FIP is caused by infection with a mutant biotype of feline enteric coronavirus (FECV), which can lead to various complex clinical signs.^3-5 FECV infection rates vary significantly across populations, infection occurs in ≈40% of cats worldwide and 90% to 100% of cats in multicat households^3,6; however, only a small percentage (<10%) of cats develop FIP.

The pathogenesis may be difficult to explain to pet owners. In addition to virus exposure, FIP development depends on environmental stressors, genetic predisposition, and random viral mutation. The disease is complex and can be best understood when described as a series of steps^3,4,7:

1. Cats are exposed to FECV, which enters enterocytes using a spike (S) protein gene on the viral surface. Usually, FECV causes self-limiting gastroenteritis that is often undiagnosed. FECV may also spread systemically without causing FIP.⁵
2. In some cats, the S protein gene mutates—the viral 3c gene may also be truncated—causing tropism to change from enterocytes to macrophages/monocytes; this mutated virus is referred to as FIP virus (FIPV). The mutated virus replicates within immune cells and is no longer transmissible through the fecal–oral route.
3. In some cats, a strong cell-mediated immune response can control infection, resulting in viral clearance without clinical disease. If a humoral response predominates, antibodies are ineffective at controlling infection and can lead to immune complex formation, resulting in vasculitis and effusion (ie, wet FIP). In the case of a partial cell-mediated immune response, immune cells are recruited to the site of replication, leading to granuloma formation (ie, dry FIP). The distinction of wet versus dry FIP depends on the ratio of cell-mediated (Th1) and humoral (Th2) responses.⁸
4. Both wet and dry forms result in death if left untreated.

A genetic predisposition to FIP,^9,10 wherein decreased gene heterozygosity may contribute to an altered immune response to FIPV, is likely to occur.² This may explain the apparent predisposition of purebred cats to development of disease.⁹

FIP typically affects cats <3 years of age, with a second smaller peak in prevalence in geriatric cats⁶; however, cats of any age can be affected.

Dry FIP can manifest with organ dysfunction, uveitis, neurologic signs, fever, anemia, and/or lethargy and is caused by granulomas or immune complex deposition. Cats with wet FIP may have ascites or pleural effusion in addition to the aforementioned signs (Figure 1). Clinical presentation can vary from minor to life-threatening and involve almost any organ system.

Many cats with FIP are febrile, but fever can wax and wane. Globulins are classically elevated, often significantly (ie, >7 mg/dL), and albumin is typically normal to low (ie, 2 mg/dL or less). Mild to moderate anemia (ie, hematocrit, 20%-30%), RBC microcytosis, band neutrophilia, and lymphopenia are common; hyperbilirubinemia (as a result of hemolysis) and hyperglobulinemia are also often observed. The albumin:globulin ratio is classically <0.4.^5,11,12 Lymphopenia and hyperbilirubinemia are more prevalent in wet FIP.

Serology for FECV is rarely beneficial,⁶ as serology cannot distinguish FECV and FIPV antibodies, and some cats with FIP may test negative on ELISA,^5,13 which has poor sensitivity for immune complexes. Serology is likely only useful on a population level as a screening tool for coronavirus exposure. No evidence indicates that the viral 7b protein ELISA is superior to other antibody assays.¹⁴

Immunohistochemical detection of coronavirus within lesions is the gold standard for diagnosis of FIP,^5,15 but collection of tissue samples is often impractical because of the need for anesthesia and surgery. Diagnosis is also possible using cytology from ultrasound-guided aspiration of enlarged mesenteric lymph nodes.^5,16

Wet FIP is often readily diagnosed through sampling of effusion, which is typically straw-colored, translucent, and slightly more viscous than water. Fluid generally has low cellularity that consists of mildly degenerate neutrophils and macrophages.

Dry FIP often requires more advanced diagnostics, including tissue aspiration or biopsy. A wide range of diagnostics have been suggested, including routine serum chemistry profiles, diagnostic imaging, measurement of acute-phase proteins, PCR, and cytology. In the absence of immunohistochemistry, combinations of methods are often used to diagnose patients with a high degree of certainty. Consistent nonspecific clinical pathologic findings (Table) should raise suspicion for FIP.⁶

The Rivalta test (Figure 2) is an inexpensive and readily performed in-clinic test with an extremely high negative predictive value for FIP.^5,13 This test is positive in effusions with high protein content (especially acute-phase proteins) and negative in pure transudates. A positive Rivalta test is consistent with FIP in kittens but is less specific in older cats, as septic peritonitis and neoplasia can result in a positive test; however, these conditions can be ruled out via cytology. 

PCR is a valuable modern tool for FIP diagnosis because it allows direct detection of viral RNA; some experts question its use in all cases, but most consider it to be a useful tool. Detection of FECV by PCR in tissue or effusion is consistent with FIP but not definitive, as non-FIP FECV may also be present in the tissue of healthy animals; however, failure to detect FECV can indicate that FIP is unlikely.⁷ Some specific S protein gene mutations are associated with FIP, and PCR tests that target these mutations may have higher specificity^17,18 (ie, FIP diagnosis is more likely if the detected virus has one of these mutations). Although potentially clinically useful, PCR testing is not comprehensive because novel mutations may be missed.^17,19 PCR testing of feces is not useful because fecal coronavirus is not predictive of systemic spread.

PCR sample choice depends on disease presentation; in cases of wet FIP, effusion should be tested, and in cases of dry FIP, peripheral blood, CSF, aqueous humor, lymph nodes, and/or organ aspirates should be tested.^16,20 Test results should be interpreted based on the sample submitted; a positive PCR that identifies specific S protein gene mutations in abdominal effusion likely indicates FIP, but a positive FECV result in peripheral blood is less specific.^19,20 It should be noted that testing is done sequentially. Initially, reverse transcriptase PCR for FECV is performed. When the result is positive, a second PCR should be run to confirm the FECV is FIPV, not FECV, biotype.

Treatment of FIP has traditionally been unrewarding, and management of clinical signs and supportive care to keep cats comfortable have been the mainstays of therapy. Many clinicians administer corticosteroids to reduce the inflammatory response and improve quality of life, but there is no evidence that this extends survival.²¹

The use of immunomodulatory therapy—including immunostimulants, type 1 interferons (IFNs; eg, human IFNα, feline IFNω), and other similar drugs^22,23 intended to bias toward a Th1 response—has been proposed.^21,24 Preliminary data on these approaches have been inconsistent, with some data showing positive effects and others showing no effects.²²

Coronaviral protease inhibitors and nucleoside analogs (eg, GC376 and GS-441524, respectively) represent major breakthroughs in therapy.²⁵ These agents inhibit viral replication and disrupt FIP progression, prolonging patient survival.²⁶ The efficacy and safety of these drugs has been confined to laboratory, clinical, and field studies, but commercialization of GC376 is underway. Although not 100% effective, especially with ocular or CNS involvement, these agents are the most promising therapies to date.^23,25,27 Unfortunately, none are currently commercially available, but the purchase of research-grade drugs online has been widely reported. The legality, ethics, and efficacy of buying and selling these drugs are beyond the scope of this discussion.

