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Please be advised that this case report passed the ACVB Credentials Committee but we do NOT assert that every aspect of this case is perfect. It is provided as a general guideline.

Case Report #_ 123456

House-soiling in a 5yo MN Savannah .

Summary: A five year-old male castrated F4 “Bo” was evaluated for chronic urination outside of the litter box. Following a medical and behavioral assessment, the patient was diagnosed with urine marking based in territorial behavior. The patient was treated with environmental modification, changes to owner-cat interactions, and oral fluoxetine. Bo’s urine marking did not completely resolve, but the frequency was dramatically reduced to a level his owners could tolerate.

1 Signalment: Bo was a 5yo male castrated F4 savannah cat, weighing 4.7 kg.

Presenting Complaint: Bo was presented for chronic urination outside of the litter box.

History: Bo was acquired from a breeder at approximately 8 weeks of age. He lived in a detached house on a large rural property with his owners (a married couple) and a 7yo male castrated , Max. At about 2 years old, Bo began to urinate outside of his litter box. The owners first noticed urine on the carpet in the living room, near Bo’s favorite cat tree. Soon they discovered he was urinating in other locations, including the hallway to their bedroom, the kitchen garbage can, and on top of a hutch in the dining room.

Bo’s urine deposits outside of the box were relatively small, leaving puddles approximately 1-5 inches diameter on the ground. Urine was found mostly on horizontal surfaces, but were found occasionally on vertical surfaces (couch and garbage can). Bo did not vocalize or strain when he urinated, and was still using the litterbox normally for urination and defecation. He was not drinking or urinating excessively. The frequency of inappropriate urination changed over time, but for 3 months before consultation owners estimate 1-2 problem urination incidents/day. Bo’s owners noticed he urinated outside of the box more often in the Spring and Summer seasons.

Bo and Max were both strictly indoor . Owners reported the cat’s relationship as friendly and they were often found resting together and grooming each other. There were 3 large, uncovered litter boxes in the house, located in separate rooms, filled with unscented clay clumping litter and scooped several times weekly. Two cat trees were placed near large sunny windows in the living room. Both cats liked to climb on tall pieces of furniture such as bookcases. They also had access to and regularly used a 12’x12’ screened-in porch with vertical shelving. No scratching posts were available except for the cat trees, though Bo had shown a preference for carpet scratchers in the past. Two Feliway1 diffusers serviced the main living spaces.

2 The home was located in a rural area on a large property. Outdoor cats were often sighted, and

owners would leave kibble out for them. Several times per week, Bo was found growling and

hissing at outdoor cats through the windows in the living room, and on the screened-in porch.

Several spray bottles were kept throughout the house, and owners would use them multiple times

daily to discourage Bo’s urination outside of the box, jumping or scratching on furniture, and

vocalizing at outdoor cats. Owners felt this resulted in Bo urinating in their presence less often,

but the frequency of inappropriate urination was increasing over time.

When the owners first noticed Bo’s inappropriate urination, they had him evaluated by their

regular veterinarian. A urine sample collected from the carrier floor showed cocci bacteria but no

white blood cells on sediment evaluation (Appendix 1). The veterinarian recommended a 14-day course of amoxicillin with clavulanic acid. The owners felt that that the antibiotics made no difference in the frequency of Bo’s inappropriate urination, but he was very difficult to pill and they were not certain that he swallowed every dose. No follow-up lab work was performed.

When Bo was 4 years old, his owners had him evaluated by another veterinarian. No diagnostics were performed at this visit. The veterinarian suspected urine marking and recommended

Feliway1 diffusers, environmental enrichment, increasing the number of litter boxes (from 1 to

3). Oral fluoxetine was prescribed at 5mg once daily, but Bo quickly became resistant to restraint

and started to bite and scratch his owners when they tried to pill him. The referring veterinarian

then prescribed a compounded transdermal Lipoderm gel preparation of fluoxetine, at 25mg on

alternating ears once daily. Bo tolerated this medication, but 3 months later no improvement in

the problem urination was apparent. Bo’s veterinarian recommended referral at this point.

Observations, Physical Exam Findings, and Laboratory Results: Physical and orthopedic

examinations of Bo did not reveal any abnormal findings. His bladder was small, soft, and

3 comfortable on palpation. Bladder ultrasound revealed normal bladder wall thickness, and no

mineralized material or sludge in the urine. A cystocentesis urine sample was obtained for urinalysis, urine sediment microscopy, culture, and sensitivity testing. Blood tests (complete blood count, biochemistry panel, and T4) were also performed. Lab results levels were normal

(Appendix 1), and urine culture showed no bacterial growth.

