Idiopathic cystitis (Proceedings)

The most common cause of feline lower urinary tract disease is idiopathic cystitis. Feline idiopathic cystitis, formerly called idiopathic feline lower urinary tract disease, is defined as a disease of undetermined etiology characterized by hematuria, dysuria, pollakiuria and possible urethral plug formation. This condition overlaps with 2 clinical syndromes of dysuria/pollakiuria syndrome and urinary obstruction. The syndrome of dysuria/pollakiuria in cats is often associated with hematuria and was initially referred to as the "feline urologic syndrome" or "FUS". Idiopathic cystitis is one of several differential diagnoses for dysuria/pollakiuria in cats. Unfortunately many veterinarians assume all cats with dysuria/pollakiuria or urinary obstruction should all receive the same stereotyped treatment without first obtaining a diagnosis. This leads to frustration when cases don't resolve with treatment.

Diagnosis

Differential diagnoses for lower urinary tract diseases in young adult cats from most common to least common include idiopathic cystitis (with or without urethral plug formation), urolithiasis, iatrogenic disorders (urethral tears, urethral stricture), bacterial UTI, neoplasia (lymphoma, transitional cell carcinoma), fungal UTI, prostate disease, and idiopathic detrusor instability. The role of urachal diverticula in lower urinary tract disease in cats is controversial. While cats with diverticula may have persistent clinical signs that have been suggested to be caused by the diverticula, diverticula may spontaneously regress with resolution of lower urinary tract disease suggesting the diverticula are a result of the disease rather than a cause of the disease.6 The causes of lower urinary tract disease in geriatric cats are different than young adult cats. In one study of geriatric cats, the causes from most common to least common were UTI (46%), urolithiasis with UTI (17%), urolithiasis without UTI (10%), urethral plugs (7%), traumatic injury (7%), idiopathic cystitis (5%), and neoplasia (3%). The higher incidence of UTI in geriatric cats versus only 1-2% incidence of UTI in young adult cats with lower urinary tract disease is due to underlying diseases that predispose geriatric cats to UTI such as chronic kidney disease, diabetes mellitus, and hyperthyroidism.

Diagnosis of idiopathic cystitis is based on ruling out other known causes of lower urinary tract disease; it is an exclusion diagnosis. The minimum work-up should consist of a urinalysis, urine culture, and abdominal radiographs, although these do not rule-out all possible causes of lower urinary tract disease. Cases that persist beyond 5 to 7 days may require additional work-up, such as ultrasound or contrast radiographs to rule out radiolucent uroliths and neoplasia, and urine cultures for unusual organisms (mycoplasma and ureaplasma). Cystoscopy may be used to confirm the diagnosis of idiopathic cystitis.

Idiopathic cystitis

There are two clinical forms of idiopathic cystitis: nonobstructive and obstructive. In the nonobstructive form, male or female cats present with a history of hematuria, dysuria, and pollakiuria. There tend to be episodic clinical signs with acute onset. Understanding the natural course of the disease is critical to accurately interpret any proposed treatment effects. Idiopathic cystitis usually resolves spontaneously within 5 to 7 days regardless of treatment, thus any therapy may appear effective. Recurrence is common but unpredictable; cats can be normal for days to years between episodes. The obstructive form occurs in male cats due to occlusion of the urethra by urethral "plugs". Urethral plugs are not uroliths, rather uroliths are a differential diagnosis for cause of urethral obstruction. Urethral plugs differ from uroliths in that they lack organized internal structure. They are semi-solid plugs composed of matrix and crystals (usually struvite) and often have the consistency of thick toothpaste. The matrix consists of varying quantities of proteins and cellular debris (RBC, WBC, epithelial cells). If obstruction is due to true uroliths, the cause is urolithiasis, not idiopathic cystitis. Massive crystalluria can lead to the formation of multiple small uroliths, which are like "sand" and can cause obstruction. This illustrates a continuum between urethral plugs and urolithiasis. Urethral obstruction may occur abruptly without prior clinical signs or may be preceded by dysuria/pollakiuria. Urethral matrix plugs may begin to form in female cats and non-obstructed male cats, but they pass out the urethra without becoming lodged. Increased crystalline component of urethral plugs may solidify the plug causing obstruction. Urethral obstruction is life-threatening. Urethral obstruction tends to recur with subsequent episodes of idiopathic cystitis.

The etiology of idiopathic cystitis is unknown, but there are three main hypotheses on its origin. Viral infection of the lower urinary tract has been hypothesized to cause idiopathic cystitis. Experimental studies have suggested that infection of the feline lower urinary tract with a cell-associated herpesvirus (CAHV) may induce hematuria in young SPF cats. CAHV can persist in lower urinary tract tissues for prolonged periods of time; however, CAHV does not reliably produce the typical clinical disease. It does, however, resemble herpesvirus infections in other species (genital herpes infections in man) and represents an attractive hypothesis for pathogenesis. Viral particles have been identified in many spontaneous urethral plugs but they may represent causative agents or they may simply reflect urinary excretion from viremia.