Prognosis for FIP is traditionally very poor (ie, <5% 1-year survival rate).⁶ Cats with wet FIP are reported to survive only for weeks¹¹; cats with dry FIP have a longer survival time, but this form is also fatal. Newer antiviral therapies may significantly improve prognosis, and longer-term survival is possible.²⁷

Although a vaccine for FIP is available in some regions, its efficacy is poor and it is not generally recommended. Development of an effective vaccine has been unsuccessful due to the genetic variability of the virus and a lack of sterilizing immunity (ie, vaccination does not prevent infection) and antibody-dependent enhancement (ie, pre-existing antibodies may worsen disease through immune complex formation).²⁸ 

FIP is not directly contagious. FECV is directly contagious and is an enveloped virus with poor environmental survivability; thorough cleaning is needed to disinfect the environment.¹¹ Prevention of coronavirus infection is difficult and can be futile in large groups due to the ubiquity of the virus and number of clinical carriers.

Although diagnosis and treatment of FIP may seem daunting, recent breakthroughs in treatment and understanding have shed light on this previously enigmatic disease. Simple (eg, Rivalta) and more complex (eg, PCR) tests have improved FIP diagnostics, and antiviral drugs show potential for successful therapy.

Newer technology that includes the use of biomarkers and algorithms has been developed to aid in prediction and early disease detection, resulting in earlier treatment and, ultimately, a more favorable patient outcome. Mitzi was one such patient that received testing with this technology and experienced early CKD prediction and a positive outcome as a result.

Mitzi, a 12-year-old, spayed domestic shorthair cat, was presented for a wellness examination. Physical examination revealed diffuse muscle wasting but was otherwise unremarkable. CBC, serum chemistry, thyroid testing, and urinalysis were performed; BUN was normal, but creatinine was in the upper end of the reference range and isosthenuria and proteinuria were evident. A urine protein:creatinine ratio of 0.4 confirmed borderline proteinuria. Noninvasive blood pressure measurement also revealed hypertension (systolic, 160 mm Hg). Urine culture and susceptibility testing was performed and was negative for bacterial growth.

A RenalTech status was reported as a part of Mitzi’s wellness screening to further assess her unique risk for CKD. RenalTech utilizes artificial intelligence and machine learning to measure and compare 6 key values (ie, urine specific gravity, urine protein, urine pH, creatinine, BUN, WBC count), as well as patient age, at 2 different time points (ideally, 6 months apart). The analysis is able to detect subtle changes over time and predicts the development of CKD in a patient within the next 2 years with >95% accuracy.^5,6

Possible statuses generated from the RenalTech algorithm include positive, negative, and inconclusive:

• A positive result indicates that the patient already has CKD or is likely to develop CKD within the next 2 years. If the result is positive, the patient should be closely monitored and, when CKD is diagnosed based on IRIS guidelines, treatment recommendations should be provided based on IRIS staging.
• A negative result indicates the patient is not likely to have a diagnosis of CKD within the next 2 years; the patient should be re-evaluated at their next annual wellness examination, with no further action necessary until re-evaluation.
• Investigating for concurrent comorbidities that might predispose to, increase the risk for, or impact management of CKD should also be performed. This includes but is not limited to systemic hypertension, diabetes mellitus, hyperthyroidism, electrolyte abnormalities, and urolithiasis.
• If the result is inconclusive, it is recommended to re-evaluate and re-test the patient in 3 to 6 months.

Investigating for concurrent comorbidities that might predispose to, increase the risk for, or impact management of CKD should also be performed. This includes but is not limited to systemic hypertension, diabetes mellitus, hyperthyroidism, electrolyte abnormalities, and urolithiasis.

SDMA is a renal biomarker used to detect CKD earlier than can creatinine, when approximately only 40% of renal function has been lost.⁷ SDMA is used in the IRIS staging guidelines to help improve early diagnosis of CKD and individual patient management and recommendations. SDMA, which provides a snapshot of renal function at a single point in time, can be used alongside the RenalTech predictive algorithm to support an earlier CKD diagnosis and staging, as well as for monitoring of treatment and disease progression.

Mitzi returned to the clinic 3 weeks later for reassessment of her SDMA and creatinine levels. Although Mitzi’s creatinine was at the upper end of the normal laboratory reference range, she was diagnosed with IRIS stage 2 CKD based on interpretation of both her creatinine and SDMA levels. Studies have documented that, unlike serum creatinine levels which decline with muscle wasting, SDMA levels remain unaffected by this age-related change and are more highly correlated with glomerular filtration rate than serum creatinine.⁸

Mitzi’s isosthenuria, proteinuria, and hypertension were also supportive of kidney dysfunction and helped substage her CKD (ie, borderline proteinuric, hypertensive) and individualize her treatment plan moving forward. Before attributing her proteinuria and hypertension to kidney disease, it was crucial to rule out the presence of other comorbidities such as endocrine disease (eg, hyperthyroidism, diabetes mellitus) and lower urinary tract disease (eg, UTI, urolithiasis) that could also cause these abnormalities.

By utilizing both RenalTech and SDMA technologies, Mitzi was appropriately diagnosed with IRIS stage 2 CKD earlier than if her diagnosis had relied on creatinine alone. Mitzi was started on a renal therapeutic diet and an antihypertensive medication. It was recommended that Mitzi return in 2 weeks for repeat diagnostics to monitor her response to treatment and allow for additional medication adjustments.

Incorporating both RenalTech and SDMA technologies allows veterinarians to provide early care and recommendations for patients with CKD. RenalTech can help shape the approach to CKD in cats from a reactive perspective to a proactive one; by using and interpreting more than traditional serum BUN and creatinine levels, patients are able to be diagnosed with CKD sooner and receive individualized treatment plans that are tailored to their unique health status.² RenalTech can help improve owner confidence and compliance, ultimately leading to improved patient care and outcome. As early care strategies continue to emerge, the outlook for CKD continues to improve.

A 6-year-old, 55-lb (25-kg) spayed boxer was presented for a dental consultation regarding gingival masses (Figure 1) identified 2 months prior. Temperature, heart and respiratory rates, and the remainder of the physical examination were within normal limits. Clinical assessment and preanesthetic diagnostic investigation, including CBC and serum chemistry profile, were also within normal limits. During the examination of the patient’s head and oral cavity, a class III malocclusion was confirmed. Although this type of occlusion is typical for brachycephalic breeds, the maxillary incisors in this patient were causing trauma to the mandibular oral mucosa lingual to the mandibular incisors. The patient did not show signs of brachycephalic obstructive airway syndrome.

A thorough evaluation of the oral cavity (Figure 2) was performed with the patient under general anesthesia. Mandibular first premolars were not visible on clinical inspection. Mandibular mucosal trauma by the maxillary incisors and trauma to the left mandibular canine (304) tooth by the left second maxillary incisor (202) were observed. The patient also had oral masses present at the gingiva of the left rostral maxillary area covering the buccal surface of the premolar teeth (Figure 1).

Full-mouth radiographs were obtained, with particular attention on the clinically missing mandibular premolars and the areas affected by gingival masses. Radiographs revealed unerupted mandibular 1st premolars situated in apparent cystic lesions, expansion of which resulted in involvement of the mandibular canines and 2nd premolar teeth. The apical portion of the mesial root of the mandibular premolar (306) was partially resorbed. Maxillary premolars were rotated bilaterally, but there were no periodontal consequences. Incidental findings included a supernumerary maxillary left first premolar 1 (205) and fusion of the roots of the left and right mandibular premolar 2 teeth (306 and 406). Horizontal alveolar bone loss was present at the area of 206, with radiolucency of the furcation area of 206 (Figures 3-6); the buccal aspect of 206 was covered by the gingival mass. Probing of the furcation was possible only from the palatal side and did not reveal furcation involvement.