Bo was up to date on , feline herpervirus 1, calicivirus, and panleukopenia vaccines.

Diagnosis: Medical differentials for Bo’s problem urination included lower urinary tract diseases such as a urinary tract infection (UTI), crystaluria, urolithiasis, or feline idiopathic cystitis

(FIC).[1, 2, 3] Urinalysis, negative urine culture, and ultrasound results ruled out UTI, crystaluria, and urolithiasis. Due to the lack of white blood cells on the first veterinarian’s urinalysis, the cocci bacteria found may have been environmental contamination and UTI could not be diagnosed without further testing.[3] FIC was considered unlikely due to a lack of historical hematuria, dysuria, or stranguria, and normal bladder wall thickness on ultrasound.[4,

5] Additionally, non-obstructive untreated FIC episodes have been shown to resolve in 92% of cases within 5-7 days[5], and Bo’s problem was more chronic. Cystoscopy or bladder wall biopsy could have been employed to rule-out FIC, neoplasia, or congenital defects.

Diseases which cause polyuria and/or polydipsia such as chronic kidney disease, diabetes mellitus, and hyperthyroidism were considered, but ruled out from normal glucose, urea, creatinine, urine specific gravity, and thyroid hormone levels.[7] Some disease processes may make it difficult for cats to locate the litter box (sensory deficits, neurologic conditions) or comfortably enter the litter box (arthritis, ataxia)[7], but Bo’s normal physical exam, orthopedic exam, and history of voluntarily jumping to high surfaces make these differentials unlikely.[8]

Behavioral differentials for Bo’s problem urination included urine marking, litter box aversion,

4 substrate aversion, or location aversion.[6, 7, 9] As Bo’s litter box use had not changed, aversions to the box, substrate, or locations was unlikely. The small volumes of urine, high frequency of urination, lack of substrate preference, and ongoing use of litter boxes all fit with a diagnosis of urine marking, however horizontal urination is less common with marking.[7,10,11]

Urine marking is most often performed against vertical surfaces, but some cats do mark on horizontal surfaces.[10,] Cats who urine mark on horizontal surfaces usually also mark on vertical surfaces.[12] Although urine marking is more common in sexually intact cats, 10-12% of neutered males also display the behavior.[13-15] Urine marking does not seem to correlate with urinary disease in cats.[16] Pre-disposing factors for urine marking include male sex, living in multi-cat households[17], and male cats living with a female cat.[15]

Urine marking is considered to be a communication tool rather than primarily an elimination behavior.[18] Although marking behavior has been described with both feces (middening) and urine, urine marking is more common in domestic cats.[19] Motivations for urine marking behavior include hormonal causes, overt or covert conflict with other household cats, territorial disputes, changes to environment or routine, and/or anxiety.[9,10] Bo was neutered by the referring veterinarian at 6 months of age, so hormonal causes could be ruled out.

Tension between household cats is a common underlying cause of urine marking behavior.[6,

7,17] Signs of inter-cat tension are often subtle, but as Bo and Max often engaged in affiliative behaviors (allogrooming and resting in close proximity[20-22]), this cause was considered less likely. Per owners, no significant changes had been made to Bo’s environment or schedule around the time of onset of the inappropriate urination.

The presence of unfamiliar cats on the property, Bo’s exposure to them through frequent use of the screened-in porch, and his aggressive behavior towards them (growling and hissing)[20-22]

5 indicated territorial behavior as the most likely motivation for Bo’s urine marking. Additionally,

Bo’s marking was more frequent in the Spring and Summer, which is when outdoor toms are likely to show increased roaming and marking behaviors.[19,23]

Fluoxetine has been shown to be over 90% effective in reducing urine marking behavior in cats when given orally at 1-1.5mg/kg once daily.[24] The PLO transdermal form of fluoxetine has been found to reduce the bioavailability of the medication by 90% compared to oral administration.[25] Lipoderm transdermal gel fluoxetine was also found to have significantly lower bioavailability compared to oral dosing.[26] Thus, a diagnosis of urine marking based in territorial behavior was made, despite lack of response to transdermal fluoxetine.

Treatment: Environmental modifications were recommended to decrease Bo’s exposure to the outdoor cats, and encourage natural, enriching behavior indoors. Owners were asked to stop feeding outdoor cats, remove bird feeders that might be attracting prey for outdoor cats, and block Bo’s access to the screened-in porch.[6,10] The two cat trees in the living room were moved to other areas of the room to remove window access, but retain access to vertical space.

