1. Veterinary Specialists of South Florida Presents

2. Feline Idiopathic Cystitis
Kelly Alford, DVM

3. “Harley” 5 yo MN DSH PC: stranguria, pollakiuria, hematuria, periuria
No major medical history
48 hours in duration
Recently had an environmental change
Physical Examination
Unremarkable
Small urinary bladder that produced discomfort on palpation
Harley, a 5 yo MN DSH, presented for a 48 hour duration of stranguria, pollakiuria, hematuria and periuria. He had no major medical history and had recently had an environmental change. A hot water heater busted in the home, which resulted in flooding and multiple fans being used continuously. The owner stated that he had been hiding during the event and still wasn’t himself a week afterwards. On physical examination, Harley was found to be healthy. However, he did have a small urinary bladder that produced a reaction of discomfort on palpation.

4. “Harley” Urinalysis Other diagnostics declined USG = 1.046 Mild pyuria
Hematuria
Proteinuria
No bacteria seen
Other diagnostics declined
CBC, Chemistry
Radiographs
Urine culture

5. “Harley” Diagnosis Treatment
Tentative diagnosis of Feline Idiopathic Cystitis
Treatment
Buprenex
Phenoxybenzamine
Clavamox
Education
Environment
Water intake
Diet
Based on Harley’s age, history, clinical signs, and urinalysis results, he was tentatively diagnosed with feline idiopathic cystitis. He was sent home on buprenex, phenoxybenzamine and clavamox. The client was given information on the disease, environmental modifications, water intake and dietary recommendations that could help.

6. FLUTD Describes a condition of irritative voiding
Obstructive vs non-obstructive
Obstructive
Urethral plugs & idiopathic disease (90%)
Uroliths (10%)
Non-obstructive
Feline idiopathic cystitis (70%)
Urolithiasis (25%)
UTI
Feline lower urinary tract disease describes a condition of irritative voiding. It can be divided into obstructive vs non-obstructive disease. In obstructive disease the most common cause is urethral plugs and idiopathic disease, followed by uroliths. With non-obstructive disease the most common cause in younger cats are feline idiopathic cystitis followed by urolithiasis. In older cats it is urinary tract infections.

7. Feline Idiopathic Cystitis
Characterized by dysuria and hematuria
Male or female cats
Typically young adults (2-7yrs)
Routine aerobic cultures for bacteria usually negative
~ 1% of all cats in the US
High incidence of recurrence
35%
Feline Idiopathic Cystitis is an idiopathic syndrome of acute, self-limiting, irritative voiding that is often recurrent. You can see dysuria and hematuria in male and female cats, typically between the ages of 2-7 years. Of all cats of this age that present with hematuria and/or dysuria without obstruction, 2/3 are idiopathic and 1/3 have cystoliths. Routine aerobic cultures for bacteria are negative and this condition affects ~ 1% of all cats in the US population. LUTD accounts for 8-10% of cats presented to veterinary hospitals and >60% of these cases are idiopathic. There is a very high incidence of recurrence in the same cat (35%), esp if the 1st episode occurs when the cat is less than 4 yrs old (67%). Risk of recurrence diminishes with age.

8. Proposed Etiologies Viral
Herpes virus
Struvite Crystalluria (Ammonium Magnesium Phosphate)
Commonly noted in normal cats
No difference in struvite concentration in affected vs unaffected cats
In one study, 21 of 44 affected and clinical cats had no or few struvite crystals
Too little water intake?
Higher concentration, more concentrated urine in cats, less total water intake, dry food, recurrence
There are several proposed etiologies for this disease. In some experimental studies, a herpes virus was implicated, however experimental infection studies haven’t been repeatable. Struvite crystalluria is another proposed etiology, however this is commonly seen in normal cats. No difference in struvite concentration in urine was seen in affected vs unaffected cats. In one study, 21 of 44 affected and clinical cats had no or few struvite crystals. However, the theory is that if urine volume is low, struvite crystals will be concentrated. Cats have more concentrated urine than any other companion animal (mean of 100 = 1.057). Total water intake has been found to be less in cats on dry food. Cats with idiopathic cystitis tend to be fed more dry food than those cats without this problem. These cats have fewer recurrences when water intake is increased and urine concentration is less (dilution of struvite cyrstals or other factor).

