Histopathologic Variation between Liver Lobes in Dogs

Background

Biopsy of the liver evaluates a small portion of tissue, with inferences made to the entire organ. The method and number of biopsies obtained are tempered by consideration of the risks and benefits. Recommendations often include biopsy of more than one liver lobe, although the consistency of histopathology among lobes in dogs is unknown.

Hypothesis/Objectives

To describe the distribution of histopathologic abnormalities between liver lobes. We hypothesized that discordant results would be evenly distributed among all liver lobes.

Animals

Seventy dogs undergoing necropsy.

Methods

Prospective study. Liver samples were obtained from all lobes. A primary diagnosis was assigned to each liver sample based on the predominant histopathologic abnormality.

Results

In this population of dogs, biopsy of at least 2 liver lobes identified the predominant histologic abnormality in 98.6% of the cases. Ten (14%) of the dogs had ≤3 lobes in agreement and could not be assigned a predominant diagnosis. The same diagnosis was present in 6/6 lobes in 39 (56.5%) dogs, 5/6 lobes in 10 (14.5%) dogs, 4/6 lobes in 10 (14.5%) dogs, 3/6 lobes in 7 (10.1%) dogs, and 2/6 in 3 (4.3%) dogs. The number of discordant results did not differ between the liver lobes.

Conclusion and Clinical Importance

The likelihood of obtaining a sample that is reflective of the predominant histologic abnormality in the liver is increased when multiple liver lobes are biopsied.     

Validation of an Ultrasound Imaging Technique of the Tympanic Bullae for the Diagnosis of Otitis Media in Calves

Background

Otitis media is a common disease in calves that can be subclinical, making antemortem on‐farm diagnosis challenging.

Objectives

To evaluate the sensitivity and specificity of ultrasonography of tympanic bullae for the diagnosis of clinical and subclinical otitis media and to evaluate the reproducibility of the technique.

Animals

Forty calves 19–50 days of age were selected from a veal calf farm.

Methods

Prospective study. Ultrasonography was first performed on the farm by ultrasonographer A (US A). Ultrasonography was repeated by ultrasonographer A (US A'') and another ultrasonographer (US B) at the Centre Hospitalier Universitaire Vétérinaire. Images were later reread by both examiners and a diagnosis was recorded. The calves were euthanized and submitted for necropsy, and histopathologic diagnosis was used as the gold standard.

Results

Forty‐five bullae were affected by otitis media and 35 bullae were normal. Sensitivity and specificity of the ultrasound technique ranged from 32 to 63% and 84 to 100%, respectively, depending on the examiner and classification of suspicious ultrasonography results. Kappa analysis to evaluate interobserver agreement between A'' and B yielded a к value of 0.53. Agreement within the same examiner (A versus A'') yielded a к value of 0.48, and real‐time ultrasound versus rereading of recorded images for A'' and B yielded к values of 0.58 and 0.75, respectively.

Conclusions

Sensitivity and specificity of the ultrasound imaging technique are, respectively, low and high for diagnosis of clinical and subclinical otitis media in calves, with moderate reproducibility.     

Phenotypic Characterization of Canine Intestinal Intraepithelial Lymphocytes in Dogs with Inflammatory Bowel Disease

Background

Many dogs suffering from inflammatory bowel disease (IBD) are presented to veterinary clinics. These patients are diagnosed based on a history of chronic gastrointestinal signs and biopsy‐confirmed histopathologic intestinal inflammation. Intestinal intraepithelial lymphocytes (IEL) are part of the first line of defense in the gastrointestinal immune system. Alterations in IEL subsets may play a role in the pathogenesis of IBD.

Hypothesis

The aim of this study was to characterize the phenotypes of IEL in dogs with IBD compared with healthy control dogs.

Animals

Intestinal intraepithelial lymphocytes subpopulations of control dogs (n = 5) obtained from endoscopic biopsies (EB) were compared to those obtained from full thickness biopsies (FTB) on the same day. In addition, the phenotypes of IEL from FTB of control dogs (n = 10) were compared with EB of IBD dogs (n = 10). Each participant was scored clinically using the canine inflammatory bowel disease activity index (CIBDAI), and all samples were graded histopathologically. Three‐color flow cytometry of isolated IEL was performed using monoclonal antibodies against T‐ and B‐lymphocyte subpopulations.