Providing access to elevated spaces on top of furniture using shelving or cat trees[27], and discontinuing spray bottle punishment were also recommended.[10, 27] Otherwise, resources including food, water, resting areas, and litter boxed were already distributed well in this home.

Owners were instructed to clean litter boxes daily, wash boxes and freshen litter weekly, and clean up urine marks immediately with an enzymatic cleaner.[17] Feliway1 is a synthetic analogue of the feline facial pheromone (F3). Owners were advised to continue refilling Feliway1 diffusers, and begin applying Feliway1 spray on to previously marked areas to encourage facial pheromone marking.[28-31] Adding vertical and horizontal carpeted scratching posts to previously marked areas was recommended. Owners were asked to reward Bo for bunting (facial

6 marking) or scratching with attention or treats to encourage this form of marking behavior.[10]

Due to lack of clinical effect, transdermal fluoxetine gel was discontinued after 1 week at 50% of the dose. Owners were instructed to begin feeding Bo at least 3 Pill Pocket2 treats in a row with small pieces of kibble inside once daily before breakfast in a consistent location as training for voluntary consumption of oral medication.[32-33]

Follow-Up: Four weeks later, Bo’s owners reported his urine marking had reduced about 25% in frequency. Outdoor cat sightings were less frequent, but Bo had been found sitting on a window ledge growling at an outdoor cat 2 days previously. Owners were asked to close blinds or install opaque window film on any window through which Bo could view outdoor cats.[10]

Medication with oral fluoxetine at 5mg once daily (0.94mg/kg) was recommended due to strong clinical evidence of efficacy in controlling urine marking behavior.[24, 31, 34] The fluoxetine tablet was enclosed in the 2nd (middle) Pill Pocket2 of the routine described above. Fluoxetine is a selective serotonin re-uptake inhibitor which increases serotonergic neurotransmission by blocking the pre-synaptic re-uptake of serotonin, and long-term down-regulates post-synaptic serotonin receptors.[35, 36] Owners were informed of extra-label use for urine marking in cats, and potential side effects including hyporexia, vomiting, and lethargy.[24, 34]

Four weeks later Bo’s owners reported no side effects, and a reduction in urine marking of 75%.

Environmental management was going well and Bo did not seem to notice outdoor cats anymore.

The fluoxetine dose was increased to 7.5mg (1.6 mg/kg). Six months later, Bo was still voluntarily consuming the fluoxetine without side effects. The frequency of his marking behavior had decreased to approximately 2 episodes/month, which the owners could tolerate.

Weaning off fluoxetine was discussed but owners declined out of concern for recurrence of the marking behavior. Yearly blood work was recommended to monitor organ function.

7 Appendix 1: Lab data

URINALYSIS (from referring vet, 3 years prior to presentation)