The following treatment plan was initiated based on clinical findings:

• Extraction of unerupted mandibular premolars, debridement of cysts, and submission of removed tissue for histopathologic evaluation. Due to lack of definitive histopathologic diagnosis and no mobility of 306 and 406, the pet owner declined extraction of these teeth until planned follow-up.
• Odontoplasty to reduce the crown height of the maxillary incisors to prevent trauma to the soft tissue and canine teeth. An alternative treatment option would include extraction of involved teeth. Radiographically, bone was present around the apices of 306 and 406; however, there was no indication to extract these teeth, as the cyst lining had been removed and thus new bone would fill the defect within a couple months.
• Excisional biopsy of gingival enlargement at the area of the left maxillary canine tooth and submission for histopathologic assessment, followed by gingivoplasty to correct the size and shape of the gingival tissue.

The procedures were routine and without complications. The bony void where the cystic lesion was removed was allowed to fill with blood prior to the site being sutured closed, as this promotes primary healing, which includes the formation of new bone. The patient’s size and limited extent of bone damage did not require use of grafting material to fill the empty space after cyst removal. A CO₂ laser was used to perform excisional biopsy of the gingival enlargement to decrease surgical time. After odontoplasty, there was no longer contact between the maxillary incisors and oral mucosa or the mandibular canine tooth. The maxillary incisor teeth that had undergone crown reduction were sealed with a dental varnish to protect the newly exposed dentin. An analgesic (ie, meloxicam [0.2 mg/kg IM, followed by daily oral doses of 0.1 mg/kg for 5 days]) was prescribed and application of an oral cleansing gel containing zinc ascorbate was advised for 14 days postoperatively.

Dentigerous cysts on the mandibular lesion and focal fibrous hyperplasia of the maxillary mass were confirmed via histopathology postoperation. At the 2-week postoperative recheck, the histopathology results were discussed with the owner and home care and further monitoring were established. Gingival enlargement may be plaque-associated or of a benign or malignant nature, and, because they are commonly found in boxer dogs, it is prudent for the owner to monitor the gingiva regularly. Plaque-associated gingival masses can be controlled with daily tooth brushing. Other benign or malignant lesions will commonly regrow following excision.

Brachycephalic breeds are predisposed to certain pathologies, including dental retention, dentigerous cysts, and neoplastic and benign gingival enlargement.^1-5 Anatomic features of brachycephalic breeds typically lead to painful traumatic malocclusion, which can only be confirmed via thorough oral examination. Because maxillary teeth crowding and gingival enlargement are strong causative factors for periodontal disease, this condition may develop sooner in brachycephalic breeds.

Systematic daily home care and regularly performed professional dental care can slow the return of gingival enlargement. It is essential to submit all excisions for histopathologic evaluation, as peripheral odontogentic fibroma, acanthomatous ameloblastoma, and gingival enlargement may have the same presentation.⁶

Approximately 30% of retained teeth result in odontogenic (ie, dentigerous) cysts, which destroy and weaken the bone, may cause pain, and can cause complications such as pathologic fractures or malignant transformation.^5-7 Clinically missing teeth require radiographic evaluation, and intervention, if needed, should be prompt.⁷

Many pathologic situations, such as the one described in this article, are typically ignored and/or underestimated by owners and primary care clinicians. Despite appearing painful and bothersome, these pathologies may not cause significant behavior changes. Thus, thorough oral examinations should be performed regularly in all brachycephalic patients to assist with early diagnosis and prevention of periodontal disease.

Systemic hypertension is commonly accompanied by secondary ocular changes (ie, feline hypertensive oculopathy), often leading to referral to a veterinary ophthalmologist for further management due to the risk for blindness in these patients. Ocular signs of systemic hypertension typically involve the posterior segment of the eye (eg, retinal detachment, retinal edema and hemorrhage, retinal degeneration); however, the anterior segment can also be involved. This primarily manifests as hyphema or changes in the iris vasculature.¹

In this retrospective study, medical records of 206 cats with documented hypertension (systolic blood pressure, >170 mm Hg), fundic changes typical of hypertension in at least one eye, and at least one follow-up visit with documented response to amlodipine were reviewed with the purpose of describing the prevalence and cause of iris aneurysm in cats with hypertensive oculopathy. Of the 206 cats, 14% had vascular changes of the iris that were consistent with iris aneurysm. Hyphema was present in 30% of all cats; of those with iris vasculature changes, 75% had hyphema. A strong correlation was found between iris aneurysm and hyphema, suggesting that leaky iridal vessels secondary to hypertension may be a common cause of hyphema in these patients. Previous studies have proposed hyphema in hypertensive cats to be caused by massive posterior segment hemorrhage migrating through the pupil.¹

Fundic changes and hyphema were negatively correlated in this study. Of the cats with grade I (ie, retinal folds) or grade II (ie, focal retinal edema/bullous elevation) fundic changes secondary to systemic hypertension, 57.1% and 59.4%, respectively, had hyphema. However, cats with grade III (ie, segmental retinal detachment/hemorrhage) and grade IV (ie, full retinal detachment/hemorrhage) fundic changes had a lower percentage of hyphema (23.9% and 18.8%, respectively). This indicates that hyphema in cats with systemic hypertension is more commonly seen when less severe, nonhemorrhagic fundic changes are present.

Histopathologic examination was performed on one eye in this study and confirmed the presence of iris aneurysm, which was noted to likely be the cause of hyphema for that patient, thus providing further evidence that hyphema secondary to systemic hypertension in cats may be associated with iris vasculature changes.

Key pearls to put into practice:

Early referral to a veterinary ophthalmologist for management of the ocular signs secondary to feline systemic hypertension is important for the success of these patients.

Blood pressure should be measured in all patients presented with hyphema.

This study’s findings cannot be generalized to canine patients; iridal vascular changes seen in cats with systemic hypertension may be secondary to species-specific characteristics of the iris vessels.

In this study, dogs between 8 and 12 weeks of age were examined to evaluate occlusion. Dogs were categorized as either individuals or members of a litter and further classified as purebred or crossbreed. Occlusions were evaluated by class and level of severity. Of the 297 dogs in the study population, 25.9% were identified as having malocclusion. Individual purebred dogs had a significantly higher percentage (33.8%) of malocclusion as compared with individual crossbreed dogs (20%). For dogs in litters, no purebred dogs were noted to have malocclusion, but 23.5% of crossbreed dogs in litters were presented with malocclusion. When all groups were combined, there was no significant difference in prevalence of malocclusion between crossbreed and purebred dogs. 

Malocclusions in dogs can vary in severity and are classified based on the relationship of the maxilla and mandible. Class I malocclusion indicates a normal jaw relationship, but individual teeth may be malpositioned. Class II malocclusion describes occlusion in which the mandible is distal in position to the maxilla (ie, mandibular distocclusion). Class III malocclusion describes occlusion in which the maxilla is distal in position to the mandible (ie, maxillary distocclusion)¹; this particular malocclusion may be considered normal in some American Kennel Club breeds (eg, brachycephalic dogs). Malocclusions in dogs are common and can develop into significant patient morbidity if left untreated. The length of the mandibular canines can be problematic in malocclusion, and oronasal communication can develop from chronic abnormal contact of the mandibular canines with the maxillary hard and soft tissue.

Key pearls to put into practice:

Recognition of malocclusion at an early age is important to develop proactive treatment plans to reduce future patient morbidity.

The age of this study population (ie, 8-12 weeks) represents an ideal time to evaluate for malocclusion. Pet owners may not be aware of the presence of dental abnormalities in newly adopted puppies and are unlikely to understand the significance of malocclusion on the comfort and overall health of their pet. Occlusal evaluation should be an integral part of the puppy examination and should continue to be performed as the patient matures.