Results

No significant differences in the composition of IEL subpopulations were found in control dogs based on method of biopsy. The IBD dogs had significantly higher CIBDAI and histopathologic scores compared with control dogs and their IEL contained a significantly higher frequency TCRγδ T‐cells.

Conclusions and Clinical Importance

Endoscopic biopsies provide suitable samples for 3‐color flow cytometry when studying canine intestinal IEL and IBD patients show significant changes of major T‐cell subsets compared to healthy control dogs.     

Assessment of the Efficacy and Potential Complications of Transjugular Liver Biopsy in Canine Cadavers

Background

Transjugular liver biopsy (TJLB) is used in humans at risk of bleeding. There are no reports of its use in veterinary medicine.

Objective

To assess the efficacy and potential complications of TJLB in canine cadavers, and compare with samples obtained via needle liver biopsy (NLB) and surgical liver biopsy (SLB).

Animals

Twenty‐five medium and large breed canine cadavers.

Methods

Prospective study. TJLBs were procured through the right jugular vein. After biopsy, intravenous contrast and gross inspection were used to assess the biopsy site. Minor and major complications were recorded. NLBs and SLBs were then obtained. Histopathology was performed, and TJLB and NLB were compared for number of complete portal tracts (CPTs), length, and fragmentation. Pathologic process and autolysis were assessed in all samples.

Results

All TJLBs yielded liver tissue. The proportion of minor complications was 12/25 (48%), and major complications 16/25 (64%); 13/16 (81%) of the major complications were liver capsule perforation. In 21/25 (84%), the histopathology in the SLB was reflected in the TJLBs. For cases with minimal autolysis, median number of CPTs in TJLBs was 7.5, compared with 4 in NLBs (P = .018). Median length of TJLB specimen was 28 mm compared to 22 mm in NLBs (P = .007). Fragmentation rate was median of 1.25 for TJLB compared to 1.50 in NLBs (P = .11).

Conclusions and Clinical Importance

TJLB is technically feasible and achieves comparable results to NLB and SLB. The number of complications, in particular liver capsule perforation, was greater than expected. Further studies are indicated before clinical use is recommended.     

Markers of Angiogenesis Associated with Surgical Attenuation of Congenital Portosystemic Shunts in Dogs

Background

Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected.

Hypothesis

That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration.

Animals

Client‐owned dogs with CPSS undergoing surgical treatment. Forty‐nine dogs were included in the gene expression data and 35 in the serum VEGF data.

Materials and Methods

Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow‐up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05).

Results

There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation.

Conclusions and Clinical Importance

These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively.     

Clinical,Magnetic Resonance Imaging,and Histopathologic Findings in 6 Dogs with Surgically resected Extraparenchymal Spinal Cord Hematomas

Background

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine.

Objectives

To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology.

Animals

Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause.

Methods

Multi‐institutional retrospective study.

Results

Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2‐weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow‐up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency.

Conclusions and Clinical Importance

Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases.     

Echocardiographic Findings in 11 Cats with Acromegaly

Background

Information regarding cardiac changes in domestic cats with acromegaly is limited.

Hypothesis/Objectives

The objective of this study was to describe the echocardiographic findings in cats with acromegaly.

Animals

Eighteen cats diagnosed with acromegaly at Colorado State University between 2008 and 2012. Of these 18 cats, 11 had echocardiography performed.

Methods

A retrospective review of medical records was made to identify cats with acromegaly that also had echocardiography performed.

Results

Of the 11 cats identified, 7 had left ventricular concentric hypertrophy, 6 had left atrial enlargement, and 7 had evidence of abnormal diastolic function. All 11 cats had evidence of structural or functional cardiac disease.

Conclusions and Clinical Importance

Cardiovascular abnormalities frequently are present in cats with acromegaly, and a complete cardiac evaluation should be considered in these patients.     