Excess dietary intake of minerals (magnesium) resulting in struvite crystalluria has been hypothesized to cause idiopathic cystitis. The crystals hypothetically irritate the bladder mucosa resulting in inflammation. Support for this theory is even weaker than the viral hypothesis. Data supporting this hypothesis is based primarily on experimental models of feline struvite urolithiasis and does not support crystalluria as a cause of idiopathic cystitis. Crystalluria probably does play a role in the genesis of urethral obstruction due to urethral plugs. The crystals act to solidify the plug resulting in obstruction. While most urethral plugs contain struvite crystals entrapped within the matrix plug; some urethral plugs may contain calcium oxalate or urate crystals or and some plugs lack any crystalline component. Indirect evidence suggests that dietary therapy designed to prevent struvite crystalluria reduces the incidence of recurrent urinary obstruction.

Drs. Buffington, Chew and Westropp have suggested that idiopathic cystitis is feline interstitial cystitis, similar to human interstitial cystitis which occurs mainly in women. The etiology of human interstitial cystitis is also unknown. Cats with idiopathic cystitis have decreased size and function of their adrenal glands. The specific cause and effect link between the adrenal abnormalities and FIC in these cats is not known, but this may provide insight into the pathogenesis of this disorder. This also correlates to observations that cats with idiopathic cystitis tend the have recurrences during periods of environmental "stress". Cats with idiopathic cystitis have increased catecholamine levels and increased bladder permeability during periods of stress.

Treatment of Idiopathic Cystitis

There is no proven effective therapy for treatment of idiopathic cystitis. The disease usually resolves spontaneously within 5-7 days in non-obstructed cats. Antibiotics are only indicated for documented UTI or prophylaxis following indwelling urethral catheterization. Management of urinary obstruction is similar to urinary obstruction of other causes. Although several treatments have been suggested for idiopathic cystitis, none have been proven more effective than placebo. Antibiotics are not effective in treatment of idiopathic cystitis. Methylene blue (a urinary antiseptic) and phenazopyridine (a urinary analgesic) are contraindicated in cats because they cause Heinz body hemolytic anemia and methemoglobinemia. Corticosteroids have been suggested to reduce inflammation in idiopathic cystitis, but a double-blind clinical trial showed no improvement with steroids compared to placebo. Prednisone also did not reduce inflammation in an experimental model of idiopathic cystitis and predisposed the cats to UTI and pyelonephritis. Steroids increase catabolism, which can worsen postrenal uremia from obstruction. Intravesical DMSO also was not beneficial, and it may predispose the cat to UTI and pyelonephritis. Intravesical PGE1 was also not effective in an experimental model of interstitial cystitis. Propantheline is an antispasmodic that may reduce the severity and frequency of "urge" incontinence in cats with non-obstructed idiopathic cystitis. However, this is symptomatic only and does not affect the rate of recovery. Although there is no research data to support narcotics, some clinicians recommend narcotic analgesia to reduce clinical signs during acute episodes of idiopathic cystitis. Oral butorphanol (0.5-1 mg/kg PO q6-8h) or sublingual (buccal) buprenorphine (0.01-0.03 mg/kg q 6-8 h) may be used to alleviate pain.

Prevention of Idiopathic Cystitis

There is also no proven preventative therapy for idiopathic cystitis. Uncontrolled clinical trials suggest that dietary therapy designed to prevent crystalluria, such as a canned dietary therapy, may reduce the incidence of recurrent FIC episodes and urethral obstruction. Other medical therapies have been recommended to reduce struvite crystalluria in cats with idiopathic cystitis which have not been proven effective including distilled water for drinking water, salt supplementation, semi-moist cat foods or adding water to the diet, etc. Of these measures, adding water to the diet and/or feeding canned diets is the main treatment that appears to reduce recurrence of idiopathic cystitis.

A non-controlled open label clinical trial suggested that amitriptyline (5-10 mg per cat q24h) may be effective for prevention of recurrence of idiopathic cystitis; however clinical response is often minimal.26 Perineal urethrostomy (PU) has been advocated for prevention of recurrent urethral obstruction. Perineal urethrostomy may reduce the incidence of obstruction; however, it does not address the underlying disease process. Perineal urethrostomy can also predispose to ascending UTI, which can lead to infection-induced struvite urolithiasis, along with potential complications including urethral stricture. Although GAG replacement therapy (e.g., glucosamine, pentosan polysulfate) has been recommended for treatment of idiopathic cystitis, one study did not demonstrate any benefit of glucosamine over placebo-treated cats. In this study, most cats were fed more canned food during the study and both glucosamine-treated and placebo-treated cats improved to a similar degree. In a multicenter clinical trial of GAG therapy, pentosan polysulfate (Elmiron) had a small beneficial effect on cystoscopic scores in cats with idiopathic cystitis, but there was no difference in clinical signs compared to placebo. In this study and others, there was a large placebo effect that prevented any measurable benefit on clinical signs. Similarly, a placebo-controlled study of pheromone therapy also failed to demonstrate any benefit. A recent uncontrolled observational study suggested that environmental enrichment along with other behavioral modifications (termed multimodal environmental modification) resulted in significant improvement of the clinical signs of feline lower urinary tract disease and warrants further study. Environmental enrichment normalized many of the catecholamine levels and increased bladder permeability in cats with idiopathic cystitis.

Accurate client education is paramount in the management of idiopathic cystitis because of frequent recurrence and the potential life-threatening nature of urethral obstruction in male cats. Unfortunately, some client information pamphlets and many web pages about "FUS" are misleading or useless. Therefore, effective communication about the nature of idiopathic cystitis and our current understanding of treatment options are important factors that determine client adherence to recommendations.

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