Once malocclusion is identified, treatment options should be discussed with the owner or the patient should be referred for evaluation by a board-certified veterinary dentist. Initiating treatment in patients with deciduous teeth should be strongly considered based on the relationship between malocclusions of deciduous and permanent teeth.^2,3

Treatment of malocclusion can include selective extractions of teeth or crown height reduction to remove the traumatic contact between abnormally positioned teeth.^4,5

In humans, the risk for thromboembolism increases in hyperthyroid patients. Although it is known that cats with hyperthyroidism are prone to thromboembolism, the mechanism is unclear. This study compared platelet function in hyperthyroid cats with that in euthyroid age-matched cats. The study authors hypothesized that hyperthyroid cats would have platelet function abnormalities; however, this study did not find platelet function in these cats to be affected. In humans with hyperthyroidism, increases are seen in von Willebrand factor; this may be a source for further studies in feline patients.

As with all reflexes, there is a sensory and motor component to the cutaneous trunci reflex (CTR). The sensory input is via each segmental spinal nerve from T1 to L6, and the motor output is via the lateral thoracic nerve found between C8 and T1.¹ Sensory and motor innervation is bilateral; however, stimulation of one side can result in a contraction bilaterally. The CTR is used to reliably monitor neurologic progression in dogs with thoracolumbar spinal cord injury (eg, disk herniation, spinal fracture/subluxation, fibrocartilaginous embolism).² Evidence of ascending loss of CTR following thoracolumbar spinal cord injury could suggest a progression of myelomalacia and a worsening prognosis. Similarly, evidence of descending presence of the CTR could suggest improvement in spinal cord injury due to resolution of bruising, edema, and/or compression.

This study evaluated the CTR in 182 neurologically abnormal cats with neuroanatomic lesion localization anywhere in the central or peripheral nervous system; CTR was detectable in 64.8% of the cats. Statistical analysis did not identify an association between elicitation of the CTR and age, BCS, sex, breed, evidence of traumatic spinal cord injury, metabolic disease, level of mentation, or neuroanatomic lesion localization. Although evidence of spinal pain and CTR outcome was significantly associated, the authors were unable to illuminate the reason for this finding. 

This article supports the anecdotal clinical evidence that the CTR is unreliable in cats and should not be used to assess prognosis or determine the presence or absence of thoracolumbar spinal cord disease in cats. Furthermore, the authors suggest that evaluating the CTR may irritate the cat during the examination and make it less cooperative.

Key pearls to put into practice

Eliciting the CTR in cats is unreliable.

Evaluating the CTR in cats may aid neuroanatomic lesion localization if present but asymmetric; however, this may result in additional irritation to the patient and contribute to poor patient cooperation.

The absence of a CTR in cats has little to no significance and should be disregarded by the clinician when attempting to determine the neuroanatomic lesion localization.

This study evaluated 2 commercially available visual aid devices, one using echolocation and the other a physical barrier that incorporates tactile sensation, on the ability of 12 chronically blind dogs’ transit time and number of collisions in a maze. All dogs had fewer collisions with the physical barrier device as compared with baseline. Smaller dogs (≤26 lb [11.8 kg]) had fewer collisions with the physical barrier device as compared with baseline or when acclimatized to the echolocation device. Larger dogs (>26 lb [11.8 kg]) completed the maze faster when using the echolocation device as compared with no device or when acclimatized to the physical barrier device. Owners did not note any improvement in quality of life or home navigation on surveys.

Calcium oxalate urolithiasis continues to be a focus of preventive care research in veterinary urology. Monitoring for stone occurrence and recurrence can be achieved through radiography and ultrasonography, but resolution and operator/technology limitations may prevent efficient monitoring. Current prevention options rely on dietary modification, alteration of pH, and decreasing calcium availability in the urine. This study used the urine calcium:creatinine (UCa:Cr) ratio to determine whether increased postprandial calcium excretion is associated with stone formation in male miniature schnauzers.

Dogs enrolled in the study were split into groups consisting of affected or previously affected stone formers versus breed-matched controls. All dogs were fed the same diet; urine samples were collected before the dogs ate in the morning, then at 1, 2, 4, and 8 hours after eating. Nine affected dogs were included in the study, 5 of which had both nephroliths and uroliths. When all collection time points were evaluated, dogs with elevated urine calcium levels (UCa:Cr >0.05) were 13 times more likely to form stones. The calcium level of the urine in these dogs was likely to be higher at the 1- and 8-hour sample collection times; however, multiple dogs with uroliths had elevated calcium throughout the day. In addition, the authors found a potential link between dyslipidemia and stone formation that may parallel human stone etiopathogenesis.¹

At UCa:Cr ratio levels >0.06, there was good specificity (93%) but poor sensitivity (56%) for predicting calcium oxalate urolithiasis, with a modest positive predictive value of 83%. Despite multiple postprandial timepoints, the UCa:Cr ratio was unable to detect an increase in postprandial calciuresis, which may be due in part to experimental design.

The ability to detect increased calcium in the urine is promising if this can be connected to stone formation. Future studies may focus more on trending urine calcium levels and stone formation.

Key pearls to put into practice:

Owners of miniature schnauzers should be educated on the inherent risk for stone formation in their dog and how to identify urinary sand and grit prior to stone formation.

If stones are passed, voided, or removed, they should be submitted for stone analysis, and management options should be discussed with the owner when results are available.

Clinicians should stay apprised of the development of UCa:Cr ratio testing availability and consider this as a potential future tool for stone prevention.

The intestinal tract is a highly specialized organ responsible for nutrient digestion and absorption. In intestinal tissue, several cell types (ie, epithelial, mesenchymal, hematopoietic) contribute to preserving normal peristaltic functions and maintaining competent physical barriers to luminal microorganisms. Lymphocytes reside in the submucosal layer of the intestines and are normally involved in immune surveillance, providing a line of defense against luminal pathogens. However, this same population of lymphoid cells can give rise to diverse inflammatory or neoplastic pathologies.

In dogs, 2 notable intestinal diseases include T-cell–rich lymphoplasmacytic inflammatory bowel disease (IBD) and T-cell intestinal lymphoma (LSA).^1-3 Because both pathologies have a population of predominately CD3+ T lymphocytes, differentiating between these clinical entities can be difficult, and definitive diagnosis may require a panel of tests, including histology, immunohistochemistry, and molecular profiling through PCR for antigen-receptor rearrangements.⁴ Identifying complementary surrogate biomarkers, which are reliable and aid in distinguishing inflammatory from neoplastic lymphoid pathologies, could advance veterinary medicine.

MicroRNAs are noncoding RNA sequences found in the genome that regulate translation of proteins following gene transcription. Based on their mechanism of action, microRNAs can control cell population phenotypes by regulating the expression of different signaling pathways that influence biologic behaviors.⁵ Pathologies that may be phenotypically similar or overlapping (eg, lymphoplasmacytic IBD, intestinal T-cell LSA) could have differential microRNA expression patterns, allowing for these clinically similar diseases to be distinguished from one another based on their microRNA profile.

This study examined the microRNA expression patterns derived from full-thickness intestinal biopsies collected from normal dogs and from dogs that had a confirmed diagnosis of T-cell–rich lymphoplasmacytic IBD or T-cell LSA. Out of 183 mature microRNA candidates, 12 specific microRNAs were selected based on their robust and highly differential expressions across groups (normal, IBD, LSA), as well as on their predicted functional role in pathologic lymphoid biology.