9. Proposed Etiologies Stress/Environmental Spaying/Neutering? Obesity
Stress and environment also play a role, this disease seems to be more prevalent in colder weather (maybe they urinate less frequently whether or not forced indoors?) and when having recently moved (within 3 months). Cats are also found to be more likely to live in multicat households and have a conflict with a housemate cat. Early age spay or neuter (<14 wks), does not increase the risk for LUTD’s. Obesity may be a predisposing factor as affected cats tend to be overweight and have a decreased activity level.

10. Pathophysiology
Not completely understood but involves interactions between multiple body systems
Abnormalities in:
Bladder
< glycosaminoglycan's
Irritation of sensory neurons
Nervous system
Increased norepinephrine levels
Hypothalamic-pituitary-adrenal axis
The pathophysiology of FIC is not completely understood but involves interactions between the bladder, the nervous system and the hypothalamic-pituitary-adrenal axis. Cats with cystitis appear to excrete smaller than normal amounts of glycosaminoglycan's. This may permit irritation of the sensory neurons innervating the bladder by allowing particles to penetrate the urothelium. These neurons include unmyelinated nociceptive fibers (C fibers). Cats with FIC also have an increase in rate-limiting enzyme (tyrosine hydroxylase) in catecholamine synthesis in the locus coerulus (LC), which is the most important producer of norepinephrine in the feline CNS. Cats with FIC have increased plasma norepinephrine levels. Increased levels of norepi are thought to down-regulate alpha-2-adrenergic receptors, which play a role in regulating blood flow and urethral lubrication as well as an indirect role in bladder contractility. They also possess anti-nociceptive properties and may contribute to the cat’s perception of pelvic pain. Also, these cats that have an up-regulated sympathetic nervous system have decreased serum cortisol levels in response to ACTH. They also appear to have a less well-developed zona fasciculata and reticularis in their adrenal glands than healthy cats, which indicate a dissociation of the sympathetic nervous system from the hypothalamic-pituitary-axis.

11. FIC & IC FIC investigated as a model for IC in women
Histologic similarities
Glycosaminoglycan lining in bladder mucosa alterations
Differences between the two
Currently, FIC is being investigated as a model for interstitial cystitis in women, another idiopathic disease. There are some similarities in histologic findings as well as an alteration in the glycosaminoglycan lining of the bladder mucosa. Normal bladder urothelium is lined by GAG’s which inhibit bacterial adherence to the mucosa. They also protect the urothelium from noxious substances in the urine. FIC and IC excrete decreased amounts of GAG in the urine. If the GAG layer is compromised, irritative substances in urine may contact sensory nerves in the bladder endothelium, resulting in neurogenic bladder inflammation, which in turns releases inflammatory mediators for an inflammatory response. Some differences do exist, such as FIC occurs in males and female cats, while this affects only women. Also IC in women is a progressive disease, whereas FIC episode frequency and severity declines as the cat ages.

12. History Dysuria Hematuria Periuria
Urination in inappropriate places
Most common clinical sign
Differentiate from polyuria or urinary incontinence
Patients often have a history of dysuria with hematuria. The most common sign is periuria or urination in abnormal locations (sink, bathtub, etc.), which can be mistaken for a behavioral disorder. Approximately half of the cats that with inappropriate urination have been reported to have FIC. It is important to differentiate from clinical signs that can look similar to the owner, such as polyuria or urinary incontinence.

13. Physical Examination Usually unremarkable Small bladder Obese?
Firm and may spasm when palpated
Obese?
Evidence of perineal licking
Blood, crystals on perineal fur
The physical examination is usually largely unremarkable. However the bladder is small on palpation and may produce discomfort or spasms. Some of these cats are obese and you can see evidence of perineal licking or blood and crystals around the perineal region.