Collection Method: Off carrier floor

Parameter Result Normal Range Units

Color Yellow N/A

Clarity Hazy N/A

Specific Gravity 1.047 N/A N/A

Glucose Negative Negative N/A

Bilirubin Negative Negative N/A

Ketones Negative Negative N/A

Blood Negative Negative N/A

pH 7.0 N/A N/A

Protein Negative Negative-trace N/A

WBC None seen 0-5 Per HPF

RBC None seen 0-5 Per HPF

Bacteria 2+ cocci N/A

Epi Cell None seen Per HPF

Casts None seen Per HPF

Crystals None seen Per HPF

Other Amorphous debris, lipid droplets N/A

8 COMPLETE BLOOD COUNT – performed at first consultation

Parameter Result Normal Range Units

Rbc 9.02 7.0-10.5 M/ul

Hemoglobin 12.8 10-16 g/dl

Hematocrit 42.4 30-50 %

MCV 43 42-53 fl

MCH 14.9 13-17 pgm

MCHC 31.3 30-33.5 gm/dl

RDW 15 14-18 %

Reticulocyte Count 8,040 7,000-60,000 /ul

RBC Morphology

Anisocytosis slight None-slight

Echinocytes none None-few

Leukocyte Parameters

WBC 12,211 4,500-14,000 /ul

Neutrophils 7,832 2,000-9,000 /ul

Lymphocytes 4,202 1,000-7,000 /ul

Monocytes 392 50-600 /ul

Eosinophils 1,128 150-1,100 /ul

Basophils 3 0-200 /ul

Other Parameters

Platelets 257 180-500 K/ul

9 T4 – performed at first consultation

Result Normal Range Units

T4 Total 1.8 1.1-3.3 Ug/dL

SERUM BIOCHEMISTRY – performed at first consultation

Parameter Result Normal Range Units

Anion Gap 20 13-27 mmol/L

Sodium 153 151-158 mmol/L

Potassium 4.2 3.6-4.9 mmol/L

Chloride 117 117-126 mmol/L

Bicarbonate 15 15-21 mmol/L

Phosphorus 5.1 3.2-6.3 mg/dL

Calcium 9.9 9.0-10.9 mg/dL

BUN 21 18-33 mg/dL

Creatinine 1.1 0.5-1.2 mg/dL

Glucose 111 63-118 mg/dL

Total Protein 7.4 6.6-8.4 g/dL

Albumin 3.2 2.2-4.6 g/dL

Globulin 3.7 2.8-5.4 g/dL

ALT 81 27-101 IU/L

AST 41 17-58 IU/L

Creatine Kinase 258 73-260 IU/L

10 Alkaline Phosphatase 18 14-71 IU/L

GGT 1 0-4 IU/L

Cholesterol 177 89-258 mg/dL

Bilirubin, Total 0.1 0.0-0.2 mg/dL

Magnesium 1.9 1.5-2.5 Mg/dl

Hemolysis Index 14 0-14

Icteric Index 0 0-4

Lipemic Index 0 <1

URINALYSIS – performed at first consultation

Parameter Result Normal Range Units

Color Yellow N/A

Clarity Clear N/A

Specific Gravity 1.042 N/A N/A

Glucose Negative Negative N/A

Bilirubin Negative Negative N/A

Ketones Negative Negative N/A

Blood Negative Negative N/A

pH 7.1 N/A N/A

Protein Negative Negative-trace N/A

WBC None seen 0-5 Per HPF

RBC None seen 0-5 Per HPF

Bacteria None seen N/A

Epi Cell None seen Per HPF

11 Casts None seen Per HPF

Crystals None seen Per HPF

URINE CLUTURE – performed at first consultation

No growth.

Footnotes

1Feliway, Ceva Health LLC., Lenexa, KS

2Pill Pockets, Mars Inc., McLean, VI

12 References

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16 Dr. ______:

The credentials committee is pleased to inform you that case report ______, “House-soiling in a 5yo MN Savannah cat”, has passed review. Congratulations.

Each reviewer’s comments are listed below:

Reviewer A: • Treatment: Were any other medications considered to gain higher degree of control? Either as supplement to fluoxetine or instead of fluoxetine? • Treatment: I do not see mention of any enrichment activities (such as foraging, clicker training, cognitive tasks, etc). Author may want to consider these options in the future. • Medical therapy alternatives: Was dietary intervention considered (such as Royal Canin Calm or SD Multicare Stress)? There is also no mention of other neutraceuticals that could be considered. • Grammar/Tone: The reference to "regular veterinarian" on page 3 is not professional. Consider options such as family veterinarian, general practitioner, etc. • Overall summary and impressions: I think the case was evaluated well medically and discussion of the potential differentials was excellent. It may have been a space constraint that limited discussion of other options for therapy to further decrease the occurrence of marking behaviors.

Reviewer B: • Overall summary and impressions: This was an unusual form of marking, because it was mostly horizontal and discovering the cause, the outdoor cats, was admirable. • Diagnosis: Should have mentioned the cat's was only 4 generations removed from the wild cat. • Treatment: I was impressed with treatment to encourage pill consumption. • Grammar: Several instances when number and verb did not agree. 1) Urine was found mostly on horizontal surfaces, but were found. Should be was found 2) 3 months before the consultation owners estimate. Should be estimated

Reviewer C: • Diagnosis: hormonal or social tension motivations not well described • Treatment: There was no mention of the potential for problems produced by a treatment. • Treatment: There was no mention of the potential for significant medical side effects associated with medication.

5003 SW 41st Blvd., Gainesville, FL 32608 [email protected] Ÿ www.dacvb.org Reviewer D: • Case selection: case required and included a good medical work up. • Case complexity: Case was actually complex with the territorial aggression and aversion to oral medication - should have been included into the summary • Differential supported by history and observations: lack of description of posture during elimination. • Complete working diagnosis: posture is important and missing. also did not rule out if the second cat is involved in the process • Treatment: could have considered additional medications or supplements • Overall summary and impressions: The case was actually good but missed some aspects that were highlighted such as multiple cat household, who is the culprit, territorial aggression and aversion of oral medication with difficulties to treat. Case could have had higher scores if that was addressed – points were lost due the descriptor of body posture during elimination.

We thank you for your submission and hope these comments are helpful to you as you prepare additional case reports and in future writing endeavors.

5003 SW 41st Blvd., Gainesville, FL 32608 [email protected] Ÿ www.dacvb.org