When evaluated across 8 normal, 8 IBD, and 8 T-cell LSA intestinal samples, the 12 microRNA panels produced differential patterns that could differentiate most (7 out of 8) cases of intestinal T-cell LSA from either normal intestine or T-cell–rich lymphoplasmacytic IBD. In general, intestinal T-cell LSA-associated microRNAs included upregulation of oncogenic microRNAs and downregulation of tumor-suppressive microRNAs. These preliminary findings derived from a small number of intestinal samples suggest that microRNA expression patterns could serve as an adjuvant molecular test to aid in the discrimination of intestinal T-cell LSA from other nonneoplastic intestinal T-cell pathologies.

Key pearls to put into practice:

Intestinal pathologies involving T cells can be difficult to clinically and phenotypically distinguish from one another without more advanced molecular diagnostics.

MicroRNAs can regulate cell biologic behavior by altering the expressions of proteins involved in diverse signaling cascades (tumor suppressor and oncogenic pathways).

Select microRNA expression panels can be useful in distinguishing intestinal T-cell LSA from nonneoplastic pathologies such as IBD, and microRNA profiling could be considered a complementary diagnostic test.

Vitamin D is a fat-soluble vitamin. Severe vitamin D deficiency can cause rickets or osteomalacia, and even subclinical vitamin D deficiency can have detrimental effects.¹ In humans with cardiovascular disease, low vitamin D levels have been associated with progressive disease and poorer outcomes. Vitamin D levels in cats, particularly cats with cardiomyopathy, have not been well-studied.

The biologically active form of vitamin D is calcitriol (1, 25[OH]₂D₃). Dogs and cats must obtain precursors for vitamin D from their diet, as they cannot convert precursors in the skin to vitamin D with exposure to ultraviolet light.² Dietary precursors include cholecalciferol (25[OH]D₃; vitamin D₃) from animal food sources and ergocalciferol (25[OH]D₂; vitamin D₂) from plant-based sources. Cats also form a C3 epimer of vitamin D₃ (3-epi).³ This epimer has also been observed in humans, rats, and dogs but at very low levels.^2,4,5 Assessment of vitamin D status is generally based on serum levels of precursors, as calcitriol is less stable in circulation.

The primary goal of this cross-sectional observational study was to determine if vitamin D status is lower in cats with cardiomyopathy.

As a secondary goal, this study also evaluated whether vitamin D levels were associated with certain patient variables or severity of cardiomyopathy.

Clinical cases of cats with echocardiographic evidence of left atrial enlargement secondary to any type of cardiomyopathy (n = 44), including hypertrophic, restrictive, dilated, or unclassified/nonspecific, were recruited. A group of normal cats (n = 56) was also enrolled for comparison. All cats had to be primarily fed a commercial cat food, and a detailed dietary history was obtained for each cat. A venous blood sample was collected from each cat and submitted for measurement of 25(OH)D₂, 25(OH)D₃, and 3-epi. Only 25(OH)D₃ and 3-epi levels were included in the final analysis; 25(OH)D₂ was below detectable limits for both groups.

Increasing age was significantly associated with decreasing levels of both 25(OH)D₃ and summation vitamin D levels (ie, 25[OH]D₃ combined with 3-epi), whereas left ventricular fractional shortening and survival times were positively correlated with 25(OH)D₃ and summation vitamin D levels. Cats with cardiomyopathy had significantly lower summation vitamin D levels. The cardiomyopathy group had higher estimated levels of dietary vitamin D intake, but no correlation between intake and serum levels of 25(OH)D₃, 3-epi, or summation vitamin D levels was noted.

Overall, older cats had lower levels of vitamin D. In addition, summation vitamin D levels were lower in cats with cardiomyopathy as compared with normal cats. Both 25(OH)D₃ and summation vitamin D levels were positively associated with fractional shortening and survival time. Of note, there were substantial levels of the epi-3 metabolite detected in both groups of cats, suggesting this metabolite is important in this species, and summation vitamin D may be a potentially more useful clinical index for assessment of vitamin D status in cats as compared with 25(OH)D₃ alone.

Key pearls to put into practice:

Both vitamin D₃ and its C3 epimer (3-epi) can be measured in cats, and levels of 3-epi appear to be higher in cats as compared with humans and dogs.

Age appears to have a significant effect on vitamin D levels in cats, and lower levels may be noted in older cats, regardless of cardiomyopathy status.

Vitamin D₃ and the summation of vitamin D₃ and 3-epi appear to be positively correlated with survival; lower levels may be noted in cats with more advanced cardiomyopathy and congestive heart failure.

Most clinical information on pet rabbits focuses on dental disease and facial abscesses; information on oral neoplasia in the literature is limited for these animals. This study retrospectively reviewed records from a population of pet rabbits in Japan over a 10-year period.

Rabbits have special anatomic and physiologic characteristics in relation to their mouths. These include incisor and cheek teeth being elodont and hypsodont, with their teeth continuing to grow throughout the rabbit’s lifetime.^1,2 Rabbits also have characteristic morphology of the maxilla and mandible, which allows for only a very small and narrow opening of the mouth.^1-2 These anatomic considerations can affect the clinician’s ability to perform an oral examination, testing, and treatment in rabbits with oral disease. 

Clinical signs of oral neoplasia in rabbits may be similar or identical to those of dental disease. Common clinical signs include dysphagia, ptyalism, weight loss, anorexia, and oral hemorrhage.^1,3-5 Physical examination findings can include oral mass, malocclusion, ulceration, and abnormal odor and/or drainage.^1,3-5

A thorough oral examination with the patient under sedation or general anesthesia is one of the most important diagnostic evaluations. Visual examination of the mouth of an awake rabbit is inherently limited and will not allow a thorough evaluation of the oral cavity. Diagnostic imaging (eg, skull and thoracic radiography, CT) for evaluation of masses involving the mouth or head can be useful. 

Blood work changes in this study were determined to be nonspecific for oral neoplasia. Definitive diagnosis requires either a cytologic sample (eg, fine-needle aspirate), soft tissue biopsy, or surgical resection and histopathology. 

In this study, 13 different tumor types were diagnosed in 18 rabbits: squamous cell carcinoma (n = 3), ameloblastoma (n = 2), fibrosarcoma (n = 2), osteosarcoma (n = 2), cementoma (n = 1), complex odontoma (n = 1), giant cell epulis (n = 1), sarcoma (n = 1), chondrosarcoma (n = 1), trichoepithelioma (n = 1), papilloma (n = 1), malignant melanoma (n = 1), and basal cell carcinoma (n = 1).

Treatment of oral neoplasia in the rabbits in this study included surgical debulking of the mass or an attempt at surgical resection.^3-5 Often, it was not possible to obtain clean margins at the time of surgery due to the aforementioned anatomic considerations of this species. Radiation therapy was performed in several patients in this study with positive clinical results. Tumor type may help determine response to certain treatment modalities. Several patients experienced tumor recurrence. Many of the rabbits required regular dental care (eg, trimming or adjustment of the incisor or cheek teeth) to manage overgrowth or malocclusion.

Key pearls to put into practice:

Oral tumors are uncommon in rabbits as compared with some other small mammal species (eg, hedgehogs, ferrets); however, the rate of occurrence in rabbits may be similar to that of dogs.

Age and sex predisposition may exist in rabbits with oral neoplasia. Middle- to older-age male rabbits may have higher risk for oral neoplasia.

Clinical signs of oral neoplasia in rabbits are often similar to those of dental disease, which is a more common condition. Clinical signs include dysphagia, dropping of food from the mouth, anorexia, malocclusion, ptyalism, and oral hemorrhage. Diagnostics such as imaging, cytology, and/or histopathology are required for definitive diagnosis.