14. Diagnosis Idiopathic condition
Must rule out all other causes of the clinical findings
Diagnosis of exclusion
Diagnostics (UA, UCS, and imaging) don’t identify an etiology
The signalment can be helpful in identifying differential diagnosis. It is uncommon (<5%) for a cat older than 10 yrs to develop FIC and more than 50% of older cats have UTI’s. Likewise, it is unusual for a young cat to have a bacterial UTI. However, since this is an idiopathic condition, other causes of these clinical signs must be ruled out. Diagnostics don’t identify an etiology.

15. Clinicopathologic Findings
Laboratory work is often normal (except for the urinalysis)
Urinalysis
Hematuria
Proteinuria
Mild pyuria and struvite crystalluria
Bacterial culture – usually negative
pH – usually acidic
USG – usually concentrated
Basic bloodwork is often normal in these patients. The two most common abnormalities seen on urinalysis include hematuria and proteinuria and the severity can vary significantly over several days. The absence of hematuria doesn’t r/o FIC. Other findings include mild pyuria and struvite crystalluria (variable). Bacterial culture is often negative. The pH is usually acidic and the USG usually concentrated.

16. Imaging Studies Survey Radiographs Contrast radiology Ultrasound
r/o radiopaque stones
Contrast radiology
r/o radiolucent stones & urethral strictures
Ultrasound
Thickened bladder wall
Mucosal irregularities
Debris in lumen
Cystoscopy
Submucosal petechial hemorrhages
Survery radiographs are usually normal but help to r/o radiopaque stones that can be causing irritation to the bladder wall and LUT signs. Contrast radiology helps to rule out radiolucent uroliths and urethral strictures. A contrast urethrocystogram can show a thickened bladder wall. Results are normal in 85% of all FIC cats. On ultrasound the bladder wall is thickened, there is mucosal irregularities, and there may be small amounts of cellular or crystalline debris in the bladder lumen. Cystoscopy may reveal submucosal petechial hemorrhages. These are not seen in all cats with FIC and may be seen in some sensitive asymptomatic cats that have undergone recent stress. You can also see edema and increased vascularity. The severity of lesions doesn’t correlate with the severity of clinical signs.

17. When to pursue? First Tier Second Tier Urinalysis
Urine culture & sensitivity
+/- radiographs
Second Tier
Contrast radiology
Ultrasound
Cystoscopy
The first tier of diagnostics should include a UA, UCS +/- routine abdominal radiographs. Bloodwork should be pursued if concurrent diseases are suspected. If the episode is severe, persistent or the symptoms reoccur frequently, then the second tier of diagnostics may be indicated (contrast radiology, ultrasound, cystoscopy)

18. Treatment 70% of cats get better in 5 days Best treatment?
Regardless of therapy
40-50% relapse within 1 year
Best treatment?
Many treatments have no more effect than placebo
Studies show conflicting results about the benefits of specific therapies
Increase water consumption, pain management, environmental enrichment
FIC is a self-limiting disease and acute episodes typically resolve within 5 days with or without therapy, regardless of the type of therapy. Approximately 40-50% of those cats will relapse in 12 months. The current cause of this disorder is unknown, so treatment recommendations may be tentative. There is no “cure”, the aim of therapy is to decrease the severity of signs and to increase interepisode intervals, esp for severely affected cats. Many therapies show no more effect than a placebo. Studies have conflicting results regarding the benefits of specific types of therapies. The main focus’s are to increase water intake, pain management, and environmental enrichment.

19. Environmental Modifications
Reduce stress and decrease the severity and frequency of episodes
Litter boxes
N + 1 rule
Clean
Litter type and depth
Covered vs non-covered boxes
Location
Water and food dishes
Encourage activity
Climbing, scratching, hiding, and resting undisturbed
Environmental modifications are aimed at reducing stress and decreasing the severity and frequency of FIC episodes. The litter box should not be aversive to the cat. There should be 1 more litter box than the number of cats in the house hold. They should be clean, have appropriate litter and depth. Avoid strong smelling litter and cleaning products. Make sure they are in a private location, not where a lot of activity of draftiness is. The same N + 1 rule also applies to the food and water dishes, and they should also be kept clean. Also, encourage activity such as climbing, scratching, hiding and resting undisturbed. Stimulation is also important, such as plenty of toys or puzzle boxes.