Investigation of Single and Paired Measurements of Adrenocorticotropic Hormone for the Diagnosis of Pituitary Pars Intermedia Dysfunction in Horses

Background

Paired measurement of ACTH concentration may be more reliable than a single measurement.

Hypothesis/Objectives

To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement.

Animals

Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars intermedia was performed in 67 of the untreated horses.

Methods

Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard.

Results

Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively.

Conclusions and Clinical Importance

Paired measurement of ACTH concentration offers no advantage over a single measurement.     

Endoscopically Visualized Lesions,Histologic Findings,and Bacterial Invasion in the Gastrointestinal Mucosa of Dogs with Acute Hemorrhagic Diarrhea Syndrome

Background

Etiology of hemorrhagic gastroenteritis (HGE) syndrome in dogs is unknown and histopathologic and microbial investigations have only been performed post mortem.

Objective

To identify characteristic intra vitam endoscopic and histologic mucosal lesions, as well as bacterial species, within the mucosa of dogs with HGE.

Animals

Ten dogs diagnosed with HGE were included. Eleven dogs with gastroduodenoscopy and different intestinal diseases were used as controls for microbial changes. Dogs pretreated with antibiotics or diagnosed with any disease known to cause bloody diarrhea were excluded from the study.

Methods

In this prospective study, gastrointestinal biopsies were collected from 10 dogs with HGE. Endoscopic and histologic changes were assessed according to WSAVA guidelines. Biopsies from the stomach, duodenum, ileum, and colon were investigated by histology and by immunohistochemistry for the presence of Clostridium spp. and parvovirus. The first duodenal biopsy taken with a sterile forceps was submitted for bacterial culture.

Results

Acute mucosal lesions were only found in the intestines, not in the stomach. Clostridium spp., identified as Clostridium perfringens in 6/9 cases, were detected on the small intestinal mucosa in all dogs with HGE, either by culture or immunohistopathology. In the control group, C. perfringens could only be cultured in one of 11 dogs.

Conclusions and Clinical Importance

The results of this study demonstrate an apparent association between C. perfringens and the occurrence of acute hemorrhagic diarrhea. The term “HGE,” which implies the involvement of the stomach, should be renamed as “acute hemorrhagic diarrhea syndrome.”     

Change in β‐Catenin Localization Suggests Involvement of the Canonical Wnt Pathway in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease with high prevalence in the Boxer dog population. It is characterized by replacement of the myocardium with fatty or fibro‐fatty tissue. Several mechanisms for the development of ARVC have been suggested, including dysfunction of the canonical Wnt pathway, which is linked to many cellular functions, including growth and differentiation of adipocytes.

Hypothesis

Wnt pathway dysfunction is involved in the development of ARVC in the Boxer as evidenced by mislocalization of β‐catenin, an integral Wnt pathway modulator, and striatin, a known Wnt pathway component.

Animals

Five dogs without ARVC and 15 Boxers with ARVC were identified by 24‐hour Holter monitoring and histopathologic examination of the heart.

Methods

Right ventricular samples were collected and examined using confocal microscopy, Western blots, and quantitative (q) PCR.

Results

Confocal microscopy indicated that β‐catenin localized at sites of cell‐to‐cell apposition, and striatin localized in a diffuse intracellular pattern in hearts without ARVC. In hearts affected with ARVC, both β‐catenin and striatin were colocalized with the endoplasmic reticulum (ER) marker calreticulin. Western blots indentified a 50% increase in the amount of β‐catenin in ARVC samples. No change in β catenin mRNA was detected using qPCR.

Conclusions

Our data suggest that trafficking of Wnt pathway proteins from the ER to their proper location within the cell is inhibited in Boxers with ARVC. These results suggest that disturbances in the Wnt pathway may play a role in the development of ARVC in the Boxer.     

Concurrent Diseases and Conditions in Cats with Renal Infarcts

Background

Renal infarcts identified without definitive association with any specific disease process.

Objective

Determine diseases associated with diagnosis of renal infarcts in cats diagnosed by sonography or necropsy.

