 days, fecal samples were collected. Another fecal sample was collected from each dog 282 days later. Group A then received a diet supplemented with FOS, and group B continued to receive the unsupplemented diet. Twenty-eight to 29 days later, fecal samples were collected. Diets were switched between groups, and fecal samples were collected 31 and 87 days later. Concentrations of Bifidobacterium spp, Lactobacillus spp, Clostridium spp, Bacteroides spp, and Escherichia coli in freshly collected feces were determined. Effects of diet and time on bacterial concentrations were compared between groups. RESULTS: Bifidobacterium spp and Lactobacillus spp were inconsistently isolated from feces of dogs fed either diet. Sequence of diet significantly affected number of Bacteroides spp subsequently isolated from feces, but diet had no effect on numbers of Clostridium spp or E coli. CONCLUSIONS AND CLINICAL RELEVANCE: Some genera of bacteria (eg, Bifidobacterium) believed to be common components of colonic microflora may be only sporadically isolated from feces of healthy dogs. This deviation from expected fecal flora may have implications for the effectiveness of supplementing diets with prebiotics.

Intestinal crypt lesions associated with protein-losing enteropathy in the dog.

Six dogs were diagnosed with protein losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa.

Endoscopic examination of the choanae in dogs and cats: 118 cases (1988-1998).

OBJECTIVE: To determine whether endoscopic examination of the choanae resulted in diagnosis of various diseases in dogs and cats with signs of respiratory tract disease. DESIGN: Retrospective study. ANIMALS: 91 dogs and 27 cats that had endoscopic examination of the choanae. PROCEDURE: Medical records were reviewed for endoscopy findings and results of examination of biopsy or cytologic specimens. RESULTS: 34 animals had neoplasia in the choanal region; in 26 animals, diagnosis was confirmed by evaluation of specimens obtained by endoscopy. Five dogs with neoplasia had an erroneous diagnosis of rhinitis made on the basis of evaluation of specimens obtained by endoscopy. Six dogs and 2 cats had foreign objects in the choanae; 7 foreign objects were removed endoscopically, whereas 1 required nasal flushing. Results of endoscopy and biopsy of the choanae provided diagnosis of cryptococcosis and aspergillosis, but did not aid in the diagnosis of pythiosis or nasal mites. CONCLUSIONS AND CLINICAL RELEVANCE: Endoscopic examination of the choanae may assist in rapid diagnosis of nasal neoplasms, foreign objects, and certain infectious organisms.

Hypercalcemia associated with granulomatous disease in a cat.

A 6-year-old cat was examined because of recurrence of a draining mass involving skin and subcutaneous tissues of the caudoventral aspect of the abdomen. Previous treatment included administration of antimicrobial drugs and corticosteroids and surgical excision. Atypical mycobacteria were seen during cytologic examination of biopsy specimens of the mass; Nocardia sp was cultured. While hospitalized, the cat developed hypercalcemia and was found to have high serum calcitriol concentrations. Treatment consisted of administration of ciprofloxacin and trimethoprim-sulfadiazine because of the infection and administration of sodium chloride solution, furosemide, and calcitonin because of the hypercalcemia. The cat recovered.

Cryptosporidiosis, coccidiosis, and total colonic mucosal collapse in an immunosuppressed puppy.

An eight-week-old puppy with chronic diarrhea was diagnosed with simultaneous opportunistic pathogens (i.e., cryptosporidiosis, coccidiosis) and total colonic mucosal collapse. Lack of lymphoid follicles in the spleen and lymph nodes suggested a primary underlying immunosuppression that most likely permitted infection with these pathogens. Intensive antibiotic therapy was most likely responsible for the severe colonic lesion, and bismuth subsalicylate administration in this severely dehydrated puppy may have contributed to renal failure as the ultimate cause of death.

Fine-needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease.

Four cats are reported in which cytology smears obtained by ultrasound-guided fine needle aspiration of the liver were interpreted as indicative of hepatic lipidosis. However, histopathology of hepatic tissue samples obtained with Tru-Cut-like needles or wedge biopsy revealed that the cats had inflammatory or neoplastic hepatic disease causing their clinical signs. Fine needle aspiration and cytology may not detect infiltrative lesions, particularly those that are nodular, multifocal, or localised around the portal regions. Fine needle aspirate cytology is a useful diagnostic procedure with many advantages, but care must be taken to avoid diagnosing hepatic lipidosis as the cause of illness when an infiltrative lesion is responsible.

Feline inflammatory bowel disease: a review.

Inflammatory bowel disease (IBD), while a popular diagnosis, may not occur as commonly as it is diagnosed. It is a diagnosis of exclusion, meaning that it is important to eliminate diseases that mimick it. Dietary intolerance or allergy in particular, can have the same clinical and histologic appearance as IBD. Likewise, well-differentiated alimentary lymphosarcoma can also be confused with it. Intestinal biopsies are useful, but must be taken carefully and then evaluated by someone with interest and expertise in alimentary tract pathology. Therefore, it behoves the clinician to carefully consider the diagnosis instead of starting multiple drug therapy in a cavalier fashion. Well constructed dietary therapy can often be beneficial for both dietary problems and IBD.