20. Water Intake Increase water intake
Cats fed a canned diet had an 11% recurrence rate while cats fed dry diets had a 39% recurrence rate
Mechanism:
May decrease urine concentration (the concentration of noxious substances in the urine)
Methods to increase water intake
Keep fresh water available at all times
Pet water fountain
Canned food, may dilute with water
Put water in dry food
Subcutaneous fluids
USG < if effective
One study showed that cats fed a canned diet had an 11% recurrence rate over a year, vs a 39% recurrence rate in cats fed a dry diet. By increasing water intake, the urine concentration decreases, thus decreasing the concentration of noxious substances in the urine. There are several methods that can be employed to increase water intake. This includes keeping fresh water available at all times, keeping pet water fountain, feeding canned food, diluting wet or dry food with water, or administering SQ fluids. Ideally, the USG should be if effective.

21. Pheromonotherapy Feliway
Synthetic formulation of the feline facial pheromone
Decreases anxiety-related behavior
Feliway is a synthetic formulation of the feline facial pheromone that is used to decrease anxiety-related behavior in cats and is often used in conjunction with environmental enrichment.

22. Drug Therapy Analgesics Glucosamine Amitriptyline
Tricyclic antidepressant that may decrease sensory nerve fiber transmission in the bladder
Not effective in acute FIC episodes
May be effective in chronically relapsing cases
Non-steroidal anti-inflammatory’s
Carprofen, ketoprofen, meloxicam
Opioids
Buprenorphine, butorphanol, fentanyl
Glucosamine
Neutraceutical precursor for glycosaminoglycan's
Not effective in acute episodes but may be beneficial in chronically relapsing cases
Amitriptyline is a tricyclic antidepressant that may decrease sensory nerve fiber transmission in the bladder. It is not effective in acute episodes but may be beneficial in cats that have chronically relapsing episodes. In one study it was found that 9 of 15 cats had decreased clinical signs with severe recurrent FIC that failed to respond to other treatment. Consider pain relief for the “spastic bladder”. Pain relief can be used for cats with a current episode of FIC and can include NSAID’s, such as meloxicam, or opioids, such as buprenorphine and torb. Glucosamine is a neutraceutical precursor for glycosaminoglycan's. In one study there was no benefit observed when administered for 6 months to 20 cats with FIC, but there seems to be anecdotal success.

23. Other Treatments
There are other treatments that have been found to be no more effective than placebo
Antibiotics
SQ fluids
Smooth muscle relaxants
Anti-inflammatory dose of glucocorticoids
There are other treatments that are used, but show no benefit over placebos. Antibiotics, SQ fluids, smooth muscle relaxants and glucocorticoids at anti-inflammatory doses are a few of these.

24. Prognosis Self-limiting Recurrence is common
Overall it depends on the cat, client and environment
Cat
Duration of the problem
Frequency of occurrences
Client
Ability to ID modifiable causes
Willingness to pay for treatment
Amount of time to devote to solution
Willingness to accept and use medications
Environment
Number of cats in household
Number of affected cats
Ability to rearrange the environment
Most cases are self-limiting and resolve in a few days. However, recurrence can occur and the overall prognosis depends on the cat, client and environment. The duration of the problem and the frequency of occurrence with regards to each cat play a role. The client’s willingness and ability to modify the environment, pay for treatment and time to devote to the problem are extremely important. The environment itself, the number of cats and stressors, and the ability to adjust those factors also play a role.

25. We would like to thank you for your continued support and referrals.

26. References
Hostutler RA, Chew DJ, & DeBartola SP. Recent Concepts in Feline Lower Urinary Tract Disease. Vet Clin Small Anim. 35 (2005)
Ettinger SJ, Feldman EC: Textbook of Veterinary Internal Medicine. 6th ed. pp Copyright © Elsevier Inc.
Blackwell’s Five-minute Veterinary Consult: Canine & Feline, 4th edition. Tilley & Smith. Blackwell 2007,
Cote, E. Clinical Veterinary Advisor, Dogs and Cats. Elsevier, Inc., St. Louis, Missouri; 2007:
Goldstein, RE. Feline Lower Urinary Tract Disease. Cornell University, lecture notes