Animals

600 cats underwent abdominal ultrasonography, necropsy, or both at a veterinary medical teaching hospital.

Methods

Information obtained from electronic medical records. Cats classified as having renal infarct present based on results of sonographic evaluation or necropsy. Time‐matched case‐controls selected from cats that underwent the next scheduled diagnostic procedure.

Results

309 of 600 cats having diagnosis of renal infarct and 291 time‐matched controls. Cats 7–14 years old were 1.6 times (odds ratio, 95% CI: 1.03–2.05, P = .03) more likely to have renal infarct than younger cats but no more likely to have renal infarct than older cats (1.4, 0.89–2.25, P = .14). All P = .14 are statistically significant. Cats with renal infarcts were 4.5 times (odds ratio, 95% CI: 2.63–7.68, P < .001) more likely to have HCM compared to cats without renal infarcts. Cats with renal infarcts were 0.7 times (odds ratio, 95% CI: 0.51–0.99, P = .046) less likely to have diagnosis of neoplasia compared to cats without renal infarcts. Cats with diagnosis of hyperthyroidism did not have significant association with having renal infarct. Cats with renal infarcts were 8 times (odds ratio, 95% CI: 2.55–25.40, P ≤ .001) more likely to have diagnosis of distal aortic thromboembolism than cats without renal infarcts.

Conclusions and Clinical Importance

Cats with renal infarcts identified on antemortem examination should be screened for occult cardiomyopathy.     

Histiocytic Sarcoma with Central Nervous System Involvement in Dogs: 19 Cases (2006–2012)

Background

Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1–3 animals.

Objective

The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement.

Animals

Nineteen dogs with HS examined at veterinary referral hospitals.

Methods

Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis.

Results

Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days.

Conclusions and Clinical Importance

Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.     

Use of Fourier‐Transform Infrared Spectroscopy to Quantify Immunoglobulin G Concentrations in Alpaca Serum

Background

Rapid, economical, and quantitative assays for measurement of camelid serum immunoglobulin G (IgG) are limited. In camelids, failure of transfer of maternal immunoglobulins has a reported prevalence of up to 20.5%. An accurate method for quantifying serum IgG concentrations is required.

Objective

To develop an infrared spectroscopy‐based assay for measurement of alpaca serum IgG and compare its performance to the reference standard radial immunodiffusion (RID) assay.

Animals

One hundred and seventy‐five privately owned, healthy alpacas.

Methods

Eighty‐two serum samples were collected as convenience samples during routine herd visits whereas 93 samples were recruited from a separate study. Serum IgG concentrations were determined by RID assays and midinfrared spectra were collected for each sample. Fifty samples were set aside as the test set and the remaining 125 training samples were employed to build a calibration model using partial least squares (PLS) regression with Monte Carlo cross validation to determine the optimum number of PLS factors. The predictive performance of the calibration model was evaluated by the test set.

Results

Correlation coefficients for the IR‐based assay were 0.93 and 0.87, respectively, for the entire data set and test set. Sensitivity in the diagnosis of failure of transfer of passive immunity (FTPI) ([IgG] <1,000 mg/dL) was 71.4% and specificity was 100% for the IR‐based method (test set) as gauged relative to the RID reference method assay.

Conclusions and Clinical Importance

This study indicated that infrared spectroscopy, in combination with chemometrics, is an effective method for measurement of IgG in alpaca serum.     

Atlanto‐Axial Malformation and Instability in Dogs with Pituitary Dwarfism due to an LHX3 Mutation

Background

Canine pituitary dwarfism or combined pituitary hormone deficiency (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a wide range of clinical manifestations. Some dogs with CPHD have neurological signs that are localized to the cervical spine. In human CPHD, caused by an LHX3 mutation, anatomical abnormalities in the atlanto‐axial (C1‐C2) joint have been described.

Objectives

To evaluate the presence of atlanto‐axial malformations in dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate the degree of similarity between the atlanto‐axial anomalies found in canine and human CPHD patients with an LHX3 mutation.