Demodex canis, the most common Demodex species leading to canine demodicosis, is a normal part of the skin microbiota but can proliferate secondary to immunocompromise.^1,2 Demodicosis is characterized by time of onset (juvenile vs adult) and areas affected (localized vs generalized). Localized demodicosis is generally self-limiting, whereas generalized demodicosis can be difficult to treat.

Topical amitraz, the only FDA-approved drug for the treatment of demodicosis in the United States, has been considered the standard for decades. Treatment requires intense topical therapy and carries risk for severe adverse effects. Topical moxidectin formulations are labeled for demodicosis treatment in other countries but not in the United States. Additional treatments include ivermectin, moxidectin, doramectin, lime sulfur, milbemycin oxime, and isoxazolines.^3-5 Many treatments have a high risk for adverse effects, and some can be cost-prohibitive.

This article reviewed the use of isoxazolines in the treatment of demodicosis in dogs and cats, as well as the safety of orally administered formulations of these drugs.

Isoxazolines are FDA-approved for use against fleas and ticks. Oral canine formulations include afoxolaner, sarolaner, fluralaner, and lotilaner.⁶ Topical fluralaner is available for use in dogs and cats.⁷ Field trials and reports have demonstrated successful treatment of generalized demodicosis using isoxazolines^8-14:

• Oral fluralaner has been shown to decrease the number of mites identified on scrapings by 100% at day 56.⁸ Topically administered fluralaner had similar efficacy.⁹ Another field study demonstrated parasitological cure in dogs with juvenile and generalized demodicosis within 2 to 4 months.¹⁰
• Both oral afoxolaner and lotilaner have been shown to reduce mite numbers by ≈99.9% on day 56 and 100% on day 84.^11,12 
• Sarolaner has been shown to reduce mite numbers by 99.8% within 29 days with no live mites detected thereafter; the control treatment had a lower efficacy with a longer duration of treatment.¹³ A multicenter study found mite counts decreased by 100% by day 150 following monthly administration of sarolaner as compared with the control that resulted in 82.2% reduction at 6 months.¹⁴

No large studies have been performed to investigate efficacy of isoxazoline treatment of feline demodicosis, although reports describe elimination of D gatoi and D cati after a single dose of oral fluralaner.^15,16

Oral fluralaner, afoxolaner, and sarolaner have all been assessed for safety in 8-week-old puppies receiving ≤5 times the maximum dose^17,18; no major adverse effects or impact on growth have been associated with treatment.^19,20 In one study, oral sarolaner at ≤5 times the maximum dose was administered to adult beagles, with no adverse effects noted.¹⁹ In another study, oral lotilaner was administered to 112 cats, with no adverse effects documented.²⁰ Oral fluralaner in breeding dogs has not been shown to have significant impact on reproductive performance or semen quality when administered at 3 times the maximum dose from breeding until weaning.⁷

Many historical treatments for demodicosis cannot be used in dogs with the multidrug sensitivity gene (MDR1 gene, also known as ABCB1 gene) mutation.²¹ Isoxazolines have the potential to cause neurologic excitation in vertebrates by blocking γ-aminobutyric acid-gated chloride channels. Fluralaner has been evaluated in dogs homozygous for the MDR1 mutation, and only minor clinical findings not associated with treatment have been observed.²² One report described neurologic signs observed in some dogs when given sarolaner doses higher than recommended.²³ One clinical report noted transient neurologic abnormalities in a young dog after administration of fluralaner at the recommended dose.²³ The FDA has reported adverse neurologic reactions across the isoxazoline class but has stated this class is effective and safe for most animals.²⁴

Key pearls to put into practice:

Isoxazolines are not currently labeled for the treatment of demodicosis in the United States, but studies and clinical reports support their clinical use.

Isoxazolines appear to be well-tolerated in most dogs, with minimal adverse effects; however, neurologic adverse effects have been reported.

Findings suggest that fluralaner is well-tolerated in dogs with the MDR1 mutation.

Lymphoma is a major nasal cancer in cats, comprising ≤65% of nasal cancer cases.^1-3 Cancer-specific treatment options include radiation (local treatment), chemotherapy (systemic treatment), or a combination of both.^4-6 It is unclear whether local, systemic, or combined treatment should be used as a first-line approach for localized lymphoma in cats or whether chemotherapy should be reserved for certain disease stages or recurrences.^4-6 Furthermore, the rate and location of tumor progression after treatment with radiation alone have not been well-defined.

This multi-institutional retrospective study evaluated cats with presumed localized sinonasal lymphoma treated with radiation alone using 1 of 3 protocols. The objective was to describe the failure pattern, time to progression, and overall survival rate and to identify prognostic factors that predict outcome.

Fifty-one cats were included in the study; the most common clinical signs were nasal discharge (74.5%) and stertor/stridor (70.6%). Fifty-one percent of cats had advanced tumors (clinical stage III; orbital, nasopharyngeal, subcutaneous, or submucosal involvement). Tumor grade was available in 42 cats; 40 (95.2%) had a high-grade tumor. These data collectively suggest that lymphoma is an aggressive cancer in cats.

Clinical response to treatment was subjectively assessed (ie, improvement in nasal signs) in 50 cats; responses were characterized as complete in 40 cats (80%), partial in 8 cats (16%), and stable in 2 cats (4%). Objective assessment of tumor response based on imaging was difficult to assess, as there were no standardized timepoints. In the 50 cats in which clinical response to treatment was assessed, disease progression occurred in 49% in the following pattern: 9.8% local progression (sinonasal, nasopharynx, or both), 3.9% locoregional (regional lymph node involvement only), 5.9% local and locoregional, 17.6% systemic (extending to distant organs), and 11.8% local and systemic. Despite the lengthy overall median time to progression (ie, 32.4 months), when systemic progression occurred, it developed early (ie, within 1.5-7 months after radiation) in all but 2 cats.

Radiation protocol and other factors evaluated, including glucocorticoid use and tumor factors (eg, size, grade, location, stage), were not predictive of overall time to progression or overall survival time.

This study demonstrates that radiation is an effective treatment for localized sinonasal lymphoma with a long time to progression; however, in 33% of the cats, systemic disease progression occurred soon after radiation.

Key pearls to put into practice:

Because the most common clinical signs in this study were nasal discharge and stertor/stridor, nasal lymphoma should be high on the differential list for cats presented with chronic and/or recurrent nasal signs.

Most cats were diagnosed with advanced-stage and high-grade phenotype; however, many experienced long-term benefits from radiation treatment.

One-third of cats experienced early systemic progression. Full staging was not required in this study; however, full staging is recommended for clinical cases so the best treatment protocol can be planned. If there is clear evidence of systemic disease, combination therapy (ie, radiation and chemotherapy) may be beneficial.

The ability to differentiate cardiac from noncardiac causes of respiratory distress is critical for enabling rapid initiation of appropriate treatment. FOCUS (focused cardiac ultrasound) is used in human medicine to help assess dyspneic patients in emergency situations. This study evaluated the use of FOCUS for differentiating cardiac from noncardiac causes of respiratory distress in veterinary patients. Emergency medicine and critical care clinicians categorized 38 dogs with respiratory distress as cardiac or noncardiac both before and after FOCUS. The accuracy of these diagnoses was calculated against a reference diagnosis, which was determined on the basis of consensus between a board-certified cardiologist and a board-certified emergency medicine and critical care specialist. Overall percent agreement between the emergency clinician and the reference diagnosis was 77.1% before FOCUS and 85.7% after FOCUS. Although FOCUS was helpful as compared with a physical examination and medical history alone, the difference was not statistically significant. In addition, a small percentage of dogs remained incorrectly diagnosed post-FOCUS. FOCUS also did not change the percent agreement between diagnoses made by faculty versus those made by residents.