Animals

Three client‐owned Czechoslovakian wolfdogs and 1 client‐owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological signs indicating a cervical spinal disorder.

Methods

Radiography, computed tomography, and magnetic resonance imaging of the cranial neck and skull, necropsy, and histology.

Results

Diagnostic imaging identified abnormal positioning of the dens axis and incomplete ossification of the suture lines between the ossification centers of the atlas with concurrent atlanto‐axial instability and dynamic compression of the spinal cord by the dens axis. The malformations and aberrant motion at C1–C2 were confirmed at necropsy and histology.

Conclusions and Clinical Importance

The atlanto‐axial abnormalities of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3 mutation. These findings suggest an association between the LHX3 mutation in dogs with CPHD and atlanto‐axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs.     

Comparison between Urine Protein: Creatinine Ratios of Samples Obtained from Dogs in Home and Hospital Settings

Background

The urine protein:creatinine ratio (UPC) is used to quantify urine protein excretion and guide recommendations for monitoring and treatment of proteinuria.

Hypothesis/Objectives

Home urine samples will have lower UPCs than hospital samples. The objectives were to compare UPCs of samples collected in each setting and to determine whether environment of sample collection might affect staging, monitoring or treatment recommendations.

Animals

Twenty‐four client‐owned dogs.

Methods

Prospective, nonmasked study. Clients collected a urine sample from their dog at home and a second sample was collected at the hospital. Dogs receiving corticosteroids or angiotensin‐converting enzyme inhibitors were excluded, as were those with urine samples of inadequate volume, no protein on dipstick analysis, or active urine sediment. Samples were refrigerated after collection, dipstick and sediment evaluations were completed and each sample was frozen at −80°C within 12 hours. UPCs were performed on frozen samples within 2 months.

Results

From 81 paired samples, 57 were excluded. Of the remaining 24, 12/24 (50%) had higher hospital sample UPCs, 9/24 (38%) had identical UPCs, and 3/24 (12%) had lower hospital UPCs. The UPCs of hospital samples were higher than home samples for the total population (P = .005) and the subset with UPC > 0.5 (P = .001).

Conclusions

Setting and related circumstances of urine collection in dogs is associated with UPC differences; results are usually higher in hospital than in home samples. This difference has the potential to affect clinical interpretation.     

Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review

Background

Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed‐restricted disorder.

Hypothesis/Objectives

Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.

Animals

Four dogs with NME.

Methods

Archives from 3 institutions and from 1 author''s (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.

Results

Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.

Conclusions and Clinical Importance

Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.     

Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

Diagnostic Yield of Cytologic Analysis of Pericardial Effusion in Dogs

Background

Pericardial effusion cytology is believed by many to be of limited value, yet few studies have evaluated its diagnostic utility.

Objectives

To determine the diagnostic utility of cytologic analysis of pericardial effusion in dogs and to determine if consideration of additional data could improve the diagnostic yield.

Animals

Two hundred and fifty‐nine dogs with cytologic analysis of pericardial effusion performed between April 1990 and June 2012.

Methods

Electronic medical records from a university teaching hospital were retrospectively reviewed; signalment, complete blood count, serum biochemistry, cytologic analysis of pericardial effusion, and echocardiographic data were recorded. Cytology was classified as diagnostic (infectious or neoplastic) or nondiagnostic (hemorrhagic or other) and groups were compared with multiple Student''s t‐tests.

Results

Cytology was grouped as nondiagnostic (92.3%) or diagnostic (7.7%) and characterized as hemorrhagic (90%), neoplastic (4.6%), infectious (3.1%), or other (2.3%). Overall cytologic analysis of pericardial effusion diagnostic utility was 7.7% and increased to 20.3% if the effusion hematocrit (HCT) <10%; echocardiographic evidence of a mass did not result in a significant increase in the diagnostic utility.

Conclusions and Clinical Importance

The diagnostic utility of cytologic analysis of canine pericardial effusion is variable depending on the underlying etiology. In this group of dogs, the diagnostic yield of cytologic analysis was greater for pericardial effusion samples in which the HCT was less than 10%.