Several breeds (eg, Jack Russell terriers, Akitas, pit bull terriers) have been shown to exhibit a higher incidence of aggression toward other dogs.^6,7 Conformation-bred English springer spaniels have been shown to be more aggressive toward other dogs as compared with field-bred springer spaniels.⁶ Other studies suggest that intact male dogs have a higher incidence of aggression as compared with neutered male dogs⁷ and female dogs have a higher incidence of aggression toward other dogs as compared with male dogs.⁸ Dogs not socialized during the socialization window (3-14 weeks of age) and those not living with other dogs are more likely to have increased aggression toward unfamiliar dogs.⁷ Territorial aggression and generalized anxiety are common comorbidities associated with interdog aggression.⁸

Because a genetic predisposition for behavior problems is possible, it is not recommended to breed dogs that demonstrate signs of aggressive behavior.

Spaying and neutering are unlikely to resolve aggression toward other dogs unless the aggression is between intact males and associated with competition for access to a female in estrus. Studies have shown that age at gonadectomy does not seem to affect incidence of aggression toward other dogs.⁹

In a comprehensive survey study of risk factors for human-directed aggression,¹⁰ spayed dogs were less likely to show aggression toward either familiar or unfamiliar humans. As the age of the dog increased, so did the incidence of aggression toward unfamiliar humans. Working dogs and hounds had higher risk for aggression toward familiar humans, and gun dogs (ie, bird dogs) had decreased risk for aggression toward unfamiliar humans. Dogs that attended a puppy training class had decreased risk for aggression toward unfamiliar humans. Punitive methods of training were shown to increase the possibility of aggression toward both unfamiliar and familiar humans. However, it is important to note there was only a small amount of variance between aggressive and nonaggressive dogs, meaning that although these general characteristics may be true at the population level, it is unlikely each dog’s ultimate risk can be determined based on characteristics such as breed. A dog’s history and experiences are likely to be more important.

As with canine-directed aggression, breeding is not recommended, and spaying or neutering after onset is unlikely to affect incidence.

The approach to diagnosis and treatment is similar for both human-directed and canine-directed aggression and should begin with taking a thorough behavior history; the SOCRATES Mnemonic for Pain Assessment was originally developed for assessing pain but can be modified to assess a history of aggression.¹¹

A primary clinical disorder that could contribute to or cause aggression should also be ruled out (see Aggression Caused by a Medical Condition), as increased patient irritability can lead to or increase the likelihood of behavior disorders, even when no clinical underpinning is evident.¹² A physical examination (including orthopedic and neurologic evaluation), CBC, serum chemistry profile, and urinalysis should be performed and followed by further testing (eg, imaging, endocrine testing) as indicated by initial diagnostics. After clinical disorders have been ruled out or appropriately treated, the behavior disorder can be addressed with a comprehensive treatment plan.

Aggression can be diagnosed based on the target and motivation of aggression. Targets are either familiar (eg, typically dogs or humans living in the same household, frequent household visitors) or unfamiliar. Humans considered familiar by the owner can still be considered unfamiliar by the dog. It is important to identify the target because management, behavior modification strategies, and prognosis differ based on the target.

Aggression may be based on the following:

• Fear (seen with offensive or defensive body posture in response to proximity with another dog)
• Resources (ie, conflict associated with resources [eg, food, toys, high-value bones, access to spaces, resting spots, human attention])
• Arousal (ie, a state of high-excitement [eg, when the doorbell rings] or overly exuberant play that switches to aggression toward another dog)
• Handling (eg, ear cleanings, paws being wiped, fur being brushed, nail trims, leash/collar/harness being clipped on)
• Redirection (ie, target of the aggression cannot be reached, so aggressive behavior is directed at an alternate target [eg, a dog being walked on leash with its housemate shows aggression toward an unfamiliar dog but attacks the housemate])
• Predation (ie, aggression directed toward smaller dogs that is often silent, with no warning except perhaps stalking and staring at the target)
• Social conflict between 2 dogs competing for social hierarchy

Management is the first step in a comprehensive treatment plan for aggression and begins with identification and avoidance of triggering situations. Owners should be able to recognize signs of fear, anxiety, stress, and nonverbal precursors of aggression in their pet to help predict and avoid aggressive episodes; these signs include defensive postures such as pinned-back ears, lip licking, panting, wrinkled brow, gaze aversion, rapid blinking, wrinkled nose, crouched body, and tucked tail. Offensive postures include a high-held tail, leaning forward, direct staring, erect ears, and a tall, stiff body position. Recognition of body language is especially important when complete separation or management is not feasible.

When the target is an unfamiliar dog, locations such as dog parks, doggy daycare, and clinic and groomer waiting rooms should be avoided. At the clinic, owners can stay in their vehicle with the dog until they can be taken straight to the examination room. Triggering situations (eg, leash walking during high-traffic times, leash walking in areas in which other dogs may be encountered, guests bringing a dog to the home) should also be avoided.

When the target is unfamiliar humans, avoidance can include not allowing visitors in the home unless the dog is confined in another room, taking the dog on a leashed walk during low-traffic times and in locations in which a minimal number of humans will be encountered, crossing the street when others are approaching, and never allowing unfamiliar humans to pet the dog.

When the aggression target is a familiar dog or human, complete avoidance can be difficult. Conflict over resources can be avoided by feeding the dogs in separate confined locations and providing high-value bones, chews, or toys only during separation or confinement. Management of all resources may be necessary in some cases, especially if the owner is unable to effectively monitor or identify body language indicators, but can increase stress and may not be possible in all cases. Arousal, redirected aggression, and predation can only be completely prevented by separate confinement of the dogs at all times, as the inciting triggers are often random and unpredictable and aggression can be triggered quickly with few warning signs.

Owners should be advised against attempting to take a stolen or given object (eg, chew bone) away from the dog. Aggression caused by fear, handling, redirection, or social conflict typically includes a behavior trigger (identified during the behavioral assessment); avoidance of the trigger is paramount and training is needed, including cue-response-reward–based training (eg, training the dog to stay off furniture), systematic desensitization, and/or counterconditioning to physical handling or use of a collar, leash, or harness.

Other management techniques include basket muzzle training (see Suggested Reading), using baby gates to confine the dog, or crate training. Muzzling does not prevent aggression but can prevent serious injuries when aggression is triggered. Muzzling a dog that remains in a provocative yet avoidable situation should be considered inhumane.

Behavior modification should follow management when treating aggression. General clinicians should emphasize the importance of behavior modification and refer owners to a board-certified trainer, behavior consultant, or veterinary behaviorist with appropriate credentials, educational background, and continuing education (see Suggested Reading). It is important to note that punishment tools (eg, shock collars [ie, stim collars, electronic collars], prong or pinch collars, choke collars, use of bags of chains or cans of pennies) and techniques (eg, leash popping, alpha rolls, other dominance-based methods) are not recommended. Many punishment-based trainers claim to treat aggression, but these techniques ultimately worsen the disorder and put the safety of the owner and others at risk.¹³

Medication therapy includes administration of products (eg, pheromones, nutraceuticals) and/or medication to decrease fear, anxiety, stress, and/or overall arousal. FDA-approved behavior medications are only approved for treatment of specific behaviors in dogs (eg, separation anxiety, noise aversion). These products and medications may caution against use for treatment of aggression due to possible bite disinhibition, in which anxiety preventing the dog from becoming more aggressive or using less inhibited forms of aggression is relieved. This potentially allows the dog to become more emboldened, more offensive, and less inhibited, thereby increasing the potential for aggression. This phenomenon is rare, but management strategies must be in place and owners warned of this potential before anxiolytic interventions are implemented.

There is anecdotal evidence that extra-label use of FDA-approved behavior medications for patients with aggression is common. Commonly used pharmacologic medications include selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline, paroxetine), tricyclic antidepressants (eg, clomipramine), α₂ agonists (eg, clonidine, dexmedetomidine), benzodiazepines (eg, alprazolam, diazepam, lorazepam, clorazepate), serotonin antagonist and reuptake inhibitors (eg, trazodone), and α₂δ ligands (eg, gabapentin). Commonly used supplements include pheromones (eg, dog- appeasing pheromone) and nutraceuticals (eg, L-theanine, α-casozepine).

Limited data are available on various medications and products. α-casozepine has been shown to be as effective as monoamine oxidase inhibitors (eg, selegiline) for treatment of anxiety-related disorders, although aggression was not specifically considered.¹⁴ Clonidine and fluoxetine in combination with clorazepate have been shown to help with aggression.^15,16 Trazodone has been shown to help dogs with anxiety-related disorders¹⁷ and thus could be useful in cases of aggression that are a result of fear or anxiety. In a small study comparing clomipramine with amitriptyline, clomipramine was shown to help with aggression and was as effective as amitriptyline in decreasing aggression.¹⁸

Patients should be individually evaluated to determine the best protocol to reduce daily and event-associated anxiety. Clinicians may need to consult with a board-certified veterinary behaviorist or a resident in clinical behavioral medicine to determine the best protocol.

Appropriate socialization in a safe, controlled environment when puppies are 3 to 14 weeks of age is critical to prevent aggression toward other dogs. Clinicians should not recommend avoiding other dogs until after the full round of vaccinations, as the risk for developing infectious diseases at puppy socialization classes has been shown to be negligible.¹⁹

Clinicians must inform owners of the prognosis and risk factors associated with dogs that are aggressive toward human members of the household, especially when euthanasia is a possibility. Risk factors that should be considered include²⁰:

• The family’s ability to manage the dog during treatment
• Severity of bites
• Number of bite incidents
• Members of the household (particularly those who are children, elderly, or cognitively impaired)
• Predictability of the aggression
• Size of the dog
• Context of the aggression
• Concurrent medical disease

Prognosis depends on the owner’s ability to identify the aggression triggers, manage and avoid those triggers, and recognize early warning signs of the aggression, as well as the size of the dogs involved, extent of any injuries that occurred previously, and the dog’s initial response to treatment. Setting realistic expectations is important so the owner can determine if they are capable of continuing treatment and assess the possibility of rehoming the dog. The clinician and owner can determine if humane euthanasia should be considered as an alternative option. If there are children or elderly people at risk, serious consideration should be made for rehoming or euthanasia.

Regular follow-up is essential to identify management and medication failures and to assess if the behavior modification program is progressing appropriately and whether adjustments should be made. Recheck evaluation should be performed at least every 4 weeks. Owners should meet with a veterinary behaviorist, trainer, or behavior consultant weekly or every other week. On recheck examination, improvement in intensity of the behavior, frequency of the behavior, and recovery period after being triggered should be assessed. Although a decrease should be seen in all of these areas after treatment, in severe cases, improvement may only be seen in intensity and recovery; frequency may only be decreased with strict management. Adjustments should be made if a 50% improvement is not seen at each recheck.

Canine aggression toward humans and other dogs is a common behavior complaint that can be treated with appropriate management strategies, anxiolytic products and medication, and behavior modification.

• Anemia of inflammatory/chronic disease
• Chronic renal disease
• Endocrine disease
  • Hyperestrogenism (eg, Sertoli cell tumor)
  • Hypoadrenocorticism
  • Hypothyroidism
• Hemophagocytic syndrome (secondary to histiocytic sarcoma, lymphoma, or other neoplastic, infectious, or immune-mediated disease)
• Hospital-acquired anemia (secondary to repeated blood sampling, surgery, inflammation, or hemodilution)
• Iron deficiency anemia; can be regenerative initially (eg, secondary to GI bleeding, ectoparasites [eg, fleas], or lead toxicity)
• Primary bone marrow disease (often with other concurrent cytopenias and/or dysplasia, except in cases of precursor-targeted immune-mediated anemia/pure red cell aplasia)
  • Congenital dyserythropoiesis
  • Drug-induced effect (often multifactorial [eg, estrogen, phenobarbital, sulfonamides])
  • Infectious disease (eg, FeLV/FIV, Ehrlichia spp, feline panleukopenia, canine parvovirus)
  • Myelodysplastic syndrome
  • Myelophthisis
    • Bone marrow necrosis/inflammation (eg, disseminated intravascular coagulation (DIC), sepsis, endotoxemia, drugs, toxins)
    • Myelofibrosis
    • Neoplasia (eg, lymphoma, leukemias, metastatic neoplasia)
  • Precursor-targeted immune-mediated anemia/pure red cell aplasia
• Sideroblastic anemia

• Hemolysis
  • Cold agglutinin disease 
  • Fragmentation anemia (eg, DIC, neoplasia [eg, hemangiosarcoma], liver disease, vasculitis, bacterial endocarditis, heartworm disease)
  • Hereditary cause
    • Feline congenital porphyria
    • Increased erythrocyte osmotic fragility (cats)
    • Phosphofructokinase deficiency (English springer spaniels, American cocker spaniels, whippets, Deutscher Wachtelhunds)
    • Pyruvate kinase deficiency (West Highland white terriers, Basenjis, beagles, cairn terriers, pugs, Labrador retrievers, domestic shorthair cats, Abyssinians, Somalis)
    • Spectrin deficiency (Dutch golden retrievers)
  • Hypophosphatemia (eg, treatment for diabetic ketoacidosis or refeeding syndrome)
  • Immune-mediated hemolytic anemia
    • Primary (idiopathic)
    • Secondary to underlying cause (eg, neoplasia, infection [eg, hemotropic Mycoplasma spp, Babesia spp], drugs, incompatible blood transfusion, envenomation)
  • Infectious cause (eg, hemotropic Mycoplasma spp, Babesia spp, Cytauxzoon felis, Leptospira spp)
  • Oxidant or Heinz body anemia (eg, secondary to onion or garlic ingestion, zinc toxicity [from pennies minted after 1982], copper toxicity [eg, copper hepatopathy], drugs [eg, acetaminophen, vitamin K], naphthalene, propylene glycol, benzocaine, skunk musk)
• Hemorrhage
  • GI ulceration (eg, secondary to NSAID administration, neoplasia, hypoadrenocorticism)
  • Hemostatic disorders
    • Coagulation disorder (eg, rodenticide toxicity [vitamin K antagonists], inherited coagulation deficiency [eg, hemophilia A])
    • DIC
    • Thrombocytopathy (eg, secondary reaction to monoclonal gammopathy, drugs [eg, aspirin])
    • Thrombocytopenia (eg, immune-mediated thrombocytopenia)
    • Von Willebrand disease
  • Neoplasia (eg, splenic hemangiosarcoma)
  • Parasitic disease (eg, fleas, hookworms)
  • Trauma (eg, vehicular, bite wound)
  • Vessel wall disorder (eg, vasculitis, colonic vascular ectasia)
• Normal puppies and kittens <8 weeks of age